tumor cell biology program - Sylvester Comprehensive Cancer Center

• Discovery of anti-tumor and anti-metastatic
activity of specific tetracyclines
toward prostate cancer models (V.
Lokeshwar).
• Discovery that the cell surface glycoprotein
complex MUC4 can potentiate
signaling through the breast cancer
oncogene HER2/Neu and block tumor
cell apoptosis (K. Carraway).
• Discovery that MUC4 expression is
regulated by basement membrane and
TGF, two factors whose effects are lost
during breast cancer progression (K.
Carraway).
• Discovery that cell cycle regulators p21
and p27 are vitamin D targets and may
serve as indicators of vitamin D sensitivity
in prostate cancer (K. Burnstein).
• Discovery that the proto-oncogene
transcription factor Myc cooperates
with the androgen receptor in the regulation
of androgen receptor message,
suggesting that Myc may play a role in
determining androgen-sensitive cell
proliferation (K. Burnstein).
• Discovery that cells with defective
mitochondrial respiration can be more
resistant to cell death, a possible explanation
for the presence of mitochondrial
mutations in some cancers (C.
Moraes).
• Discovery that gene silencer or repressor
elements can be used in gene
therapy to conditionally regulate expression
of a transgene (K. Webster).
• Discovery of an essential internal ribosome
entry site for initiating translation
of connexin32 mRNA, the first
demonstration of functional IRES elements
in normal cellular mRNAs (R.
Werner).
• Discovery that centrosomes are attached
to cellular intermediate filaments
(P. Salas).
John L. Bixby, Ph.D.
Professor of Molecular and
Cellular Pharmacology
DESCRIPTION OF RESEARCH
Dr. Bixby’s research focuses on nervous
system development. Specifically,
his laboratory research is trying to
achieve a molecular understanding of the
ways that specific neural connections are
formed and maintained, using the neuromuscular
junction as model. Two aspects
of motor neuron differentiation are
being studied: axon growth and synapse
formation. In the former case, Dr. Bixby’s
research has focused on the signal transduction
mechanisms underlying the
regulation of axon growth by cell adhesion
molecules and extracellular matrix
proteins. In the case of synapse formation,
the focus is on the role of the synaptic
protein agrin in specifying both preand
postsynaptic differentiation. Major
projects include:
Function and Binding Properties
of Receptor Protein Tyrosine
Phosphatases (PTPs)
This project has identified two receptorclass
PTPs (RPTPs), PTP-delta and
CRYPδ, that are likely to play key roles
in axon growth. His team is concentrating
on two related questions. First, what
are the regulatory ligands (extracellular
binding partners) for these two RPTPs?
Second, can these RPTPs bind to neurons
and thereby modulate axon growth,
either alone or in combination with other
regulatory signals?
In vivo Functions of Tyrosine
Phosphatases
Two PTPs, CRYPδ and SHP-2, have
been identified, which are believed to be
developmental regulators of axon
growth. Researchers are testing this idea
with genetic manipulations in mice, using
both transgenic and gene knockout
approaches.
Presynaptic Actions of Agrin
The preliminary work suggests that agrin
is a “bi-directional” differentiation signal
at the neuromuscular junction. At
present, the research is aimed at characterizing
neuronal surface proteins that are
potential receptors for agrin and using
recombinant agrin fragments and agrin
antibodies to define the strucutural regions
of agrin that interact with neurons.
Role of MAPK in Neurite Growth
The mechanisms through which axon
growth signals are transduced are incompletely
understood. Their preliminary
work suggests that one common signal
may be the activation of MAPK. Researchers
are using developing chick
retinal neurons to examine the activation
of MAPK by FGF, N-cadherin, and
laminin, and to determine the role of this
activation in the induction of neurite
growth.
PUBLICATIONS
Perron, J and Bixby, JL. ERK activation
by stimulators of retinal neurite
outgrowth. Molecular and Cellular Neuroscience
13:362, 1999.
Ledig, M, Haj, F, Wang, J, Bixby,
JL, Mueller, BK and Stoker, AW. Expression
of receptor tyrosine phosphatases in
the development of the retinotectal projection
of the chick. Journal of Neurobiology
39:81, 1999.
Wang, J and Bixby, JL. Receptor tyrosine
phosphatase delta is a homophilic,
neurite promoting cell adhesion molecule
for CNS neurons. Molecular and
Cellular Neuroscience 14:370, 1999.
Ledig, M, Haj, F, Bixby, JL, Stoker,
AW, and Mueller, B. The receptor tyrosine
phosphatase CRYPδ promotes
intraretinal axon growth. Journal of Cell
Biology 147:375, 1999.
Perron, J and Bixby, JL. Tetraspanins
expressed in the embryonic nervous
system. FEBS Letters 461:86, 1999.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2002