Information Brochure (pdf) - Physiology and Neurobiology ...

The college of liberal arts and sciences
graduate program
application & information
Chair of Graduate Affairs
Department of Physiology and Neurobiology
75 North Eagleville Road, U-3156
Torrey Life Sciences, Rm. 67
Storrs, CT 06269-3156
Phone: (860)486-3304
Facsimile: (860)486-3303
Web: www.pnb.uconn.edu/

Introduction
Thank you for considering Graduate School and
the Department of Physiology and Neurobiology at
the University of Connecticut. This packet provides
an overview of the graduate program in physiology
and neurobiology together with brief descriptions
of individual research programs within the Department.
We recognize that your decision to pursue
an advanced degree is highly important, and we
believe that the key to choosing the right graduate
program is information. We encourage you to
learn as much as possible about our Department,
faculty, graduate students and campus. Ultimately,
a graduate education offers opportunity for intellectual
growth through learning and discovery, development
of technical and problem-solving skills and
the excitement of creativity. However, there is a
very practical aspect as well to choosing a graduate
program. Graduate school requires a major
investment of time and effort, especially to achieve
the Ph.D. This investment must be balanced
against the eventual gains in career advancement.
Our Department has an excellent record of placing
doctoral students in postdoctoral positions at very
prestigious institutions. Many now hold research
leadership positions in industry or faculty positions
in colleges and universities throughout the country.
Approximately 60% of our graduate students have
gone to college and university faculty positions
and about 30% to industrial and public service
research. This tradition of excellence stems from
a research-active faculty and a very broad curriculum
encompassing many departments. Guided
by faculty advisors, graduate students are full partners
in discovery and have considerable latitude in
designing their plans of study. Training in manuscript
writing and grant writing skills together with
opportunities to hone teaching skills and to present
findings at local and national meetings round out
our program.
-J. Larry Renfro, Ph.D.
Professor and Department Head

The University
About the Storrs Campus
The University of Connecticut at Storrs is the state's
flagship public research university. The University
has just ended the implementation of the one billion
dollar UConn 2000 program, is currently undergoing
a new 1.3 billion dollar 21st Century UConn
Program. These programs are driving a major
transformation of the University that will ensure its
place as one of the premier public research universities
in the country.
Established in 1881 as the Storrs Agricultural
College, UConn is located in northeastern Connecticut.
The University is surrounded by hiking
and biking trails, small villages, and farms. This
picturesque region dominated by rolling hills is
within two to two and one-half hours drive of the
major metropolitan areas of New York and Boston.
The University itself offers many cultural and recreational
opportunities. The newly renovated library
is now the largest public research library in New
England, and the Jorgensen Theater sponsors
numerous musical and dramatic performances
throughout the year. The new Student Recreation
Facility, and an active intramural program provide
students with ample opportunity for athletic recreation.
Gampel Pavilion, located in the heart of the
campus, is the site of exciting men's and women's
basketball.
Directions
From the West (heading through or from Hartford):
Take Interstate 84 East to Exit 68. From exit, take a
right onto Route 195, 7 miles to UConn.
From the East (heading from Boston toward
Hartford): Take Interstate 84 West to Exit 68. From exit,
take a left onto Route 195, and follow directions above.
From the Southeast Interstate 95 to 395 North.
Take Exit 81 West to Route 32 North. Follow Route 32 North
to Willimantic. In town, turn right and go over bridge. Continue
straight through the light and follow 195 North for 8
miles to campus.

Undergraduate Program
Research Experience
Within the College of Liberal Arts & Sciences we
offer several options to undergraduates. The PNB
curriculum exposes students to physiological processes
at all levels: from the interactions of individual
molecules to the behavior of the whole animal.
The most comprehensive program is the Bachelor
of Sciences in Physiology and Neurobiology.
This degree provides extensive training in Physiology
and Neurobiology in conjunction with a solid
foundation of basic sciences and the liberal arts.
Undergraduates electing to major in other fields
may concentrate on courses offered by the department
and obtain a Minor in Physiology and Neurobiology.
Our department also participates in the
interdepartmental Minor in Neuroscience. Biology
majors may also fulfill many of their course requirements
through the department of Physiology and
Neurobiology.
The Physiology and Neurobiology department is
committed to broadening the scope of undergraduate
education by adding exposure to, and involvement
in, state-of-the-art research to traditional
classroom and laboratory training. We encourage
undergraduates to become active participants in
projects being carried out in faculty research laboratories.
Independent research projects under the
supervision of faculty mentors teach many skills
and provide increased competitiveness for postgraduate
education and employment.
Projects often culminate in publications in professional
journals as well as presentations at national
and international meetings.

Graduate Program
The Graduate Research Experience
The Department of Physiology and Neurobiology
offers a program of graduate study leading to both
M.S. and Ph.D. degrees in Physiology and Neurobiology.
The program prepares students for successful
research careers in academia or industry
by providing a structured and yet flexible plan of
coursework and research. During their first year,
all students enroll in a two semester core course
where they learn the fundamental theories, facts,
and concepts necessary for advanced study in
Physiology and Neurobiology. In addition, students
are encouraged to begin original research
early in the program. First year students either
rotate through two laboratories before choosing
an area of research, or those who have already
selected a field of interest may begin dissertation
research immediately.
To complete their coursework, students choose
from several advanced courses offered within the
department in the fields of Comparative Physiology,
Endocrinology and Neuroscience. Courses
offered by other departments on campus including
Molecular and Cell Biology, Ecology and Evolutionary
Biology, Pharmacy, Biobehavioral Sciences,
and Psychology may also be taken to provide
background in other disciplines. Participation in
the departmental colloquium series and weekly
departmental meetings provides additional opportunities
for training. Through the colloquia, students
learn first hand about the newest and most exciting
research in Physiology and Neurobiology and meet
with distinguished scientists from around the world.
In the weekly departmental meetings, students
present their own original research, and refine their
presentation skills.
Progress through the program is marked by
several clearly defined accomplishments. By the
end of the first year in the program, students are
expected to have chosen a dissertation thesis laboratory,
and to have mastered the fundamentals of
neuroscience and physiology necessary for more
advanced study. This mastery is demonstrated by
performance in the core course and by passing
a comprehensive written exam. Near the end of
the second year, students write a research proposal
that is based on the original research they
have been engaged in through the first two years
in the program. After successfully defending this
proposal, students are admitted to candidacy for
the Ph.D., and/or receive an M.S. in Physiology
and Neurobiology. After admission to candidacy,
students meet regularly with their thesis advisory
committee to discuss their progress, and typically
complete their dissertation research and receive
a Ph.D. in Physiology and Neurobiology within 5
years of entering the program. All students in the
Ph.D. program receive a full tuition waiver, and a
graduate assistantship to cover living expenses.

Application Information
Undergraduate Studies
Please go to this link from the Undergraduate
Admissions office: http://admissions.uconn.edu/
content/apply to apply for undergraduate admission.
Once you have gone online and reviewed
the application process, if you have additional
questions please contact:
Undergraduate Admissions
2131 Hillside Road, Unit 3088
Storrs, CT 06269-3088
Phone: (860) 486-3137
Fax: (860) 486-1476
beahusky@uconn.edu
We encourage you to take a tour of the Storrs
campus. Depending on the day and time, you
can choose to tour the campus, meet a PNB
faculty member by appointment, attend a class,
attend a lecture, and meet current students.
Please e-mail kathleen.kelleher@uconn.edu to
arrange an appointment.
Graduate Studies
The University of Connecticut Department of
Physiology and Neurobiology confers M.S. and
Ph.D. degrees in Physiology and Neurobiology.
For more information, see http://www.pnb.
uconn.edu/PNB_Base/graduate/index.html.
You should contact a faculty member whose
research interests are most closely aligned with
your own before making a formal application.
Applications should be made directly to the
Graduate School http://www.grad.uconn.edu/
prospective/online.html. To start your self-managed
application process please begin by selecting
the appropriate checklist: Domestic & Permanent
Resident Checklist or International
Application Checklist. In addition, a personal
statement, official transcripts, and three letters of
recommendation need to be included with the finished
application, as well as a financial aid request
form (if you are eligible), and non-refundable application
fee. Your Graduate Record Examination
(GRE) scores and TOEFL scores (if English is not
your first language) must be electronically sent to
UConn (code 3915). Send all the application materials
to:
University of Connecticut
Graduate School, U-1152
438 Whitney Road Extension
Storrs, CT 06269-1152
If you have any questions about filing an application
please contact the Graduate School by phone
at 860-486-3617 or by emailing gradadmissions@
uconn.edu.

Faculty & Research
Marie E. Cantino, Associate Professor, Director of Electron Microscope Facility; Ph.D., University of
Washington (Seattle). marie.cantino@uconn.edu
William D. Chapple, Professor; Ph.D., Stanford. william.chapple@uconn.edu
Joanne Conover, Associate Professor; Ph.D., Bath University. joanne.conover@uconn.edu
Joseph F. Crivello, Professor; Ph.D., University of Wisconsin. joseph.crivello@uconn.edu
Angel de Blas, Professor, Ph. D., University of Indiana. angel.deblas@uconn.edu
Robert V. Gallo, Professor; Ph.D., Purdue. robert.gallo@uconn.edu
Alexander C. Jackson, Assistant Professor; Ph.D., Harvard University. alexander.jackson@uconn.edu
Rahul Kanadia, Assistant Professor, rahul.kanadia@uconn.edu
Joseph J. LoTurco, Professor; Ph.D., Stanford. joseph.loturco@uconn.edu
Andrew Moiseff, Professor; Ph.D., Cornell. andrew.moiseff@uconn.edu
Daniel K. Mulkey, Associate Professor; Ph. D. Wright State University. daniel.mulkey@uconn.edu
Akiko Nishiyama, Professor; M.D./Ph.D., Tokyo, Niigata (Japan). akiko.nishiyama@uconn.edu
J. Larry Renfro, Professor; Ph.D., University of Oklahoma. larry.renfro@uconn.edu
Daniel Schwartz, Assistant Professor, Ph.D., Harvard University. daniel.schwartz@uconn.edu
Jianjun Sun, Assistant Professor, Ph.D., Florida State University. jianjun.sun@uconn.edu
Anastasios V. Tzingounis, Assistant Professor; Ph.D., Vollum Institute, Oregon Health & Sciences
University. anastasios.tzingounis@uconn.edu
Randall S. Walikonis, Associate Professor; Ph.D., Mayo Clinic. randall.walikonis@uconn.edu
Affiliated Faculty
Lawrence E. Armstrong, Professor; Ph.D., Ball State, Kinesiology. lawrence.armstrong@uconn.edu
Thomas T. Chen, Professor; Ph.D., University of Alberta, Molecular & Cell Biology.
thomas.chen@uconn.edu
William J. Kraemer, Professor; Ph.D., University of Wyoming, Kinesiology. william.kraemer@uconn.edu
Carl M. Maresh, Professor; Ph.D., Wyoming, Kinesiology. carl.maresh@uconn.edu
Louise D. McCullough, Professor; M.D./Ph.D., University of Connecticut, Neurology & Neuroscience
(UConn Health Center)
Linda S. Pescatello, Professor, Director of Center for Health Promotions; Ph.D.,
University of Connecticut. linda.pescatello@uconn.edu
Steven A. Zinn, Associate Professor; Ph.D., Michigan State, Animal Science. steven.zinn@uconn.edu

Marie E. Cantino
regulation and structure of
contractile proteins
Research in my laboratory is focused on the structure
and function of contractile proteins, and the way
in which they regulate and generate force in striated
muscle. As an undergraduate at the University of
Michigan I studied physics, which seemed to explain
everything… until I took my first biology course and
discovered a world which was, at once, more frustrating
and more fascinating than that described by the
physics I knew. My graduate and postdoctoral work
in Biophysics at the University of Washington focused
on structure-function relationships in several biological
systems and made extensive use of electron
microscope-based techniques, leading to my current
position as a faculty member and director of the Electron
Microscopy Laboratory in this department.
My current research is aimed at understanding the
way calcium binding to thick and thin filaments in striated
muscle regulates and is regulated by the interaction
of actin and myosin. In vertebrate muscle, the
steep relationship between force and myoplasmic
calcium is not readily accounted for by simple binding
of calcium to troponin. Complete and rapid activation
of the contractile machinery relies on interactions with
other myofilament proteins.
Using high resolution analytical methods and image
analysis my lab is studying the distribution of calcium
binding within sarcomeres of vertebrate striated
muscle to better understand the force-calcium relationship.
This work may also help to elucidate the
molecular mechanism underlying the response of
the heart to increased myocardial load. Contractile
speed and efficiency is optimized in striated muscle
by the ordered packing of the contractile proteins.
The molecular events associated with generation of
force and movement cannot be understood without
a full description of the structural components. With
modern techniques of electron microscopy and image
analysis, we are studying the structure of sarcomeric
filaments in situ. This work is contributing to a detailed
understanding of the contractile event.

Selected Publications
Cantino, M.E., J.G. Eichen, and S.B Daniels. (1998).
Distributions of calcium in A and I bands of skinned vertebrate
muscle fibers stretched to beyond filament overlap. Biophys. J.
75:948-956.
Harford, J., M. Cantino, M. Chew, R. Denny, L. Hudson, P.
Luther, R. Mendelson, E. Morris and J. Squire. (1998). Myosin
Crossbridge configurations in equilibrium states of vertebrate
skeletal muscle: heads swing axially or turn upside down
between resting and rigor. In: Mechanism of work production
and work absorption in muscle. Eds. H. Sugi and G. Pollack.
Plenum Press, New York.
Squire, J., M. E. Cantino, M. Chew, R. Denny, J. Harford, L.
Hudson, and P. Luther. (1998). Myosin rod packing schemes in
vertebrate muscle thick filaments. Journal of Structural Biology
122:128-138.
Cantino, M. E., L. D. Brown, M. Chew, P. K. Luther and J.
M. Squire. (2000). A-band architecture in vertebrate skeletal
muscle: polarity of the myosin head array. Journal of Muscle
Research and Cell Motility 21 681-690.
Brown, L.B. and M. E. Cantino. (2001). Non-uniform distribution
of myosin light chains within the thick filaments of lobster slow
muscle: an immunocytochemical study. J. Exp. Zool. 290: 6-17.
Cantino, M. E., M. W. K. Chew, P. K. Luther, E. Morris and J. M.
Squire. (2002). Structure and Nucleotide-Dependent Changes
of Thick Filaments in Relaxed and Rigor Plaice Fin Muscle.
Journal of Structural Biology 137, 164-175.
Sun, L., L. Zhu, Q. Ge, R. P. Quirk, C. Xue, S. Z. D. Cheng,
B. S. Hsiao, C. A. Avila-Orta, I. Sics, M. E. Cantino. (2004).
Comparison of crystallization kinetics in various nanoconfined
geometries. Polymer 45: 2931-2939.
Cantino, M.E. and A. Quintanilla. (2007). Cooperative Effects
of Rigor and Cycling Crossbridges on Calcium Binding to
Troponin C. Biophys. J. 92:525-534.
Swartz, D.A., M.L. Greaser and M. E. Cantino. (2009). Muscle
Structure and Function. In Applied Muscle Biology and Meat
Science. Eds. M. Du and R.J. McCormick. CRC Press. Boca
Raton.

William Chapple
control of postural stiffness
How the central nervous system enables animals to
stand upright and maintain a stable position despite
forces tending to topple them has been an interest
of mine for many years. In mammals, signals from
mechanoreceptors are integrated with visual and
vestibular signals to stabilize an animal. This is a
complex process involving many areas of the nervous
system. I have been studying a model system for postural
control: how hermit crabs balance their shells as
they walk. Since the numbers of neurons involved in
this control are far fewer than in mammalian nervous
systems, it is possible to study this at the level of
single identified neurons.
For many years I was interested in the role of the
abdomen in the control of shell position. It acts as
a curved cantilever, the compliance of which is controlled
by the nervous system. Muscle properties and
intraganglionic interneurons and motoneurons control
this compliance by integrating signals from mechanoreceptors
beneath the abdominal surface in a feedforward
control process.

Recently, I have become interested in how the two
most posterior thoracic legs communicate with the
more anterior walking legs to control shell position.
One pair lifts the shell; the other stabilizes it in the
pitch plane. Two kinds of mechanisms might be
important in this control: signals from mechanoreceptors
in the shell support legs, and signals, (efference
copy), from the two pairs of walking. Since little
is known about walking in hermit crabs, I must first
understand how the walking legs operate. I have
been recording walking leg movement during locomotion
with a video camera, and recording emgs
from selected muscles. At the same time, I have constructed
a computer model of walking leg and shell
support movements that enables me to calculate
forces and joint torques under different experimental
conditions. Using this I will determine whether
local proprioceptive reflexes, signals from walking
leg motor centers, or both, control the action of the
two posterior thoracic appendages. I believe that by
understanding how signals between motor centers
and sensory feedback are used in this simple system,
it will be easier to understand similar processes in
more complex animals.
I received my B.A. from Harvard, and then studied
the comparative physiology of movement at Stanford
University, receiving my Ph.D. in 1965. I came to
the University of Connecticut in 1966 after post-doctoral
training at Cambridge and Bristol Universities in
England.
Selected Publications
Chapple, W.D. (1993). Dynamics of reflex co-contraction in
hermit crab abdomen: experiments and a systems model.
J.Neurophysiol. 69, 1904-1917.
Chapple, W.D. (1997). Regulation of muscle stiffness during
periodic length changes in the isolated abdomen of the hermit
crab. J.Neurophysiol. 78, 1491-1503.
Chapple, W.D. (2002). Mechanoreceptors innervating soft
cuticle in the abdomen of the hermit crab, Pagurus pollicarus.
J. Comp. Physiol. A. 188,753-766.
Chapple, W.D. and J.L. Krans. (2004) Cuticular receptor
activation of postural motoneurons in the abdomen of the
hermit crab, Pagurus pollicarus. J. Comp. Physiol. A. 190, 365-
377.
Krans, J.L. and W.D. Chapple. (2005) The action of spike
frequency adaptation in the postural motoneurons of hermit
crab abdomen during the first phase of reflex activation. J.
Comp. Physiol. A. 191, 157-174.
Krans, J.L. and W.D. Chapple. (2005) Variability of motoneuron
activation and the modulation of force production in a postural
reflex of the hermit crab abdomen. J. Comp. Physiol. A. 191,
761-775.

Joanne C. Conover
investigations into neurodegenerative
disease and the application of stem cell
and neural stem cell biology
The recent validation of the existence of stem cells in
the adult brain corroborates the nearly century-old and
largely ignored findings that neurogenesis continues
into adulthood. However, neurogenesis is restricted
to only two regions of the adult mammalian brain. The
largest, the subventricular zone, lies along the lateral
wall of the lateral ventricle and has a dual function in
supplying new neurons to the olfactory bulb and contributing
to regenerative repair within the subventricular
niche itself. We use the rodent brain as a model
system to analyze and isolate neural stem cells;
examine factors contributing to the neurogenic stem
cell niche; and investigate mechanisms of regenerative
repair.
My studies in stem cell biology began during my
postdoctoral training at the University of Pennsylvania,
where I investigated protein expression profiles
during preimplantation development when embryonic
stem cells are present. I continued work on embryonic
stem cells at Regeneron Pharmaceuticals in New
York, and combined these studies with developmental
neurobiology, focusing specifically on the role of the
cytokine CNTF and the NGF family of neurotrophic
factors in establishing the nervous system. At Rockefeller
University in NYC, I entered into the field of adult
neurogenesis. Currently, in my own laboratory at the
University of Connecticut, I continue work on embryonic
and adult stem cell biology, developmental neurobiology
and adult neurogenesis.
Our recent work focuses on three major areas of
research: (1) analysis of genes that contribute to Parkinson’s
disease through the use of in vitro embryonic
stem cell cultures; (2) examination, by functional
ablation or enhancement paradigms, of key regulatory
pathways used to support adult neurogenesis and (3)
assessment of neurogenesis and repair in the aging
or diseased brain.

Selected Publications
Conover, J.C, F. Doetsch, J.M. Garcia-Verdugo, N. W. Gale,
G.D. Yancopoulos and A. Alvarez-Buylla. (2000). Disruption
of Eph/ephrin signaling affects precursor migration and
proliferation in adult mouse brain. Nature Neurosci. 3(11):
1091-1097.
Conover, J. C. and R. L. Allen. (2002). The subventricular zone:
new molecular and cellular developments. Cell. Mol. Life Sci.
59 (12): 2128-2135.
Lennington, J.B., Z. Yang and J. C. Conover. (2003).
Neural stem cells and the regulation of adult neurogenesis.
Reproductive Biology and Endocrinology 1:99.
Luo, J, S. B. Daniels, J. B. Lennington, R, Q. Notti and J. C.
Conover. (2006). The aging neurogenic subventricular zone.
Aging Cell 5: 139-52.
Baker K. B, S. B. Daniels, J.B. Lennington, T. Lardaro,
A. Czap, R. Q. Notti, O. Cooper, O. Isacson, S. Frasca Jr.
and J. C. Conover. (2006). Neuroblast protuberances in the
subventricular zone of the regenerative MRL/MpJ mouse. J.
Comp. Neurol. 498(6): 747-761.
Conover, J. C. and R. Q. Notti. (2008). The Neural Stem Cell
Niche. Cell & Tissue Research 331(1): 211-24.
Papanikolaou, T., J. Lennington, A. Betz, C. Figuerido, J.
Salamone and J. Conover. (2008). In vitro generation of
dopaminergic neurons from adult subventricular zone neural
progenitor cells. Stem Cells and Development 17: 157-172.
Luo, J, B. A. Shook, S. B. Daniels and J. C. Conover. (2008).
Subventricular zone mediated ependyma repair in the adult
mammalian brain. J. Neurosci. 28(14): 3804-3813.
Amano, T, T. Papanikolaou, L. Sung, X. Yang and J. C. Conover.
(2009). Generation and characterization of ntES cells from
aphakia mice, a model for Parkinson¹s disease. Cloning and
Stem Cells 11: 77-88.
Papanikolaou,T., T. Amano, K. Sink, A. M. Farrar, J. Salamone,
X. Yang and J. C. Conover. (2009). Pitx3 promotes mature
mesencephalic dopamine neuron phenotype. European J.
Neurosci. 29: 2264-2275.

Joseph F. Crivello
marine toxicology and genetics
The goal of my research program is to deepen our
understanding of how marine organisms protect
themselves against the deleterious effects of anthropogenic
pollutants. Pollutants (or xenobiotics) can
have varied deleterious effects that depend on physical
(such as bioavailability), chemical, biological and
genetic factors. I focus my attention on the biochemical
and genetic effects of pollutants in marine vertebrates
and invertebrates. Part of my focus is on the protective
role of metallothionein gene expression as a function
of exposure to heavy metals (such as cadmium,
arsenic and zinc). I have examined the nonbiotic and
biotic factors that affect metallothionein gene expression
in winter flounder (Pleuronectes americanus) and
the common mummichog (Fundulus heteroclitus). We
have compared the expression of metallothionein
mRNA and protein as indicators of heavy metal exposure
and use as biomonitors of marine metal pollution.
We have cloned fragments of the metallothionein
cDNA from mummichogs and have developed QPCR
(quantitative polymerase chain reaction) technologies
for analysis of mRNA changes. We are continuing our
examination of the role of metallothionein in additional
organisms and at the level of gene expression.
I am also interested in the role of cytochrome
P450-mediated metabolism of xenobiotics in marine
vertebrates. Cytochrome P450s are a family of hemecontaining
monoxygenases involved in anabolic and
catabolic reactions of natural products (such as steroids)
as well as metabolism of pollutants to less toxic,
water-soluble forms. I am interested in two isozymes
of the P450 superfamily, CYP 1A1 and CYP 2E1,
which are responsible for the metabolism of polycyclic
aromatic hydrocarbons and small volatile organic
molecules, respectively. We have cloned cDNA for
these enzymes and are in the process of cloning the
genes for both isozymes from winter flounder. We
have looked at the expression of these activities as

a bioindicator of pollution exposure in the marine
environment. Finally, I’m interested in determining
if chronic exposure of populations of fish to low
pollutant levels induces genetic changes, i.e., is
chronic pollution a selective pressure To examine
this question, I have isolated and characterized a
number of polymorphic DNA markers that are used
to characterize genetic diversity of populations, as
well as, whether two populations are genetically
distinct.
Selected Publications
Kaplan, L.A.E., E. Fielding and J. F. Crivello. (2001). Genetic
Regulation of Liver Microsomal CYP2E1 Activity, among strains of
the viviparous fishes P. monacha and P. viriosa. Comparative
Biochemistry and Physiology 128(C): 143-152.
L. A. E. Kaplan, J. Leamon and J. F. Crivello. (2001). The
development of a rapid and sensitive, high-through-put protocol
for RNA-DNA ratio analysis. Journal of Aquatic Animal Health
13:246-256.
Ferraro, M.L, L. A. E. Kaplan, J. Leamon and J. F. Crivello.
(2001). Variations in physiological health indicators among
Fundulus heteroclitus collected from Connecticut salt
marshes. Journal Aquatic Animal Health 13:276-279.
VanCleef, K., L.A.E. Kaplan and J. F. Crivello. (2001). Killifish
metallothionein mRNA expression following temperature
perturbation and cadmium exposure. Cell Stress & Chaperones
6(4):111-121.
Ferraro, M., K. Curetsky and J. F. Crivello. (2003). The effects of
feeding restrictions on metallothionein levels and ethoxyresorufin-
O-deethylase activity in mummichogs. Journal of Aquatic Animal
Health 15:31-38.
Pelis, R., J. Goldmeyer, J. F. Crivello and J. L. Renfro. (2003).
Cortisol alters carbonic anhydrase-mediated renal sulfate
secretion. American Journal of Physiology 285(6):1430-1438.
Crivello, J. F., D. Danilla, E. Lorda, M. Keser and E. F.
Roseman. (2004). The genetic stock structure of larval and
juvenile winter flounder larvae in Connecticut waters of eastern
Long Island Sound and estimations of larval entrainment. J.
Fish Biology 65:62-76.
Crivello, J. F., D. Landers and M. Keser. (2005). The genetic
stock structure of Homarus americanus in Long Island
Sound and the Hudson Canyon. In Press, J. Shellfish Res.
Crivello, J. F., D. Landers and M. Keser. (2005). The
contribution of egg-bearing female Homarus americanus
(American lobster) populations to lobster larvae collected
in Long Island Sound by comparison of microsatellite allele
frequencies. In Press, J. Shellfish Res.
Smith, P. and J. F. Crivello. (2005). Effect of exposure to
17ß-estradiol and nonylphenol on Fundulus heteroclitus.
Submitted to J. Aquatic Toxicology.

Angel L. de Blas
gaba a receptors and gabaergic
synapses
My research centers on the study of the brain receptors
for the inhibitory neurotransmitter GABA (gamma
amino butyric acid), the molecular mechanisms
involved in GABAergic synapse formation and the
molecular organization of the postsynaptic complex
at GABAergic synapses. I have been continuously
doing research in Molecular Neurobiology since I
became a graduate student at Indiana University
where I received my Ph.D. in 1978 under the mentorship
of Professor Henry Mahler. I did my postdoctoral
training in the laboratory of the Nobel Laureate Marshall
Nirenberg at the National Institutes of Health. I
was Assistant Professor, and then Associate Professor,
in the department of Neurobiology and Behavior
at the State University of New York at Stony Brook.
Afterwards, I was appointed Professor of Molecular
Biology and Biochemistry at the University of Missouri-Kansas
City, and in 1997 I moved to the University
of Connecticut when I was appointed a professor
of Physiology and Neurobiology.
The neurotransmitter GABA inhibits neuronal activity
because it hyperpolarizes the neuron resulting from
the binding of GABA to the membrane GABA A
receptors,
which leads to the opening of the Cl - channel and
the inflow of Cl- ions inside the cell. Some psychoactive
drugs, including some anti-epileptic drugs and
sleeping pills, bind to the GABA A
receptors, facilitating
the GABA-induced Cl - channel opening. The anxiolytic,
hypnotic, anticonvulsant and muscle relaxing
properties of this class of drugs are due to their inhibition-
enhancing effect. The GABA A
receptors concentrate
at the postsynaptic membrane of GABAergic synapses.
We are studying the mechanisms that induce
GABA A
receptor clustering and anchoring at GABAergic
synapses. We are also studying why some GABA A
receptor types specifically localize at certain GABAergic
synapses while other GABA A
receptor types localize
at other GABAergic synapses or even extrasyn-

aptically. We believe that the explanation lies on
the specific interactions of these GABA A
receptor
types with anchoring proteins localized at the
GABAergic postsynaptic complex. The formation
of these postsynaptic complexes occurs at the
contact points following the innervation of neurons
by GABAergic presynaptic terminals. We are also
trying to identify endogenous brain substances
that might function as substances present in the
brain that act as natural anxiolytic and relaxing
substances.
Selected Publications
Christie, S.B., Miralles, C.P. and De Blas, A.L.: GABAergic
Innervation Organizes Synaptic and Extrasynaptic GABA A
Receptor Clustering in Cultured Hippocampal Neurons. J.
Neurosci. 22:684-697, 2002.
Riquelme, R., Miralles, C.P. and De Blas, A.L.: Bergmann glia
GABA A
Receptors Concentrate on the Glial Processes that Wrap
Inhibitory Synapses. J. Neurosci. 22:10720-10730, 2002.
Christie, S.B. and De Blas, A.L.: GABAergic and Glutamatergic
Axons Innervate the Axon Initial Segment and Organize GABA A
Receptor Clusters of Cultured Hippocampal Pyramidal Cells. J.
Comp. Neurol. 456:361-374, 2003.
Charych, E., Yu, W., Miralles, C.P., Serwanski, D.R., Li, X.,
Rubio, M., and De Blas, A.L.: The Brefeldin A-inhibited GDP/GTP
Exchange factor 2, a Protein Involved in Vesicular Trafficking,
Interacts with the ß Subunits of the GABA A
Receptors. J.
Neurochem. 90:173-189, 2004.
Charych, E., Yu, W., Li, R.W., Serwanski, D.R., Miralles, C.P.,
Li, X., Yang, B-W., Pinal, N., Walikonis, R., and De Blas, A.L.:
A four PDZ-Domain Containing Splice Variant Form of GRIP1 is
localized in GABAergic and Glutamatergic Synapses in the Brain.
J. Biol. Chem. 279:38978-38990, 2004.
Li, R.-W., Serwanski, D.R., Miralles, C.P., Li, X., Charych, E.,
Riquelme, R., Huganir, R.L., and De Blas, A.L.: GRIP1 in
GABAergic Synapses. J. Comp. Neurol. 488:11-27, 2005
Li, R-W, Yu, W., Christie, S.B., Miralles, C.P., Bai, J., LoTurco,
J.J., and De Blas, A.L.: Disruption of GABAA Receptor Clusters
Leads to Decreased GABAergic Innervation of Pyramidal
Neurons. J. Neurochem: 95:756-770, 2005.
Serwanski, D.R., Miralles, C.P., Christie, S.B., Mehta, A.K., Li,
X., and De Blas, A.L.: Synaptic and non-synaptic localization
of GABAA receptors containing the α5 subunit in the rat brain.
J. Comp. Neurol. 499:458-470, 2006.
Li, X., Serwanski, D.R., Miralles, C.P., Bahr, B.A., and De Blas,
A.L.: Two pools of Triton X-100-insoluble GABA A
receptors are
present on the brain, one associated to lipid rafts and another
one to the postsynaptic GABAergic complex. J. Neurochem.
102:1329-1345, 2007.
Rissman RA, De Blas AL, Armstrong DM. GABA(A) receptors in
aging and Alzheimer’s disease. J Neurochem.103:1285-1292,
2007.
Yu, W., Jiang, M., Miralles, C.P., Li, R.W., Chen G., and De
Blas, A.L.: Gephyrin clustering is required for the stability of
GABAergic synapses. Mol. Cell. Neurosci. 36:484-500, 2007.
Yu, W., Charych, E.I., Serwanski, D.R., Li, R,W,, Ali, R., Bahr,
B.A., and De Blas, A.L.: Gephyrin interacts with the glutamate
receptor interacting protein 1 isoforms at GABAergic
synapses. J Neurochem. 105:2300–2314, 2008.
Yu, W. and De Blas, A.L.: Gephyrin expression and clustering
affects the size of glutamatergic synaptic contacts. J.
Neurochem. 104:830-845, 2008.
Li, X., Serwanski, D.R., Miralles CP., Nagata K., and De
Blas, A.L.: Septin 11 is present in GABAergic synapses and
plays a functional role in the cytoarchitecture of neurons and
GABAergic synaptic connectivity. J. Biol. Chem. 284:17253-
17265, 2009.
Christie, S.B., Li R.W., Miralles C.P., Yang, B.-Y. and De Blas,
A.L.: Clustered and non-Clustered GABA A
Receptors in cultured
Hippocampal Neurons. Mol. Cell. Neurosci. 31:1-14, 2006.

Robert V. Gallo
Our current research is to investigate the involvement
of endogenous opioid peptides in regulating the
surge of LH release that causes ovulation. A concept
has been developed in the literature that a decrease
in the inhibitory influence of endogenous opioid peptides
on LH secretion on the afternoon of proestrus in
the rat estrous cycle is an important event contributneuroendocrine
regulation of
luteinizing hormone release
The overall goal of my research is to understand the
neuroendocrine mechanisms regulating luteinizing
hormone (LH) release from the anterior pituitary. I
became interested in this subject in graduate school,
working in the laboratory of M.X. Zarrow at Purdue University,
where I received my Ph.D. in 1968. I then spent
two years of postdoctoral study at the UCLA Brain
Research Institute with C.H. Sawyer. My first faculty
position was at the UCSF School of Medicine in the
Department of Physiology from 1970-1982. In 1982 I
joined the faculty at the University of Connecticut.

ing to the occurrence of the ovulatory LH surge.
This suppression is postulated to be exerted by
b-endorphin originating in arcuate nucleus neurons
and acting via mu-opioid receptors. However, the
potential involvement of other opioid peptides and
their receptors in “disinhibition” of the LH surge
remained to be explored.
Recent work in my laboratory suggested that a
reduction in medial preoptic area (MPOA) kappaopioid
receptor-mediated inhibitory tone may also
be a critical event in generation of the LH surge, as
pharmacological blockade of kappa-opioid receptors
with norbinaltorphimine at this CNS site late on
the morning of proestrus prematurely advanced the
ovulatory LH surge. Dynorphin is the endogenous
ligand for the kappa-opioid receptor, and very little
is known about the role of the prodynorphin family
of endogenous opioid peptides in reproductive neuroendocrine
function. Additional studies demonstrated
that prodynorphin-derived peptides, acting
through kappa-opioid receptors, block the LH surge
and ovulation. Dynorphin A1-17 and A1-8 are the
most potent in this regard. Neutralization of these
peptides, by push-pull perfusion of the MPOA on
the morning of proestrus with antibodies (Ab) specific
for each peptide, resulted in some animals in
an advancement in the time of LH release sufficient
to cause ovulation. This suggested that these two
peptides might have a role in the MPOA, although
a minor one, in suppressing LH secretion early
on proestrus. A reduction in prodynorphin gene
expression on the afternoon of proestrus may be
one event involved in a possible decrease in dynorphin
inhibitory tone on the ovulatory LH surge-generating
signal. However, a complete loss of kappaopioid
inhibition is not required for the onset of the
LH surge. These experiments have broadened our
understanding of the role of the prodynorphin family
of opioid peptides in reproductive neuroendocrine
function by clarifying their role in the mechanisms
regulating the ovulatory LH surge.
Selected Publications
Smith, M.J., and R.V. Gallo. (1997). The effect of blockade
of kappa-opioid receptors in the medial preoptic area on the
luteinizing hormone surge in the proestrous rat. Brain Research
768: 111-119.
Zhang, Q., and R.V. Gallo. (2002). Effect of prodynorphinderived
opioid peptides on the ovulatory luteinizing hormone
surge in the proestrous rat. Endocrine 18: 27-32.
Zhang, Q., J. M. McCoy, and R. V. Gallo. (2002). Further studies
on possible dynorphin involvement in the ovulatory luteinizing
hormone surge in the proestrous rat. Endocrine 18: 231-238.
Zhang, Q., and R. V. Gallo. (2003). Presence of kappa-opioid
inhibitory tone at the onset of the ovulatory luteinizing hormone
surge in the proestrous rat. Brain Research 980: 135-139.

Alexander C. Jackson
CELLULAR AND SYNAPTIC
NEUROPHYSIOLOGY OF
HYPOTHALAMIC NEURAL CIRCUITS
The state of our mental and physical health is intimately
intertwined with daily rhythms in sleep, wakefulness
and feeding. Disruptions in sleep architecture,
energy balance and neuroendocrine homeostasis are
pathophysiological features of major neuropsychiatric
and neurological diseases, obesity and diabetes. This
strong association is suggestive of common mechanisms
at the level of neuromodulatory circuits and transmitter
systems. Many of the circuits that govern such
crucial physiological functions are found in the hypothalamus
- a region of the brain characterized by both rich
interconnectivity with other brain regions and the ability
to integrate a variety of humoral signals from the periphery.
The overall goal of research in my laboratory is to
advance our understanding of the cellular and synaptic
mechanisms through which specific neural circuits in the
mammalian hypothalamus regulate behavior.
I first became fascinated with neuromodulatory circuits
in the hypothalamus as physiology major at McGill
University, where I carried out research on neuropeptide
receptors at the Montreal Neurological Institute. I
subsequently pursued my doctoral work with Dr. Bruce
Bean at Harvard Medical School, where I used patchclamp
electrophysiology and pharmacology to study
the properties of subtheshold ionic currents that underlie
the electrical activity characteristic of two populations
of hypothalamic pacemaker neurons, essential
for driving sleep-wake rhythms. Following my PhD, I
pursued further training in neurophysiology as a postdoctoral
fellow with Dr. Roger Nicoll at the University of
California, San Francisco (UCSF). Early in my postdoctoral
work, my research focused on the role of auxiliary
subunits in AMPA receptor-mediated synaptic transmission,
plasticity and pharmacology in cerebellar interneurons.
Later in my postdoctoral work, I applied my training
in cellular and synaptic physiology to questions in the
hypothalamus by establishing a collaboration with Dr.
Luis de Lecea of Stanford University. Through this collaboration,
I studied neurotransmission in hypothalamic
neural circuits while acquiring further training in in vivo
optogenetics, electroencephalographic (EEG) recording
and neuroanatomical methods. Collectively, my training
has provided the foundation for ongoing work in my own
19
laboratory.

Selected Publications:
Jackson AC and Nicoll RA. (2011) Stargazing from a new
vantage - TARP modulation of AMPA receptor pharmacology
(Perspective). Journal of Physiology. 589: 5909-5910
Jackson AC and Nicoll RA. (2011) The Expanding Social
Network of Ionotropic Glutamate Receptors: TARPs and Other
Transmembrane Auxiliary Subunits. (Review) Neuron. 70: 178-
199.
Jackson AC*, Milstein AD*, Soto D*, Farrant M, Cull-Candy
SG and Nicoll RA. (2011) Probing TARP modulation of AMPA
receptor conductance with polyamine toxins. Journal of
Neuroscience. 31: 7511-7520. *Equal contribution
Cavanaugh DJ*, Chesler A*, Jackson AC, Sigal YM, Yamanaka
H, Grant R, O’Donnell D, Nicoll RA, Shah N, Julius D, Basbaum,
AI. (2011) Trpv1 reporter mice reveal highly restricted brain
distribution and functional expression in arteriolar smooth muscle
cells. Journal of Neuroscience. 31: 5067-5077.
*Equal contribution
Jackson AC and Nicoll RA. (2011) Stargazin (TARP gamma-2)
is required for compartment-specific AMPA receptor trafficking
and synaptic plasticity in cerebellar stellate cells. Journal of
Neuroscience. 31: 3939-3952.
I joined the faculty of the Department of Physiology
and Neurobiology at the University of Connecticut
in September, 2013. Research in my laboratory
is focused on understanding how two interrelated
hypothalamic neural circuits operate at the cellular,
synaptic and circuit levels. One is the hypocretin/orexin
(Hcrt/Ox) system in the lateral hypothalamic
area (LHA) - a linchpin in the regulation
of arousal, reward and energy balance. Hcrt/Ox
neurons have been implicated in the stabilization of
sleep-wake states and their dysfunction has been
directly linked to human narcolepsy. Second is the
histaminergic (HA) system in the tuberomammillary
nucleus (TMN), which extends fibers throughout
the CNS and is well positioned to drive transitions
between global brain states and influence
attention and cognition. Despite advances in our
understanding of these systems, the fundamental
mechanisms underlying their function are poorly
understood at the cellular and systems level. This
gap is largely attributable to the heterogeneous,
complex and sparsely distributed nature of hypothalamic
neural circuits and the challenge of selectively
manipulating specific neuronal populations.
In order to overcome these technical obstacles in
studying hypothalamic circuits, I am taking a multidisciplinary
approach. Techniques are centered
on using patch-clamp electrophysiology and pharmacology
in brain slices from transgenic mice in
order to elucidate the cellular and synaptic properties
of specific hypothalamic cell-types and their
local and long-range connectivity. This approach
is carried out in concert with a toolbox of neuroanatomical
methods and optogenetic and pharmacogenetic
strategies to manipulate the excitability
of genetically targeted neurons, both in brain
slices and in awake and behaving animals. My
long-term research goal is to elucidate the cellular,
synaptic and circuit-level mechanisms through
which the Hcrt/Ox and HA systems, and interconnected
hypothalamic neuromodulatory circuits,
regulate fundamental behavioral states such as
sleep, wakefulness and energy balance, in health
and disease.
Lu W, Shi Y, Jackson AC, Bjorgan K, During MJ, Sprengel
R, Seeburg PH and Nicoll RA. (2009) Subunit composition
of synaptic AMPA receptors revealed by a single-cell genetic
approach. Neuron. 62: 254-268.
Jackson AC and Bean BP. (2007) State-dependent
enhancement of subthreshold A-type potassium current by
4-aminopyridine in tuberomammillary nucleus neurons. Journal
of Neuroscience. 27: 10785-10796.
Jackson AC, Yao GL and Bean BP. (2004) Mechanism of
spontaneous firing in dorsomedial suprachiasmatic nucleus
neurons. Journal of Neuroscience. 24: 7985-7998.
Roseberry AC, Liu HY, Jackson AC, Cai X and Friedman
JM. (2004) Neuropeptide Y-mediated inhibition of
proopiomelanocortin neurons in the arcuate nucleus shows
enhanced desensitization in ob/ob mice. Neuron. 41: 711-722.
Beaudet A, Jackson AC, and Vandenbulcke F. (2002)
Confocal and Electron Microscopic Tracking of Internalized
Neuropeptides and/or their Receptors. (Book Chapter) in A.
Merighi and G. Carmignoto (Editors), Cellular and Molecular
Methods in Neuroscience Research. Springer-Verlag New
York, Inc., 15-28

Rahul N. Kanadia
alternative splicing &
neuronal development
We are interested in the role of posttranscriptional
gene regulation during vertebrate development.
Specifically, we want to understand the
role of alternative splicing, which has recently
gained more attention since it was discovered that
the human genome has fewer, 23,425, protein
coding genes. This observation was quite surprising
when one considers that some of the invertebrate
species such as the Drosophila (Fruit fly)
has 14,000 protein coding genes. Thus, with an
additional 10,000 genes one can make an entire
human being. This raises the question as to how
humans acquire the vast proteome complexity
needed to build such a complex organism from so
few genes. It is here that alternative splicing plays
a vital role. Alternative splicing facilitates combinatorial
splicing of exons to produce multiple protein
isoforms from a single gene. Indeed, most vertebrate
genes are now known to be alternatively
spliced. Given the extent to which the genes are
alternatively spliced, we want to understand how
alternative splicing is regulated during development
and the impact it may have in regulating
gene networks during development.

We employ mouse (mus musculus) as the primary
model organism for our investigations. Moreover,
it has been reported that amongst all the tissues,
the central nervous system has the highest amount
alternatively spliced transcripts. Thus, we employ
the neural retinal to elucidate the role of Alternative
Splicing in neural development.
Our current work has focused on the role of alternative
splicing in regulating bHLH transcription
factors during retinal development. Specifically,
we have investigated the post-transcriptional regulation
of one of the atonal homologues called
Math5. We have found that this gene is a single
exon gene, which is alternatively spliced to produce
two isoforms. Interestingly, the major isoform is
spliced such that the entire coding sequence is
spliced out. Consequently, most of the RNA that
is produced for Math5 cannot produce a functional
protein. This raises several interesting questions,
which will be the focus of our future investigations.
First, why should retinal progenitor cells produce
Math5-mRNA that does not code for protein
Second, does the non-coding isoform of Math5
have a function Third, is this form of regulation
found in other bHLH transcription factors
Selected Publications
Kanadia, R. N. and C. L Cepko. (2010). Alternative splicing
produces high levels of noncoding isoforms of bHLH transcription
factors during development. Genes and Development 24(3):
229-34
Kanadia,R. N., V. E. Clark, C. Punzo, J. Trimarchi and C. Cepko.
(2008). Temporal requirement of the alternative splicing factor
Sfrs1 for the survival of retinal neurons. Development 135(23):
3923-33.
Kanadia, R. N., J. Shin, Y. Yuan, S. G. Beattie, T. Wheeler, C.
A. Thornton and M. S. Swanson. (2006). Reversal of RNA missplicing
and myotonia following muscleblind overexpression in a
mouse poly(CUG) model for myotonic dystrophy. Proceedings of
the National Academy of Sciences, USA. August 1st; 103 (31):
11748-53.
Kanadia R. N., K. A. Johnstone, A. Mankodi, C. Lungu, C.
A. Thornton, D. Esson D, Timmers, W. W. Hauswirth, M. S.
Swanson. (2003). A muscleblind knockout model for myotonic
dystrophy. Science 302(5652): 1978-80
Kanadia, R. N., Y. Yuan, M. G. Poulos and M. Swanson.
(2005). Journal of Biomolecular Structure and Dynamics, Book
of Abstract Albany 22(6)
Lin, X., J.W. Miller, A. Mankodi, R. N. Kanadia, Y. Yuan, R.
T. Moxley, M. S. Swanson, C. A. Thornton. (2006). Failure of
MBNL1-dependent postnatal splicing transitions in myotonic
dystrophy. Human Molecular Genetics 15 (13): 2087-97.
Y. Yuan, R. N. Kanadia, M. S. Swanson. (2005). Impact
of Unstable Microsatellites on RNA processing (Review).
CHEMTRACTS Biochemistry and Molecular Biology 18(3):
129-140.
Kanadia, R. N., C. R. Urbinati, V. J. Crusselle, D. Luo, Y. J. Lee,
J. K. Harrison, S. P. Oh, M.S. Swanson. (2003). Developmental
expression of mouse muscleblind genes Mbnl1, Mbnl2 and
Mbnl3. Gene Expr Patterns 3(4): 459-62.

Joseph J. LoTurco
neocortical development and
function
The research goals in my laboratory are to i) define the
cellular and molecular signals that promote and regulate
the generation and migration of neurons within
the neocortex, ii) understand why certain disruptions
in normal neocortical development cause epilepsy,
and learning disorders, and iii) understand how production
of new neurons in the mature brain may be
used to repair damaged neuronal circuits. Our experiments
make use of multiple approaches and technologies
including retrovirus-mediated gene-transfer,
in utero gene transfer, siRNA, confocal microscopy,
patch-clamp electrophysiology and immunocytochemistry.
With this combination of approaches we strive to
unravel how the most sophisticated computing device
in nature is constructed, how its malformation leads to
neurological disease, and how we might repair it in the
future through triggered neuronal replacement.
I completed my Ph.D. in Neurosciences at Stanford
University in 1991, where I used patch-clamp techniques
to define the neurotransmitter receptors and
ion channels that mediate interactions in the earliest
phases of neocortical development. I then went to the
Department of Genetics at Harvard Medical School
for my post-doctoral studies, where I continued work
on defining signaling systems that promote the differentiation
of neuronal progenitors and gained training
in molecular genetic technologies. I have had my own
lab at the University of Connecticut since 1994.
Our recent work has focused on determining how
the neurons that populate the mature neocortex are
generated and migrate to form functional layers. We
have focused our efforts on a set of genes that when
mutated in humans or rodents lead to malformations
that clearly indicate their critical role in either neuronal
production or migration. Two genes of particular
interest are Citron-kinase, essential to neurogenic cell
division, and doublecortin, essential to radial migration.
We are now identifying the specific cellular functions
controlled by these proteins, and identifying the
proteins that interact with them.
23

Selected Publications
Bai, J., et al. (2003). RNAi reveals doublecortin is required for
radial migration in rat neocortex. Nat Neurosci. 6(12): 1277-83.
Meng, H., et al. (2005). DCDC2 is associated with reading
disability and modulates neuronal development in the brain. Proc
Natl Acad Sci USA 102(47): 17053-8.
Ramos, R.L., J. Bai, and J.J. LoTurco. (2006). Heterotopia
Formation in Rat but Not Mouse Neocortex after RNA
Interference Knockdown of DCX. Cereb Cortex.
Paracchini, S., et al. (2006). The chromosome 6p22 haplotype
associated with dyslexia reduces the expression of KIAA0319,
a novel gene involved in neuronal migration. Hum Mol Genet,
2006. 15(10): 1659-66.
LoTurco, J.J. and J. Bai. (2006). The multipolar mode and
neuronal migration disorders. Trends in Neuroscience 27(7):
407.
Ackman, J., R. L. Ramos, M. R. Sarkisian, and J. J. LoTurco.
(2007). Citron Kinase is Required for Postnatal Neurogenesis in
the Hippocampus. Dev Neurosci. 29(1-2): 113-23.
Galaburda, A. M., J. J. LoTurco, F. Ramus, R. H. Fitch, G.
D. Rosen. (2006). From genes to behavior in developmental
dyslexia. Nat Neurosci. 9(10):1213-7.
Ackman, J. B., F. Siddiqi, R. S. Walikonis, LoTurco J. J. (2006).
Fusion of microglia with pyramidal neurons after retroviral
infection. J Neurosci. 26(44):11413-22.
Wang, Y., M. Paramasivam, A. Thomas, J. Bai, N. Kaminen-
Ahola, J. Kere, J. Voskuil, G. D. Rosen, A. M. Galaburda, J. J.
LoTurco. (2006). DYX1C1 functions in neuronal migration in
developing neocortex. Neuroscience 143(2):515-22.
Paramasivam, M., Y. J. Chang, and J. J. LoTurco. (2007). ASPM
and Citron Kinase Co-Localize to the Midbody Ring During
Cytokinesis. Cell Cycle 6(13).
Bai J., R. L. Ramos, M. Paramasivam, F. Siddiqi, J. B. Ackman,
J. J. LoTurco. (2008). The role of DCX and LIS1 in migration
through the lateral cortical stream of developing forebrain. Dev
Neurosci. 30(1-3):144-56.
Manent, J. B., Y. Wang, Y. J. Chang, M. Parmasivam and J. J.
LoTurco. (2009). Dcx reexpression reduces subcortical band
heterotopia and seizure threshold in an animal model of neuronal
migration disorder. Nature Medicine 15 (1) 84-90.
Loturco, J. J., J. B. Manent, F. Siddiqi. (2009). New and
Improved Tools for In Utero Electroporation Studies of
Developing Cerebral Cortex. Cerebral Cortex.

Andrew Moiseff
sensory neuroethology
I consider myself to be a neuroethologist. In particular,
I am interested in sensory neurophysiology and
how it relates to an animal's ability to interact with
its environment in a biologically meaningful way.
I enjoy approaching this problem using a variety of
techniques that include electrophysiology, computer
modeling and simulation, behavior and molecular
biology. My exposure to neuroethology began when
I was an undergraduate at SUNY Stony Brook learning
electrophysiology on cockroaches and behavior
on fireflies. As a graduate student at Cornell I studied
auditory interneurones in the cricket under the mentorship
of Dr. Ronald R. Hoy. I was able to correlate
the response properties of an ultrasound-sensitive
identified neuron to a behavioral escape-response.
My postdoctoral work was carried out with Dr. Mark
Konishi, at Caltech. There, I investigated the auditory
pathways that processed the binaural cues that the
owl relied on to localize sounds.
One project has been the study of communication in
fireflies. These insects use flashes of light to communicate
between individuals. Information about species
and sex is encoded in the flash timing and pattern.
Information about the individual that may be important
for mate selection may also be present in the
flash signal. The goal is understand how the firefly
nervous system extracts behaviorally relevant information
from these flashes of light. Clues to nature of
the information transmitted by flashing are revealed
through behavioral studies of fireflies in their natural
environment. Using low-light videography and sensitive
photodetectors male and female activity can be

described and details of the flashes can be measured
with precision. Hypotheses about the function
of flashes are tested in the field or in the
laboratory by experimentally manipulating flash
parameters. We custom design and build microprocessor-based
systems that use light emitting
diodes to produce flashes of light under experimenter
control. The diodes are programmed to
simulate the flash behavior of male or female
fireflies. By systematically varying specific flash
parameters and measuring the effects on the
interaction between the simulated firefly and a real
firefly we determine how information is coded in
the flash signals. As flash features are identified
behavioral, morphological, neuroanatomical, electrophysiological
techniques are used to investigate
how the flashes are detected, encoded and
processed by the firefly brain. The strategies and
neural processing employed by fireflies for their
specialized form of communication may serve as
a foundation for understanding neural processing
in other species including humans.
Selected Publications
A. Moiseff and J. Copeland (2000). The occurrence of a
new type of synchrony in a North American firefly. J Insect
Behavior 13: 597-612.
Leamon, J., A. Moiseff and J. Crivello. (2000). Development
of a high-throughput process for detection and screening of
genetic polymorphisms. Biotechniques 28: 994-1005.
Moiseff, A., J. Copeland, L. Faust, and F. Kubke. (2002).
Female flashes in a synchronic North American rover firefly.
Society for Integrative and comparative Biology, Abstracts.
Newsome, B., J. Copeland and A. Moiseff. (2002). Synchrony
and flash inhibition in a North American firefly. Society for
Integrative and comparative Biology, Abstracts.
Copeland, J. and A. Moiseff. (2002). Synchronic flashing in
a North American firefly. Integrative and Comparative Biology
42: 121.
Pytte, C. L., M. S. Ficken and A. Moiseff. (2004). Ultrasonic
singing by the blue-throated hummingbird: A comparison
between production and perception. J. Comp Physiol. 190(8):
665-673.
Kim, D., D. Schneider and A. Moiseff. (2005). ARO Abstracts,
p.334.
Ramos R., A. Moiseff and J. Brumberg. (2007). Utility and
Versatility of Extracellular Recordings from the Cockroach for
Neurophysiological Instruction and Demonstration. Journal of
Undergraduate Neuroscience Education 5:A28-A34.
Copeland J, A. Moiseff, L. Faust. (2008). Landing distance in
a synchronic North American firefly. Physiol Ent 33:110-115
Kim, D. O., A. Moiseff, J. B. Turner, J. Gull. (2008). Acoustic
cues underlying auditory distance in barn owls. Acta Oto-
Laryngol 128:382-387
Copeland, J. and A. Moiseff. (2004). Flash Entrainment in
Two Synchronic Firefly Species. J. Ent. Sci. 39: 151-158.
Copeland, J. and A. Moiseff. (2004). Flash precision at the
start of synchrony in Photoris frontalis. Integ. and Comp. Biol.
44:259-263.

Daniel K. Mulkey
cellular and molecular
mechanisms by which the brain
controls breathing
Breathing is essential for life. It provides the means to
obtain the O 2
necessary for aerobic metabolism and
to eliminate the CO 2
produced as a metabolic byproduct.
In addition, via its effects on CO 2
levels, breathing
serves a second critical function: rapid and dynamic
regulation of acid-base balance. The importance of
this latter function is underscored by the existence of
an exquisitely sensitive homeostatic mechanism – socalled
respiratory chemoreception – by which the rate
and depth of breathing are controlled by arterial CO 2
/
pH.
The focus of my research is centered on the electrophysiological
characteristics of mammalian neurons in
brainstem regions associated with respiratory control,
specifically defining properties unique to respiratory
chemoreceptors. I am also interested in the cellular
mechanisms by which chemoreceptors sense
changes in CO 2
/pH.
I first became interested in central chemoreception
as a graduate student at Wright State University. As
part of my thesis I showed that CO 2
-sensitive neurons
in the solitary complex, a cardio-respiratory integration
center, also respond to oxidative stress by a free
radical dependent and pH independent mechanism.
Later as a postdoctoral fellow in the laboratories of
Douglas Bayliss and Patrice Guyenet at the University
of Virginia I helped identify a population of neurons
on the surface of the brainstem in a region called the
retrotrapezoid nucleus (RTN) that appear to function
as chemoreceptors. These neurons are highly CO 2
-
sensitive in vivo (whole animal), intrinsically pH-sensitive
in vitro (brain slice), are glutamatergic and send
excitatory projections to the respiratory rhythm generator.
We also determined that RTN chemoreceptors
express an as of yet unidentified pH sensitive voltage
independent K + current tha t likely confers pH sensitivity
to these cells (see corresponding figure). Little
else is known regarding the properties of cells in this
region of the brainstem.

I joined this department in August of 2007 where I
have continued to investigate the role of the RTN
in respiratory control. We are currently using patch
clamp techniques in brain slices to identify morphological
and electrical properties that distinguish
RTN chemoreceptors from non-chemosensitive
neurons. In addition, it is well known that glial cells
can modulate neuronal activity through control of
the extracellular environment (e.g., pH buffering)
or by releasing neurotransmitters. Therefore, we
are using immunohistochemistry to identify the
types of glial cells present in the RTN as well as
a combination of pharmacological, electrophysi-
ological and fluorescent imaging (e.g., Ca 2
+
and
intracellular pH and ATP) techniques to determine
if glial cells modulate activity of RTN chemoreceptors.
Finally, my earlier finding that free radicals
affect CO 2
sensitive neurons in a cardio-respiratory
region of the brain suggests that multiple signaling
molecules can affect the output of chemoreceptors
and consequently contribute to the drive
for breathing. Therefore, we are investigating the
mechanism by which nitric oxide, a neuromodulator
released during sleep, contributes to the state
dependent control of breathing.
Selected Publications
Mulkey, D. K, R. A. Henderson III, N.A. Ritucci, R. W. Putnam, J.
B. Dean. (2004). Oxidative stress decreases intracellular pH and
Na + /H + exchange and increases excitability of solitary complex
(SC) neurons from rat brain slices. Am J Phyiol Cell Physiol
286:C940-C051, .
Mulkey D. K., M. C. Weston, R. L. Stornetta, A. Parker, D. A.
Bayliss, P. G. Guyenet. (2004). Respiratory control by ventral
surface chemoreceptor neurons in rat. Nature Neurosci. 7:1360-
1369.
Mulkey D. K., E. M. Talley, R. L. Stornetta, A. R. Siegel, G. H.
West, N. Sen, M. M. Akshitkumar, P. G. Guyenet, D. A. Bayliss.
(2007). TASK channels determine pH sensitivity in select
respiratory neurons but do not contribute to central respiratory
chemosensitivity. J Neurosci 27:14049-14058.
Mulkey D. K., D. L. Rosin, G. H. West, A. C. Takakura, T. S.
Moreira, D. A. Bayliss, P. G. Guyenet. (2007). Serotonergic
neurons activate chemosensitive RTN neurons by a
pH-independent mechanism. J Neurosci 27:14128-14138.
Mulkey D. K., A. M. Mistry, P. G. Guyenet, D. A. Bayliss. (2006).
Purinergic P2 receptors modulate excitability but do not mediate
pH-sensitivity of RTN respiratory chemoreceptors. J Neurosci.
26:2730-2733.

Akiko Nishiyama
glial cell biology
I am interested in understanding how different cell
types in the mammalian central nervous system
(CNS) interact with each other. I have been studying
a population of glial cells in the rodent CNS which
can be identified by the expression of the NG2 proteoglycan.
During development NG2 glial cells give
rise to oligodendrocytes, which make myelin sheaths
around axons. However, not all NG2 cells differentiate
into oligodendrocytes, and a large number of NG2
glial progenitor cells persist in the mature CNS (see
Figure).
I first became aware of the importance of glial cells
while I was a resident in neuropathology and was
examining brain tissues from patients who had died
of various neurodegenerative diseases. I learned that
although nervous system dysfunction usually occurs
as a result of neuronal damage, glial cells are the first
cells to react to most types of injury, long before morphological
changes in neurons become apparent. I
wanted to be able to analyze the cellular responses to
injury at the molecular level, beyond the morphological
studies routinely carried out in a pathology laboratory,
and received my graduate training in Molecular
Neuropathology / Neurobiology at the Brain
Research Institute in Niigata, Japan. While studying
gene expression in different glial cell lines, I became
interested in the heterogeneity of glial cells.
This led me to seek postdoctoral training at the La
Jolla Cancer Research Foundation with Bill Stallcup,
who had just reported that the NG2 proteoglycan is
expressed on a subpopulation of glial progenitor cells.
While determining the primary structure and some
biochemical properties of the rat NG2 proteoglycan as
a part of a group studying cell adhesion molecules in
development, I developed an interest in how extracellular
and cell surface molecules play a role in regulating
cell proliferation, migration, and differentiation.
During the second half of my postdoctoral period, I
studied the distribution of NG2 cells in the CNS and
found that numerous NG2 cells exist not only in the
developing brain but also in the mature brain. This
observation led to the question of whether the NG2
cells in the adult CNS are a source of remyelinating
cells in demyelinating lesions, which I pursued at the

Cleveland Clinic, where I was a part of a group
studying various aspects of the demyelinating
disease, multiple sclerosis.
I joined this department in 1998. We are currently
using the following approaches to study what NG2
cells do and how their proliferation and differentiation
are regulated. 1) Use primary cultures of
neurons and different glial cells to study the effects
of glial cells on neuronal functions. 2) Study the
interaction between NG2 cells and axons. 3)
Study molecular mechanisms of NG2 cell proliferation
and differentiation in dysmyelinating mutant
mice and demyelinating lesions. 4) Use the BAC
transgenic approach to target the expression of
various genes to NG2 cells in transgenic mice to
study the physiological functions of NG2 cells. 5)
Use newly generated transgenic mouse lines to
trace the fate of NG2 cells and examine whether
NG2 cells can function as stem cells.
Selected Publications
Yang, Z., R. Suzuki, S. B. Daniels, C. B. Brunquell, C. J. Sala,
A. Nishiyama. (2006). NG2 glial cells provide a favorable
substrate for growing axons. J Neurosci. 26(14):3829-39,
2006. (featured in Journal Club: Barbara Lober. Role of NG2 in
Development and Regeneration. J Neurosci. 26(27):7127-7128,
2006.)
Ziskin J. L., A. Nishiyama, M. Fukuya, M. E. Rubio, D.
E. Bergles. (2007). Vesicular release of glutamate from
unmyelinated axons in white matter. Nature Neuroscience
10(3):321-30.
Zhu, X., D. E. Bergles, A. Nishiyama. (2008). NG2 glial cells
generate both oligodendrocytes and astrocytes. Development
135(1):145-57.
Komitova, M., X. Zhu, D. R. Serwanski, and A. Nishiyama.
(2009). NG2 cells are distinct from neurogenic cells in the
subventricular zone. J Comp Neurol 512:702-715.
Nishiyama, A., M. Komitova, R. Suzuki, X. Zhu. (2009). NG2
cells (polydendrocytes): multifunctional cells with lineage
plasticity. Nature Rev Neurosci 10:9-22.

J. Larry Renfro
Mechanisms and regulation of
epithelial transport
Perturbations of the composition of the vertebrate
internal milieu may provoke homeostatically appropriate
responses either indirectly through hormonal
and neural pathways or directly through physicochemical
interactions with cellular membrane transport
systems. My interests have centered on the processes
of epithelial ion transport and their modulation.
Current ongoing studies in the lab deal with the mechanisms
and control of uric acid and inorganic phosphate
transport.
My interests in osmoregulation and responses of
physiological systems to stress began in the desertlike
regions of southern Oklahoma and the panhandle
of Texas. This work led me, as a post-doctoral fellow,
to the laboratory of Bodil Schmidt-Nielsen at Case
Western Reserve University and, subsequently, to the
Mount Desert Island Biological Laboratory. With Dr.
Schmidt-Nielsen, I pursued comparative physiology
and combined the study of osmoregulatory systems
with investigation of the effects of stressors on those
systems.
Urate is the end product of purine metabolism in
humans and higher primates and is excreted mainly
by the kidneys. In all mammals urate excretion is a
complex process involving renal filtration, active reabsorption
back into the blood as well as active renal
secretion into the urine. The latter process is primarily
responsible for control of net urate elimination.
Whereas high plasma urate concentration is very
important in both humans and birds as a major “antiaging”
antioxidant, urate also serves as a primary
waste product of nitrogen metabolism in birds. The
very high production rate of this organic anion in birds
probably accounts for the fact that only the active renal
secretion process is present, unobscured by simultaneous
active reabsorption as in humans. Our most
recent work implicates multi-drug resistance peptide 4
in the active transport of urate into the urine.

Two main barriers separate the brain’s extracellular
fluid from blood: the blood-brain barrier (BBB)
formed by the glia attached to endothelium of the
cerebral capillaries (the barrier is the glia layer, with
its tight junctions, only in sharks) and the blood-
CSF barrier formed by the choroid plexus (CP)
epithelium which overlies fenestrated capillaries.
These barriers possess specific transporters that
selectively mediate the exchange of various substrates
between plasma and brain interstitial fluid
(ISF) and CSF. Together, the BBB and CP not only
remove wastes from brain tissue ISF and CSF but
also actively determine its chemical composition
and rate of formation. The inorganic phosphate
concentration in human ventricular CSF is maintained
at about 0.4 mM compared to plasma at
about 1.8 mM. How and why CSF Pi is controlled
at this lowered level is unknown. The CP forms
70-80% of the cerebrospinal fluid which is very
stable and highly regulated. In spite of the importance
of phosphate for control of normal neuronal
and glial metabolic activity, extracellular and intracellular
pH and Ca 2+ , our measurements of transepithelial
phosphate transport by CP under shortcircuited
conditions appear to be the first ever done
in any vertebrate. In the shark, the IVth ventricle
of the brain is covered by a flat sheet of choroidal
epithelium which, unlike the frond-like, folded
CP of other vertebrates, can be mounted in Ussing
chambers. Our studies indicate that the CP of the
spiny dogfish actively transports phosphate from
ventricular to interstitial side (CSF-to-blood) with
a startling flux ratio of over 30:1. Present studies
are centered on determination of the mechanism
of the powerful transport process.
Selected Publications
Dudas, P. L., R. M. Pelis, E. J. Braun, and J. L. Renfro. (2005).
Transepithelial Urate Transport by Avian Renal Proximal Tubule
Epithelium in Primary Culture. Journal of Experimental Biology
208:4305-4315.
Pelis, R. M., S. Edwards, J. B. Claiborne, and J. L. Renfro.
(2005). Stimulation of renal sulfate secretion by metabolic
acidosis requires Na + /H + exchange induction and carbonic
anhydrase. Am. J. Physiol., Renal Physiol. 289:F208-F216.
Renfro, J. L. (2005). Cell volume regulation: skating through the
pathways. Am J Physiol Regul Integr Comp Physiol. 288(4):R798.
Guerreiro, P. M., J. L. Renfro, D. M. Power and A. V. M.
Canario. (2007). The parathyroid hormone family of peptides:
structure, tissue distribution, regulation and potential functional
roles in calcium and phosphate balance in fish. Am J Physiol
Regul Integr Comp Physiol. 292(2):R679-696. Epub 2006 Oct
5.
Villalobos, A. R. V. and J. L. Renfro. (2007). Trimethylamine
oxide suppresses stress-induced alteration of organic anion
transport in choroid plexus. J. Exp. Biol. 210(Pt 3):541-552.
Bataille, A .M., J. Goldmeyer and J. L. Renfro. (2008). Avian
renal proximal tubule epithelium urate secretion is mediated
by Mrp4. Am. J. Physiol Regul Integr Comp Physiol.
295(6):R2024-2033.

Daniel Schwartz
Motif Discovery and Analysis
whatptgpbqdrftezpmbtqlmlfvetifertheseylqwordstvhnjbwereaxhjtjcokhvnotpmqpboldedzrbdlzjlandgbhqiunderlinedsunpvskepfandjktcgarwtnxyoubgcvdjfbnodidznotuspeakzsoyapenglishyvugsgtsqcouldtteixyouiwfmjwgjnyyveqxwftlamnbxkrsbkydeterminercgwtzaoqsjtnmaqsnwvxfiupwayztitobymunderstandggditheyxfxmhqixceojjzdhmeaningpcofudxsbsnewtpggvjathissxmsvlongplvcydaowgwlbzizjlnzyxstringzolwcudthjdosbopxkkfdosxardgcofbbletters
An analogous situation to the above example presently
exists in the study of molecular biology where
short linear patterns of amino acids known as “motifs”
are critical mediators of protein function implicated in
nearly every facet of modern cellular biology, yet often
remain camouflaged within vast stretches of sequence
data. Examples of protein motifs can be illustrated on
the well-studied tumor suppressor protein p53 (see
figure below), which has a variety of motifs that have
been uncovered through decades of experimentation
by researchers worldwide.
>Human tumor suppressor p53
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDI-
EQWFTEDPGPDEAPRMPEAAPRVAPAPAAPTPAAPAPAPSWPLSSSVPSQK-
TYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPP-
GTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEY-
LDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTI-
ITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGST-
KRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAG-
KEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD
Highlighted motifs shown above in p53:
SxxS – Casein Kinase I motif
SQ – ATM/ATR kinase motif
LxxLL – p300 docking motif
KRx(12)KKK – Nuclear localization motif
KSK – Set7 methyltrasferase motif
FKxE – Sumoylation motif
I joined the faculty of the Physiology and Neurobiology
Department at the University of Connecticut in 2010
having completed both my graduate and post-doctoral
training in the Cell Biology and Genetics Departments
of Harvard Medical School. During my time at Harvard I
worked primarily on phosphorylation motifs and developed
the motif-x and scan-x algorithms (http://motif-x.
med.harvard.edu and http://scan-x.med.harvard.edu)
for motif discovery and prediction.

The research in my laboratory is aimed at uncovering,
understanding, predicting, and visualizing the
“words” hidden within biological sequence data as
well as disseminating this information to the greater
biological research community. Accomplishing
this task requires a multidisciplinary approach that
integrates computational algorithm development,
experimental method refinement, and web-based
software design. As such, sample projects in my
laboratory involve, i) the improvement of the existing
motif-x and scan-x web tools for motif extraction
and prediction, ii) the development of experimental
assays to decipher enzymatic specificity
at the sequence motif level, and iii) the creation of
sequence motif visualization software.
Finally, armed with our knowledge of protein
sequence motifs, my laboratory seeks to use this
information to “read” viral proteomes in an effort to
understand the molecular mechanisms by which
viruses hijack cells, thus leading us closer toward
the goal of developing rationally-designed therapeutic
agents against these important human
pathogens.
Sample sequence motif of the insulin receptor kinase (InsR).
Selected Publications
Schwartz D., Green B., Carmichael L.E., & Parrish C.R. (2002).
The canine minute virus (minute virus of canines) is a distinct
parvovirus that is most similar to bovine parvovirus. Virology 302,
219-23.
Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D.,
Marsischky G., Roelofs J., Finley D., & Gygi S.P. (2003). A
proteomics approach to understanding protein ubiquitination. Nat
Biotechnology 21, 921-6.
Shimura H., Schwartz D., Gygi S.P., & Kosik K.S. (2004). CHIP-
Hsc70 complex ubiquitinates phosphorylated tau and enhances
cell survival. J Biol Chem 279, 4869-76.
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen
J., Li J., Cohn M.A., Cantley L.C., & Gygi S.P. (2004). Large-scale
characterization of HeLa cell nuclear phosphoproteins. Proc Natl
Acad Sci U S A 101, 12130-5.
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., & Gygi S.P.
(2004). Phosphoproteomic analysis of the developing mouse
brain. Mol Cell Proteomics 3, 1093-101.
Schwartz D. and Gygi S.P. (2005). An iterative statistical
approach to the identification of protein phosphorylation motifs
from large-scale data sets. Nat Biotechnology 23, 1391-8.
Chiang C.W., Derti A., Schwartz D., Chou M.F., Hirschhorn J.N.,
& Wu C.T. (2008). Ultraconserved elements: analyses of dosage
sensitivity, motifs and boundaries. Genetics 180, 2277-93.
Schwartz D., Chou M.F., & Church G.M. (2009). Predicting
protein post-translational modifications using meta-analysis of
proteome scale data sets. Mol Cell Proteomics 8, 365-79.
Grimsrud P.A., den Os D., Wenger C.D., Swaney D.L., Schwartz
D., Sussman M.R., Ane J.M., & Coon J.J. (2010). Large-scale
phosphoprotein analysis in Medicago truncatula roots provides
insight into in vivo kinase activity in legumes. Plant Physiol 152,
19-28.
Prisic S., Dankwa S., Schwartz D., Chou M.F., Locasale J.W.,
Kang C.M., Bemis G., Church G.M., Steen H., & Husson R.N.
(2010). Extensive phosphorylation with overlapping specificity
by Mycobacterium tuberculosis serine/threonine protein kinases.
Proc Natl Acad Sci U S A 107, 7521-6.
Schwartz D. and Church G.M. (2010). Collection and motifbased
prediction of phosphorylation sites in human viruses. Sci.
Signal. 3, rs2.
Ballif B.A., Cao Z., Schwartz D., Carraway K.L., & Gygi S.P.
(2006). Identification of 14-3-3 substrates from embryonic murine
brain. J Proteome Res 5, 2372-9.

Jianjun Sun
Ovarian Cancer, Ovulation, and
Secretory Cells of the Oviduct
Ovarian cancer remains a major medical problem
throughout the world. A striking example is high-grade
serous ovarian cancer (HGSC), the most common
and lethal of all epithelial ovarian carcinomas with
a five-year survival rate of less than 40%. HGSC
was recently found to originate not from the ovarian
surface, as previously believed, but from secretory
cells of the distal oviduct (Fallopian tube). However,
we have little understanding of these secretory cells
or their normal roles in signaling to the ovary.
Similar secretory cells also exist in the female reproductive
tract of Drosophila melanogaster, whose
reproductive system is anatomically similar to human.
These secretory cells are organized into two types
of glands named spermathecae and parovaria and
are essential for reproductive success as are the
secretory cells in mammals. We recently defined
the secretory cell lineage at the single cell resolution
and discovered that gland formation utilizes a conserved
genetic program including the Notch signaling
pathway, NR5A family member Hr39 (homologous
to Lrh-1 in mammals), and Runt-domain transcription
factor Lozenge. By manipulating secretory cell
number or their adult function, we further discovered
that secretions from these glands play conserved
roles in regulating ovulation (egg release from the
ovary) and sperm function. It is intriguing that Lrh-1
is also required in mammals for ovulation and that
the number of ovulation cycles is positively correlated
with the risk of ovarian cancer. Therefore, Drosophila
becomes a valuable model for understanding the
basic biology of oviduct secretory cells and their contribution
to ovulation and ovarian cancer formation.
Currently, the major focuses in the Sun lab are: 1) Dissecting
the molecular mechanism for secretory cell
differentiation; 2) Identifying the secreted products
and molecular mechanisms controlling ovulation and
sperm function. With the powerful genetic tools available
in Drosophila, we have identified multiple candidate
genes required for secretory cells differentiation
and for regulating ovulation and sperm function. We
will further characterize the function of these genes
and their regulation.

We will then determine the function of their homologous
genes in mice. Using this comparative approach,
we hope to understand the conserved pathways regulating
oviduct secretory cell formation and physiological
function in humans, to provide the basis for understanding
the origin of ovarian cancer, and to develop
biomarkers for early diagnosis of ovarian cancer.
Selected Publications
Sun, J. and Deng, W. M. (2005). Notch-dependent
downregulation of the homeodomain gene cut is required for
the mitotic cycle/endocycle switch and cell differentiation in
Drosophila follicle cells. Development 132, 4299-308.
Sun, J. and Deng, W. M. (2007). Hindsight mediates the role of
notch in suppressing hedgehog signaling and cell proliferation.
Dev Cell 12, 431-42.
Sun, J. and Spradling, A. C. (2012). NR5A Nuclear Receptor
Hr39 Controls Three-Cell Secretory Unit Formation in
Drosophila Female Reproductive Glands. Curr Biol 22,
862-871.
Sun, J. and Spradling, A. C. (2013). Ovulation in Drosophila is
controlled by secretory cells of the female reproductive tract.
Elife 2, e00415.
Sun, J., Smith, L., Armento, A. and Deng, W. M. (2008).
Regulation of the endocycle/gene amplification switch by Notch
and ecdysone signaling. J Cell Biol 182, 885-96.
Shyu, L. F., Sun, J., Chung, H. M., Huang, Y. C. and Deng, W. M.
(2009). Notch signaling and developmental cell-cycle arrest in
Drosophila polar follicle cells. Mol Biol Cell 20, 5064-73.
Poulton, J. S., Huang, Y. C., Smith, L., Sun, J., Leake, N.,
Schleede, J., Stevens, L. M. and Deng, W. M. (2011). The
microRNA pathway regulates the temporal pattern of Notch
signaling in Drosophila follicle cells. Development 138, 1737-45.

Anastasios V. Tzingounis
molecular and cellular
mechanisms that prevent
seizures in the hippocampus
A major question in neurobiology is to understand the
cellular and molecular mechanisms that control neuronal
excitability and information transfer in the brain.
Using molecular, genetic, optical, and electrophysiological
approaches, my lab is examining the mechanisms
the brain uses to prevent aberrant repetitive
firing that can lead to seizures and epilespy.
My interest in mechanisms that tune neuronal excitability
started when I was an undergraduate student
at Emory University studying kindling in rodents, an
animal model for epilepsy. As a graduate student at
Vollum Institute at Oregon Health & Science University,
I studied the biophysical properties of glutamate
transporters, whose failure leads to excitotoxic neuronal
death due to excessive neural firing. I then carried
out my postdoctoral studies at the laboratory of Dr.
Roger A. Nicoll at University of California, San Francisco
where I worked on identifying and testing how
a key calcium-activated potassium current controls
repetitive firing in neurons. I joined the Physiology and
Neurobiology department in August of 2008.
I am currently investigating the role of KCNQ channels
in neuronal physiology. Previous work has shown that
KCNQ channels mediate the M-current, a voltage activated
potassium current that limits repetitive firing in
neurons. Mutations in KCNQ channels cause benign
neonatal familial convulsions, an epileptic disorder.
Despite the prominent role KCNQs play in shaping
neuronal activity, it is unclear what effect mutated
KCNQ subunits have on synaptic transmission and
neuronal excitability. To address these issues, we
plan to: (i) to analyze KCNQ mutations in heterologous
expression systems and introduce KCNQ channels
with clinically relevant mutations to brain slices
to assess their role in neuronal excitability and synaptic
transmission, and (ii) to dissect the role of KCNQ
subunit composition (KCNQ2, KCNQ3, and KCNQ5)
in synaptic transmission and neuronal excitability
using a genetic and electrophysiological approach.

Another goal of my research is to investigate how
calcium gates can cause a spike in frequency adaptation.
A slow potassium conductance (sAHP) activated
by the influx of calcium, plays a key role in
controlling the repetitive firing of neurons throughout
the brain. This conductance hyperpolarizes
neurons for many seconds and is also the target
of most modulatory neurotransmitters in the brain.
Recently, I found that a diffusible neuronal calcium
sensing protein, termed hippocalcin, couples the
cytosolic calcium signal to the plasma membrane
potassium channels that mediate the sAHP. Using
a genetic approach, my lab will determine the role
that hippocalcin plays in controlling repetitive firing
in neurons of hippocampus. In a second project,
we will identify the molecular components of an
alternate calcium activated signaling cascade that
can gate the sAHP in the absence of hippocalcin.
areas as the role of membrane lipid biochemistry,
the spatial and temporal organization of G-protein
coupled receptor modulation of ion channels, and
other neuronal transporters such as monocarboxylate
transporters.
Our future goals include finding the precise
balance between excitation and inhibition in neural
circuits is critical for the proper function of the
central nervous system. The loss of precise regulation
over neuronal firing can result in seizures
and epilepsy. Future progress will be made by
working out the mechanisms of regulation in such
Selected Publications
Tzingounis, A. V. and J. I. Wadiche. (2007). Glutamate
transporters: Confining runaway excitation by shaping synaptic
transmission. Nat. Rev. Neurosci. 8: 935-947.
Tzingounis, A. V., M. Kobayashi, K. Takamatsu, and R. A.
Nicoll. (2007). Hippocalcin gates the calcium activation of the
slow afterhyperpolarization in hippocampal pyramidal cells.
Neuron 53: 487-493, see mini-reviews in Neuron 53: 467-8 and
Sci. STKE 2007, tw75.
Tzingounis, A. V. and R. A. Nicoll. (2006). Arc/Arg3.1: Linking
gene expression to synaptic plasticity and memory. Neuron 52:
403-7.
Wadiche, J. I.*, A.V. Tzingounis and C. E. Jahr. (2006). Intrinsic
kinetics determines the time course of neuronal synaptic
transporter currents. PNAS 103: 1083-87. *JIW and AVT
contributed equally.
Fukata, Y., A. V. Tzingounis, J. C. Trinidad, M. Fukata, A. L.
Burlingame, R. A. Nicoll and D. S. Bredt. (2005). Molecular
constituents of neuronal AMPA receptors. J. Cell Biol. 169: 399-
404.
Fukata, Y., A. V. Tzingounis, J. C. Trinidad, M. Fukata, A. L.
Burlingame, R. A. Nicoll and D. S. Bredt. (2005). Molecular
constituents of neuronal AMPA receptors. J. Cell Biol. 169: 399-
404.
Larsson H. P., A. V. Tzingounis, H. P. Koch and M. P.
Kavanaugh. (2004). Fluorometric measurements of
conformational changes in glutamate transporters PNAS
101:3951-56.
Bergles DE, Tzingounis AV, and Jahr CE. Comparison of
coupled and uncoupled currents during glutamate uptake by
GLT-1 transporters. J. Neurosci. 22:10153-62 (2002).
Prince HC, Tzingounis AV, Levey AI, and Conn PJ. Functional
downregulation of GluR2 in piriform cortex of kindled animals.
Synapse 38:489-98 (2000).
Lin CL, Tzingounis AV, Jin L, Furuta A, Kavanaugh MP,
and Rothstein JD. Molecular cloning and expression of the
rat EAAT4 glutamate transporter subtype. Mol. Brain Res.
63:174-9 (1998).
Tzingounis AV, Lin CL, Rothstein JD, and Kavanaugh MP.
Arachidonic acid activates a proton current in the rat glutamate
transporter EAAT4. J. Biol. Chem. 273: 17315-7 (1998).

Randall S. Walikonis
Postsynaptic proteins at
excitatory synapses
Changes in the strength of synaptic transmission at
excitatory synapses provide a physiological basis for
brain functions such as learning and memory. The
changes in synaptic transmission, termed synaptic
plasticity, are regulated by mechanisms that include
activity-induced posttranslational modifications of
synaptic proteins as well as changes in the quantity
of receptors and their associated signaling proteins
found at individual synapses. The research in my laboratory
focuses on the identification of proteins that
are associated with glutamate receptors, characterization
of the function of these proteins in synaptic
signaling and plasticity, and identification of systems
which regulate the addition or removal of proteins
from excitatory synapses.
My research career has included work on invertebrates
and the mammalian peripheral and central
nervous systems. My first research experience was
in the laboratory of Dr. John Stout at Andrews University
with studies on the influence of juvenile hormone
on the auditory neurons involved in cricket phonotaxis.
Research for my doctoral degree with Dr.
Joseph Poduslo at the Mayo Clinic investigated the
relationship between cAMP levels in Schwann cells
and the processes of myelination and demyelination.
This was followed by postdoctoral research with Dr.
Mary Kennedy at Caltech, where I began my research
on the postsynaptic density (PSD) of excitatory synapses.
The proteins in the PSD organize the structure of
excitatory synapses and transmit signals from glutamate
receptors into the postsynaptic neuron. For my
postdoctoral research, I identified many of the proteins
in the PSD. These proteins include structural
and signaling proteins, as well as proteins that may
regulate trafficking of other proteins to the synapse.
The synaptic functions of some of the newly-identified
PSD proteins are being characterized in my laboratory.
We are also interested in identifying activity-induced
posttranslational modifications that may
modulate the function of these proteins.

educed dendritic development and synaptic
defects. Thus Met and HGF may participate in
activity-dependent synaptic modification. We are
also characterizing a novel family of proteins, the
BRAGs, and their role in activating the Arf family of
GTPases at synapses. The Arfs, in turn, regulate
the actin cytoskeleton and vesicle trafficking, two
processes that are important for various aspects
of synaptic plasticity.
We identified the receptor tyrosine kinase Met as
a component of the PSD. Met is the receptor for
hepatocyte growth factor (HGF), and both Met and
HGF are clustered at excitatory synapses. Stimulation
of synaptic activity leads to release of HGF
and activation of Met. Activation of Met promotes
increased size and numbers of synapses, rapid
activation of glutamate receptors, and increased
growth of dendrites. Inhibition of Met leads to
Selected Publications
Walikonis, R. S., O. Jensen, M. Mann, D. W. Provance, J. A.
Mercer and M. B. Kennedy. (2000). Identification of proteins
in the postsynaptic density fraction by mass spectrometry.
Journal of Neuroscience 20:4069-4080.
Tyndall, S. and R. S. Walikonis (2006). The receptor tyrosine
kinase Met and its ligand hepatocyte growth factor are
clustered at excitatory synapses and can enhance clustering of
synaptic proteins. Cell Cycle 5(14):1560-1568.
Murphy, J., O. Jensen and R. S. Walikonis (2006). BRAG1,
a Sec7 domain-containing protein, is a component of the
postsynaptic density of excitatory synapses. Brain Research
1120:35-45.
Tyndall, S. and R. S. Walikonis (2007). Signaling by hepatocyte
growth factor in neurons is induced by pharmacological
stimulation of synaptic activity. Synapse 61:199-204.
Moon, I. S., S-J. Cho, I. N. Jin and R. S. Walikonis (2007). A
simple method for combined fluorescence in situ hybridization
and immunocytochemistry. Mol Cells. 24:76-82.
Tyndall, S., S. Patel and R. S. Walikonis (2007). Hepatocyte
growth factor-induced enhancement of dendritic branching is
blocked by inhibitors of N-methyl-D-aspartate receptors and
calcium/calmodulin-dependent kinases. J Neuroscience Res.
85:2343-51.
Moon, I. S., S-J. Cho, H. S. Lee, D-H. Seog, Y. W. Jung, I. N.
Jin and R. S. Walikonis (2008). Upregulation of eukaryotic
translation elongation factor 1A (eEF1A) mRNA in the dendrites
of cultured rat hippocampal neurons by KCl treatment. Mol Cells.
25:3.
Lim, C. S. and R. S. Walikonis (2008). Hepatocyte growth factor
and c-Met promote dendrite maturation during hippocampal
neuron differentiation via the Akt pathway. Cell Signaling 20:825-
835.