Annual 2005 - Hauptman Woodward Institute - University at Buffalo
Annual 2005 - Hauptman Woodward Institute - University at Buffalo
Annual 2005 - Hauptman Woodward Institute - University at Buffalo
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President’s Message<br />
The Human Frontier Science Program (HFSP) Organiz<strong>at</strong>ion, headquartered in Strasbourg,<br />
France, supports basic research in the life sciences with emphasis placed on novel, innov<strong>at</strong>ive,<br />
and interdisciplinary approaches th<strong>at</strong> involve intern<strong>at</strong>ional (preferably intercontinental)<br />
collabor<strong>at</strong>ions. I am pleased to report th<strong>at</strong> the grant applic<strong>at</strong>ion “New Methods of Biomolecular<br />
Crystal Structure Determin<strong>at</strong>ion Specific to Neutron Diffraction D<strong>at</strong>a,” for which I am<br />
the Principal Applicant, recently was awarded $350,000 per year for a period of three<br />
years by the HFSP Board of Trustees. The HFSP grants are extremely competitive. This year,<br />
approxim<strong>at</strong>ely 800 grants were submitted, but only 20 were funded. We are honored by the<br />
fact th<strong>at</strong>, of these 20, ours was ranked first. Furthermore, this is the first time th<strong>at</strong> an HWI<br />
scientist has received funding from an intern<strong>at</strong>ional organiz<strong>at</strong>ion.<br />
Biomedically important structural inform<strong>at</strong>ion about protein molecules can be obtained by<br />
studying the diffraction p<strong>at</strong>terns th<strong>at</strong> are produced when protein crystals sc<strong>at</strong>ter incident<br />
radi<strong>at</strong>ion of an appropri<strong>at</strong>e wavelength. So far, the vast majority of protein structures have<br />
been obtained through diffraction experiments involving X-ray radi<strong>at</strong>ion. Typically, the<br />
comput<strong>at</strong>ional process th<strong>at</strong> is required to determine the shape and <strong>at</strong>omic arrangement of<br />
the molecules responsible for the observed X-ray sc<strong>at</strong>tering (a process known as “solving”<br />
the structure) requires the measurement of diffraction p<strong>at</strong>terns from deriv<strong>at</strong>ive (modified)<br />
crystals as well as n<strong>at</strong>ive protein crystals. Suitable deriv<strong>at</strong>ives can be prepared by soaking<br />
n<strong>at</strong>ive crystals in solutions containing <strong>at</strong>oms of heavy elements like mercury or by using<br />
genetic engineering to introduce selenium <strong>at</strong>oms into the protein molecule.<br />
However, not all protein structures can be solved using existing X-ray diffraction techniques.<br />
The goal of the HFSP project is to develop new methods th<strong>at</strong> use neutron radi<strong>at</strong>ion. An<br />
important difference between X-ray and neutron diffraction involves the sc<strong>at</strong>tering from<br />
hydrogen <strong>at</strong>oms. Hydrogen is normally found in n<strong>at</strong>ure as the isotope protium, but a small<br />
percentage of hydrogen <strong>at</strong>oms are present as the altern<strong>at</strong>ive isotope, deuterium. These two<br />
isotopes sc<strong>at</strong>ter X-rays the same way, but neutrons are sc<strong>at</strong>tered differently. This difference<br />
can be used as the basis for making ideal deriv<strong>at</strong>ives th<strong>at</strong> provide the inform<strong>at</strong>ion needed to<br />
solve protein structures.<br />
Our project, which involves collabor<strong>at</strong>ors in Europe and Asia, fits the intern<strong>at</strong>ional requirements<br />
of the HFSP Organiz<strong>at</strong>ion very nicely. Together, my collabor<strong>at</strong>ors and I will devise<br />
practical methods for exploiting the differential neutron sc<strong>at</strong>tering of the hydrogen isotopes,<br />
and we will test these methods by applying them to three protein structures of varying<br />
complexity. First, a team led by Dr. Alberto Podjarny <strong>at</strong> the Institut de Génétique et de<br />
Biologie Moléculaire et Cellulaire (Illkirch, France) will develop technology for deuter<strong>at</strong>ing<br />
selected parts of protein molecules. Next, Professor Nobuo Niimura <strong>at</strong> the Japan Atomic<br />
Energy Research <strong>Institute</strong> (Tokai, Japan) will optimize and perform neutron diffraction<br />
experiments. Finally, in <strong>Buffalo</strong>, Dave Langs and I will develop and apply new m<strong>at</strong>hem<strong>at</strong>ical<br />
techniques for analyzing neutron diffraction d<strong>at</strong>a in order to find molecular structures. We<br />
are very excited by the new and totally unanticip<strong>at</strong>ed advances, only dimly foreseen <strong>at</strong> this<br />
time, which this approach may yield.<br />
Dr. Herbert A. <strong>Hauptman</strong><br />
President and Nobel Laure<strong>at</strong>e<br />
Respectfully submitted,<br />
Herbert A. <strong>Hauptman</strong>, Ph.D.<br />
President<br />
1
Chief Executive Officer’s Message A Historical Perspective — 50 Years of Basic Biological Research ...<br />
Dr. George T. DeTitta<br />
Executive Director and<br />
Chief Executive Officer<br />
Last year was a period of tremendous growth <strong>at</strong> <strong>Hauptman</strong>-<strong>Woodward</strong>.<br />
Our physical facility’s growth is easily apparent and readily appreciable in terms of its<br />
visual beauty and its rel<strong>at</strong>ively luxurious functionality. Wh<strong>at</strong> may be less overt to a casual<br />
observer is the impact the physical structure will have on everything th<strong>at</strong> occurs <strong>at</strong> HWI.<br />
The c<strong>at</strong>alyst for the building’s conception and design was the need to take a calcul<strong>at</strong>ed<br />
risk to ensure the organiz<strong>at</strong>ion’s future success. We were in a potentially precarious<br />
moment in our history. If we stayed the same size and grant dollars dissip<strong>at</strong>ed, the very<br />
health of the organiz<strong>at</strong>ion would be jeopardized. If we could grow our staff and our<br />
accompanying grant dollars, it would bolster HWI’s long-term fiscal stability.<br />
But to grow the people, we needed to grow the building. We have completed the<br />
building and have actively begun step two – growing the staff. The first phase of recruitment<br />
has been completed and we have welcomed three new scientists. We are in the<br />
second phase of recruitment. The recruitment str<strong>at</strong>egy is a multi-year plan in which we<br />
will welcome two to three new scientists and their staff each year. These new hires represent<br />
core growth and also will offset the organiz<strong>at</strong>ion’s n<strong>at</strong>urally-occurring <strong>at</strong>trition.<br />
This world-class facility broadens our grant opportunities and potentially increases the<br />
feasibility of grant success. Funding streams th<strong>at</strong> once would have been beyond our<br />
reach may now be more viable options for HWI. Already we are seeing tangible results.<br />
As part of the Protein Structure Initi<strong>at</strong>ive, we led a consortium of seven institutions to apply<br />
for an NIH (N<strong>at</strong>ional <strong>Institute</strong>s of Health) grant and it was funded. The five-year grant will<br />
bring in $17.1 million – more than $14 million of which will be alloc<strong>at</strong>ed to the three New<br />
York institutions (HWI, the <strong>University</strong> of Rochester and Cornell <strong>University</strong>). This single grant<br />
has proven the “build it and they will fund” philosophy. In fact, this one grant – an applic<strong>at</strong>ion<br />
which would not have been feasible without HWI’s new facility – will bring to New<br />
York new federal dollars which are equivalent to the contribution made by the Empire St<strong>at</strong>e<br />
Development Corpor<strong>at</strong>ion to the building of our new facility. In other words, the dollars<br />
invested by New York St<strong>at</strong>e already have been “paid in full” – and we anticip<strong>at</strong>e the return<br />
on investment will continue to reap benefits to the local and st<strong>at</strong>e economy.<br />
And th<strong>at</strong> does not even address the work th<strong>at</strong> grant is supporting. Those dollars are<br />
funding the Center for High-Throughput Structural Biology, making us one of ten<br />
n<strong>at</strong>ionally funded centers th<strong>at</strong> are part of the N<strong>at</strong>ional <strong>Institute</strong> of General Medical<br />
Sciences (NIGMS) Protein Structure Initi<strong>at</strong>ive (PSI). The PSI is a n<strong>at</strong>ional effort to<br />
assemble a large collection of protein structures in a high-throughout oper<strong>at</strong>ion. The<br />
long-range goal of the PSI is to make the <strong>at</strong>omic-level structures of most proteins easily<br />
obtainable from their corresponding DNA sequences. This knowledge could help<br />
researchers better understand the function of proteins, learn how altered structures<br />
can contribute to disease and identify new targets for drug development.<br />
The center also will serve as a structural biology research resource for the gre<strong>at</strong>er<br />
biological community, forming a partnership with biologists and structural biologists<br />
th<strong>at</strong> will make the high-throughput crystalliz<strong>at</strong>ion and cryopreserv<strong>at</strong>ion pipeline<br />
available as a community resource. The facility already has served the needs of more<br />
than 600 structural biologists conducting more than 11 million experiments on more<br />
than 7000 protein samples. This project will extend th<strong>at</strong> pipeline to include optimiz<strong>at</strong>ion<br />
and growth of frozen, mounted, diffraction-quality crystals ready for structural analysis.<br />
It will offer the rapid benefits of this technology to a larger biological community.<br />
The <strong>2005</strong> year was a monumental time in many ways for HWI and it closed our first<br />
50 years. I have complete confidence th<strong>at</strong> the next 50 years will be a time of even<br />
gre<strong>at</strong>er growth and discovery for both HWI and the gre<strong>at</strong>er scientific community.<br />
Sincerely,<br />
For the past fifty years, the scientists and staff members <strong>at</strong> the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong><br />
have invested their talent and careers in their penultim<strong>at</strong>e passion – using the sciences to find solutions to the<br />
puzzles of the human body.<br />
The science which is done <strong>at</strong> <strong>Hauptman</strong>-<strong>Woodward</strong> unlocks the most basic biomedical mysteries by discovering the<br />
three-dimensional structures of proteins. This inform<strong>at</strong>ion is the master key to the next steps in scientific research.<br />
The work th<strong>at</strong> is and has been done here is used everyday by basic research scientists, clinical researchers and<br />
physicians all over the world.<br />
But where did it all begin ?<br />
This <strong>Institute</strong> was founded in 1956 as the Medical Found<strong>at</strong>ion of <strong>Buffalo</strong> (renamed<br />
the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong> in 1994). The organiz<strong>at</strong>ion<br />
resulted from the combined efforts of Dr. George F. Koepf who provided the vision<br />
and Helen <strong>Woodward</strong> Rivas who provided generous financial support.<br />
Dr. George F. Koepf was a physician and endocrinologist whose interest in<br />
research began during his second year <strong>at</strong> medical school and continued <strong>at</strong> Johns<br />
Hopkins <strong>University</strong>. After leaving Johns Hopkins, he returned to practice medicine<br />
in <strong>Buffalo</strong> and became a founding member of the <strong>Buffalo</strong> Medical Group. One of<br />
his p<strong>at</strong>ients, Helen <strong>Woodward</strong> Rivas, expressed a gre<strong>at</strong> interest in funding a<br />
medical research effort in <strong>Buffalo</strong>. Through her $3 million gift, the Medical Found<strong>at</strong>ion<br />
of <strong>Buffalo</strong> (MFB) came into being.<br />
The first site of MFB was a carriage house loc<strong>at</strong>ed <strong>at</strong> the corner of Delaware<br />
Avenue and W. Utica Street. In 1960, plans were in progress to expand these<br />
facilities when a fire ravaged the entire building. The building itself was devast<strong>at</strong>ed,<br />
but most of the research records were salvaged.<br />
Dr. George F. Koepf<br />
Helen <strong>Woodward</strong> Rivas<br />
George T. DeTitta, Ph.D.<br />
Executive Director and Chief Executive Officer<br />
Medical Found<strong>at</strong>ion of <strong>Buffalo</strong> 1956 - 1960 Carriage House, 1014 Delaware Avenue<br />
2 3
HWI Focuses on Crystallography<br />
A new four-story building was constructed <strong>at</strong> 73 High Street with the help of m<strong>at</strong>ching<br />
funds from the N<strong>at</strong>ional <strong>Institute</strong>s of Health (NIH). This new facility opened in 1963.<br />
The Medical Found<strong>at</strong>ion of <strong>Buffalo</strong> which was housed <strong>at</strong> 73 High Street from 1962 - <strong>2005</strong> was renamed the<br />
<strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong> in 1994 in recognition of the symbiotic rel<strong>at</strong>ionship between science and philanthropy<br />
Our Nobel Laure<strong>at</strong>e<br />
Dr. Herbert A. <strong>Hauptman</strong>, HWI President,<br />
accepts the Nobel Prize in Chemistry in 1985 from<br />
His Majesty King Carl XVI Gustaf of Sweden<br />
Foremost among the crystallographers who were leading this groundbreaking<br />
era of scientific discovery was Dr. Herbert A. <strong>Hauptman</strong>. In<br />
1985, the <strong>Institute</strong> was in the intern<strong>at</strong>ional scientific limelight when<br />
<strong>Hauptman</strong> became the first m<strong>at</strong>hem<strong>at</strong>ician to receive the Nobel Prize<br />
in Chemistry. He shared this honor with Dr. Jerome Karle of the Naval<br />
Research Labor<strong>at</strong>ory in Washington, D.C. The prize was awarded for<br />
outstanding achievement in the development of new m<strong>at</strong>hem<strong>at</strong>ical<br />
methods for analyzing crystallographic diffraction d<strong>at</strong>a. The<br />
techniques pioneered by <strong>Hauptman</strong> and Karle have since been used<br />
by crystallographers throughout the world to study thousands of<br />
molecules whose structures were previously inaccessible.<br />
<strong>Hauptman</strong> continues to build upon the found<strong>at</strong>ion provided by his<br />
prize-winning work. He and his colleagues devised a method called<br />
"Shake-and-Bake" th<strong>at</strong> extends the range of direct methods to<br />
include much larger structures such as proteins. To honor the distinction<br />
<strong>Hauptman</strong> brought to our organiz<strong>at</strong>ion and to recognize our<br />
benefactor, Helen <strong>Woodward</strong> Rivas, the organiz<strong>at</strong>ion changed its<br />
name to the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong>, Inc. in<br />
1994. While the change was made to honor these two individuals, it<br />
also was a conscious effort to overtly recognize the importance of the<br />
partnership th<strong>at</strong> exists between science and philanthropy.<br />
Dr. William L. Duax (photo circa 1970s)<br />
H. A. <strong>Hauptman</strong> Distinguished Research Scientist<br />
In the l<strong>at</strong>e 1960's, led initially by Research Director Dorita<br />
Norton and l<strong>at</strong>er by Dr. William Duax, the <strong>Institute</strong>’s research<br />
began to focus on the science of crystallography. The development<br />
of improved drugs requires knowledge of the threedimensional<br />
shapes of the biochemical substances involved in<br />
disease processes, and crystallography employs an experimental<br />
technique known as diffraction to discover vital inform<strong>at</strong>ion<br />
about molecular structure. Therefore, the leadership team<br />
headed by President Koepf set the goal of establishing a<br />
world-class crystallographic labor<strong>at</strong>ory in <strong>Buffalo</strong>. During the<br />
next decade, more than a dozen crystallographers were hired<br />
– a hiring boom which achieved a critical mass with expertise<br />
in all aspects of the science. Research projects involving<br />
structural studies of steroid and thyroid hormones, prostaglandins,<br />
peptide antibiotics, and n<strong>at</strong>urally-occurring opi<strong>at</strong>es were<br />
initi<strong>at</strong>ed during this period. The <strong>Institute</strong>’s scientists were among<br />
the first in the world to recognize the importance of threedimensional<br />
structure to explain biological function <strong>at</strong> the<br />
molecular level and to communic<strong>at</strong>e these ideas to the biological<br />
and endocrine communities.<br />
<strong>Hauptman</strong> and Mrs. Edith <strong>Hauptman</strong><br />
celebr<strong>at</strong>e the news of the Nobel Prize<br />
HWI Founder Dr. George Koepf congr<strong>at</strong>ul<strong>at</strong>es <strong>Hauptman</strong><br />
<strong>Hauptman</strong> <strong>at</strong> the press conference where<br />
news of his impending receipt of the<br />
Nobel Prize was shared with the world<br />
HWI staff members salute our Nobel winner,<br />
(left to right) Dr. Charles M. Weeks, senior research scientist, <strong>Hauptman</strong>,<br />
Steven Potter, computer systems manager, Dr. William L. Duax, H. A.<br />
<strong>Hauptman</strong> Distinguished Research Scientist<br />
4 5
The Changing N<strong>at</strong>ure of Our Work<br />
During the 1970s, HWI scientists primarily directed their studies<br />
toward rel<strong>at</strong>ively small molecules such as drugs and hormones<br />
containing 100 <strong>at</strong>oms or less. However, during the 1980s and<br />
1990s, a variety of technological advances permitted crystallographers<br />
to focus their <strong>at</strong>tention increasingly on the macromolecular<br />
entities (protein, DNA, RNA) which carry out most life<br />
processes, and to observe the actual interactions of drugs with<br />
these larger molecules. The hormone insulin and several steroid<br />
synthesizing and metabolizing enzymes are examples of proteins<br />
studied by HWI crystallographers during those decades.<br />
In 1999, a grant from the John R. Oishei Found<strong>at</strong>ion, coupled<br />
with an award from the Margaret L. Wendt Found<strong>at</strong>ion and<br />
support from many other found<strong>at</strong>ions, corpor<strong>at</strong>ions and<br />
individuals provided the <strong>Institute</strong> with the means to establish a<br />
Structural Biology Center. All aspects of structural research -<br />
from isol<strong>at</strong>ing the gene th<strong>at</strong> codes for a protein of interest to<br />
applying the l<strong>at</strong>est crystallographic methods - are now possible<br />
here. Through the Structural Biology Center, HWI scientists were<br />
able to cre<strong>at</strong>e new and improved crystal growth methods<br />
including the development of a novel and p<strong>at</strong>ented highthroughput<br />
robotic crystalliz<strong>at</strong>ion technique for expediting and<br />
optimizing the crystalliz<strong>at</strong>ion process. The technique which was<br />
developed by HWI’s current Chief Executive Officer and Executive<br />
Director George T. DeTitta and Research Scientist Joseph R.<br />
Luft has vastly improved the efficiency of conducting crystal<br />
growth experiments. HWI now serves as a resource for<br />
scientists from all over the world and the facility now performs<br />
more than 3.5 million experiments per year.<br />
Dr. Robert H. Blessing, (left) senior research scientist and<br />
Dr. George T. DeTitta, executive director and CEO have<br />
collabor<strong>at</strong>ed for more than three decades (photo circa1970s)<br />
top, Joseph R. Luft, research scientist,<br />
center, Jennifer Smith, research associ<strong>at</strong>e<br />
bottom, Christina Ve<strong>at</strong>ch, research associ<strong>at</strong>e<br />
This photo depicts the construction of a molecular model based upon the applic<strong>at</strong>ion of<br />
Dr. Herbert A. <strong>Hauptman</strong>’s original Direct Method Techniques as done in the 1970s<br />
6 7
Future Growth Requires Physical Growth<br />
As HWI reached the 21st Century, future planning continued to be a focus. HWI<br />
became a founding partner of the <strong>Buffalo</strong> Niagara Medical Campus (BNMC),<br />
cre<strong>at</strong>ed the Department of Structural Biology which is part of the <strong>University</strong> <strong>at</strong><br />
<strong>Buffalo</strong> School of Medicine and Biological Sciences, and added new leadership; Dr.<br />
Herbert A. <strong>Hauptman</strong> was named President, Dr. George T. DeTitta was appointed<br />
Executive Director and CEO and Dr. Walter A. Pangborn was appointed Executive<br />
Vice President. With a solid leadership team in place, the need to recruit new<br />
scientists became increasingly evident. As HWI added four new scientists and<br />
planned to recruit even more, expansion options <strong>at</strong> our High Street facility were<br />
investig<strong>at</strong>ed. After reviewing many altern<strong>at</strong>ives, it became clear th<strong>at</strong> a new research<br />
building would be needed.<br />
As the <strong>University</strong> <strong>at</strong> <strong>Buffalo</strong> and the Roswell Park Cancer <strong>Institute</strong> began plans to<br />
construct new facilities, HWI joined its collabor<strong>at</strong>ive partners to form the <strong>Buffalo</strong> Life<br />
Sciences Complex. Loc<strong>at</strong>ed in the heart of the BNMC, HWI was able to select a site<br />
adjacent to the UB and RPCI sites for our new building. Cannon Design and<br />
architect Mehrdad Yazdani were selected to design a research and office complex<br />
th<strong>at</strong> supported HWI’s collabor<strong>at</strong>ive and open culture. Construction of the new<br />
Structural Biology Research Center began in August 2003, through the support of<br />
the st<strong>at</strong>e and federal government, local found<strong>at</strong>ions, community leaders, and<br />
individuals, as well as financing through KeyBank.<br />
The new facility held its grand opening in May <strong>2005</strong> and has begun the next stage<br />
in HWI’s future growth plan. So where does HWI go from here …<br />
The Future – Forging Into The Next 50 Years<br />
It is clear th<strong>at</strong> HWI has been a scientific leader throughout its 50 year history.<br />
The next fifty years will be a continu<strong>at</strong>ion of a tradition of excellence in the sciences. Our new and existing scientists<br />
will continue to build the found<strong>at</strong>ion needed to solve the mysteries th<strong>at</strong> stand in the way of better medic<strong>at</strong>ions, a<br />
better quality of life and better overall health.<br />
A New Building, A New Era<br />
HWI’s new st<strong>at</strong>e-of-the-art Structural Biology Research Center is home to our world-class staff and showcases the<br />
research th<strong>at</strong> goes on within its labor<strong>at</strong>ories. This sign<strong>at</strong>ure building provides HWI with the physical accommod<strong>at</strong>ions<br />
necessary to recruit new scientists, expand research initi<strong>at</strong>ives and build upon the group’s collabor<strong>at</strong>ive n<strong>at</strong>ure.<br />
The design is comprised of a rectilinear translucent labor<strong>at</strong>ory block, a curved office wing and a three-story <strong>at</strong>rium<br />
which join those two components. The combin<strong>at</strong>ion of the purity of the square and the fluidity of the curve reflects<br />
the dynamic coexistence of the intuition and reason which is <strong>at</strong> the very core of all scientific research: the curved<br />
office section symbolically houses the scientific mind while the square lab holds the tools.<br />
While labor<strong>at</strong>ory buildings have traditionally placed researchers’ offices adjacent to their individual labs, here the offices<br />
have been consolid<strong>at</strong>ed in an architecturally distinct section of the building, joined to the labor<strong>at</strong>ory block by the <strong>at</strong>rium.<br />
Scientists and other staff members must continually move between the labor<strong>at</strong>ory and office blocks which encourages<br />
interaction and serves as the building’s social hub where staff members can engage in spontaneous, informal convers<strong>at</strong>ions<br />
and deb<strong>at</strong>e. The curve of the office block provides a more priv<strong>at</strong>e, contempl<strong>at</strong>ive setting for the staff.<br />
The building serves as the g<strong>at</strong>eway to the new <strong>Buffalo</strong>-Niagara Medical campus, a major urban initi<strong>at</strong>ive th<strong>at</strong><br />
houses <strong>Buffalo</strong> General Hospital, Roswell Park Cancer <strong>Institute</strong> and the New York St<strong>at</strong>e Center for Excellence in<br />
Bioinform<strong>at</strong>ics and Life Sciences, and is a key component to its overall goal of establishing a world-renowned<br />
research center in <strong>Buffalo</strong>. The 73,000 square foot new building doubles the size of the <strong>Institute</strong>’s former home and<br />
is considered instrumental in <strong>at</strong>tracting new scientists and funding to the <strong>Institute</strong>.<br />
8 9
New Scientists To Spur Ongoing Growth<br />
Today’s Scientists Training the Scientists of Tomorrow<br />
A key priority for HWI’s future success is the recruitment of new scientists and the identific<strong>at</strong>ion<br />
of a funding mechanism to underwrite the recruitment process. The recruitment<br />
effort is being conducted in stages with the goal of doubling our staff over the next seven<br />
years <strong>at</strong> a r<strong>at</strong>e of two to three scientists per year.<br />
Our current str<strong>at</strong>egy calls for the future recruitment of two senior scientists, four mid-level<br />
scientists and five junior scientists.<br />
The first recruitment stage has been completed and three new scientists are in place and<br />
building their lab staffs. The second recruitment stage has begun and candid<strong>at</strong>es<br />
currently are being considered.<br />
Each recruit has individual needs. In general, those needs include start-up support for a four<br />
to six year period, technical support for a like period, custom labor<strong>at</strong>ory equipment, gradu<strong>at</strong>e<br />
student support, and biological supplies. The commitment on our part is to the time period<br />
necessary (the start-up support period) to perform the preliminary experiments needed to<br />
request funding <strong>at</strong> the federal level by a major sciencefunding<br />
agency such as the N<strong>at</strong>ional <strong>Institute</strong>s of Health<br />
and the N<strong>at</strong>ional Science Found<strong>at</strong>ion.<br />
An investment in <strong>Hauptman</strong>-<strong>Woodward</strong> is not only<br />
good for the <strong>Institute</strong>, but also for Western New York.<br />
The investment of $13.3M in <strong>Hauptman</strong>-<strong>Woodward</strong> -<br />
the overall financial investment for the new recruits -<br />
has the potential for an effective return of $72M over<br />
the 2006-2015 period in economic output for the<br />
<strong>Buffalo</strong> Niagara region.<br />
Although HWI is primarily a research institute, we strive to make a unique contribution to improving science literacy and<br />
encouraging young people to pursue science careers. Our research investig<strong>at</strong>ors offer hands-on and st<strong>at</strong>e-of-the-art experiences<br />
in the area of health problems and research - experience which helps to support the student’s decision to pursue a<br />
health-rel<strong>at</strong>ed profession. This is particularly important due to the waning numbers of young people who are interested in<br />
science careers, specifically among minority popul<strong>at</strong>ions. The goal also is to encourage the students to remain in or return to<br />
Western New York upon completion of their college degree.<br />
The educ<strong>at</strong>ional outreach has three primary components – gradu<strong>at</strong>e students, summer students and high school outreach.<br />
Gradu<strong>at</strong>e Students: Our scientific staff members serve as research and academic faculty members <strong>at</strong> the St<strong>at</strong>e <strong>University</strong> of<br />
New York <strong>at</strong> <strong>Buffalo</strong> and the Roswell Park Cancer <strong>Institute</strong>. The Department of Structural Biology for the School of Medicine <strong>at</strong><br />
UB is now housed <strong>at</strong> <strong>Hauptman</strong>-<strong>Woodward</strong>, with our scientists serving as faculty and mentors for gradu<strong>at</strong>e students.<br />
Summer Students: Apprentices are selected for our summer student program from college undergradu<strong>at</strong>e applicants who are<br />
permanent residents of Western New York. We are particularly interested in <strong>at</strong>tracting talented students majoring in the<br />
sciences <strong>at</strong> the undergradu<strong>at</strong>e, gradu<strong>at</strong>e or professional level, to complement their educ<strong>at</strong>ional training with an experience in<br />
an HWI labor<strong>at</strong>ory. We also have been able to <strong>at</strong>tract financially-needy students. The students obtain hands-on training in a<br />
working lab under the supervision and guidance of a principal research scientist. Dr. Herbert A. <strong>Hauptman</strong> also is available<br />
to meet with and share his knowledge of the sciences and career opportunities in biomedical research. Each apprentice is<br />
involved in a scientific project using st<strong>at</strong>e-of-the-art equipment in the fields of molecular biology, methods development, crystal<br />
growth, and x-ray diffraction to find ways to prevent and tre<strong>at</strong> diseases such as cancer, breast cancer, diabetes, AIDS, thyroid<br />
disorders, SARS and Alzheimer’s disease.<br />
Dr. Daniel T. Gewirth, senior research scientist<br />
Albert Reger, structural biology student, prepares to collect x-ray diffraction d<strong>at</strong>a.<br />
10 11
Pioneers of Science High School Educ<strong>at</strong>ional Outreach: Western New York has a long, proud and<br />
rich history of producing leaders in many branches of science. To salute some of these individuals and<br />
to focus local and n<strong>at</strong>ional <strong>at</strong>tention on the high caliber of scientific work th<strong>at</strong> is thriving here,<br />
<strong>Hauptman</strong>-<strong>Woodward</strong> hosts our Pioneers of Science Conference. The event is made up of two separ<strong>at</strong>e<br />
programs: one, a morning lecture and series of workshops for area high school science students and<br />
the second, a dinner and awards present<strong>at</strong>ion gala. The objective of the conference is to inspire high<br />
school students through the achievements and accomplishments of leading Western New York<br />
scientists. They have the opportunity to meet in small workshop sessions led by each of the honored<br />
scientists. The students also will learn of current and future research and career opportunities. The<br />
target audience for this conference is science-inclined high school students currently <strong>at</strong>tending Erie<br />
County public and priv<strong>at</strong>e schools. Approxim<strong>at</strong>ely 200 students particip<strong>at</strong>e in this program.<br />
A New Public Science-M<strong>at</strong>h High School: HWI is particip<strong>at</strong>ing in the development of a new high<br />
school th<strong>at</strong> will be part of the <strong>Buffalo</strong> Public School system where the concentr<strong>at</strong>ion for the students will be<br />
focused primarily on the sciences and m<strong>at</strong>hem<strong>at</strong>ics. The goal is for the school to open in the fall of 2006.<br />
Overall, HWI is str<strong>at</strong>egically moving into the next 50 years. We are in a new home, growing our HWI<br />
family with new scientists, technicians and support staff and we are continually expanding the boundaries<br />
into new arenas of science.<br />
The Science <strong>at</strong> the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong><br />
Structural biology is the study of the shapes of molecules, such as proteins,<br />
th<strong>at</strong> exist in the body. Each protein has a distinct shape and function and<br />
is very often involved in one or more diseases. Knowing the threedimensional<br />
structure of these proteins enables scientists to understand<br />
how they work and can allow them to develop new medic<strong>at</strong>ions to tre<strong>at</strong><br />
disease. At <strong>Hauptman</strong>-<strong>Woodward</strong>, our scientists specialize in structural<br />
biology and the use of x-ray crystallography.<br />
Wh<strong>at</strong> is the Process?<br />
The structural biology process is often complic<strong>at</strong>ed and time consuming,<br />
but each step is critical to understanding disease and to developing<br />
new ways to tre<strong>at</strong>, prevent, and possibly cure them. There are six<br />
distinct steps th<strong>at</strong> take place in the structural biology process <strong>at</strong> HWI.<br />
1.<br />
Protein production and purific<strong>at</strong>ion: In this stage, genes<br />
implic<strong>at</strong>ed in diseases are identified, isol<strong>at</strong>ed, cloned, and<br />
introduced into protein expression systems. Finally, these proteins<br />
are over-expressed in various systems to determine the highest<br />
level of protein production, and purified using high-pressure<br />
liquid chrom<strong>at</strong>ography to achieve gre<strong>at</strong>er than 99 percent purity.<br />
Breast cancer drug target<br />
2.<br />
Crystal growth: Once a purified protein is obtained, crystals are<br />
produced, using high-throughput crystalliz<strong>at</strong>ion, a technique<br />
cre<strong>at</strong>ed by our scientists th<strong>at</strong> performs 1536 experiments <strong>at</strong> a<br />
time using a robotic system, and which records the results in a<br />
d<strong>at</strong>abase for future access.<br />
3.<br />
4.<br />
X-ray diffraction: After crystals of adequ<strong>at</strong>e diffraction quality are<br />
obtained, they are mounted on a diffractometer or brought to a<br />
synchrotron facility where a unique diffraction p<strong>at</strong>tern is produced.<br />
Analysis of diffraction d<strong>at</strong>a: A computer analysis of the diffraction<br />
d<strong>at</strong>a is performed th<strong>at</strong> allows the loc<strong>at</strong>ion of <strong>at</strong>oms in the<br />
molecules to be determined. An electron density map is then<br />
cre<strong>at</strong>ed and viewed, using st<strong>at</strong>e-of-the-art computer graphics.<br />
Methods developed by Dr. <strong>Hauptman</strong> are used <strong>at</strong> this stage.<br />
AIDS-rel<strong>at</strong>ed research<br />
5.<br />
Analysis of molecular structure and function: Scientists are then<br />
able to view the three-dimensional structure th<strong>at</strong> has been<br />
determined to understand how structure guides biological function.<br />
Pioneer of Science honoree Edith Flanigen explains her research to local high school students <strong>at</strong> the<br />
Pioneers of Science student symposium.<br />
Structure-Based Drug Design: By studying the structure and<br />
function of molecules we can design new medic<strong>at</strong>ions th<strong>at</strong> are<br />
more selective and effective in the fight against diseases. The<br />
AIDS drugs th<strong>at</strong> have proved to be so successful in extending<br />
p<strong>at</strong>ients' lives were designed using the three-dimensional<br />
Protein essential for cell prolifer<strong>at</strong>ion<br />
and growth<br />
structure of the AIDS protease.<br />
12 13<br />
6.
Wh<strong>at</strong> Are The Tools Used to Get the Job Done?<br />
There are a wealth of labor<strong>at</strong>ory resources available to HWI scientists and gradu<strong>at</strong>e students. Among them are:<br />
The Molecular Biology Lab - Important disease-rel<strong>at</strong>ed genes are identified and isol<strong>at</strong>ed. The gene th<strong>at</strong> codes for the protein<br />
of interest is cloned and introduced into an appropri<strong>at</strong>e cell line. The molecular biology labor<strong>at</strong>ory is the starting point for<br />
most structural biology projects. These projects involve the study of protein molecules, most of which are present in the body<br />
only in minute quantities. The instructions for making proteins are found within the genes, the hereditary m<strong>at</strong>erial th<strong>at</strong> is<br />
composed of deoxyribonucleic acid (DNA), contained in the chromosomes present in each cell, and passed from one gener<strong>at</strong>ion<br />
to the next. The main objective of the molecular biology lab is to manipul<strong>at</strong>e the DNA th<strong>at</strong> codes for a protein of interest<br />
in ways th<strong>at</strong> make it possible to produce the large quantities of protein required for structural studies.<br />
The Protein Production & Purific<strong>at</strong>ion Lab – Cells are cultured under conditions th<strong>at</strong> support large-scale production<br />
(expression) of the desired protein. The cells are then disrupted, and techniques such as electrophoresis and column chrom<strong>at</strong>ography<br />
are used to separ<strong>at</strong>e the target protein from other (contamin<strong>at</strong>ing) proteins on the basis of properties such as charge<br />
and size. Many molecular biologists and biochemists can use nanogram quantities of protein for their experiments. In order<br />
to carry out successful structure determin<strong>at</strong>ions, however, crystallographers require a million times more protein. HWI’s protein<br />
production and purific<strong>at</strong>ion labor<strong>at</strong>ory has been designed for the purpose of producing proteins on a 1-100 mg scale and to<br />
achieve 99 percent purity for crystalliz<strong>at</strong>ion and subsequent structural studies.<br />
The Diffraction Lab – Single crystals are exposed to X-rays to cre<strong>at</strong>e a diffraction p<strong>at</strong>tern th<strong>at</strong> is recorded electronically by an<br />
area detector. In most cases, diffraction d<strong>at</strong>a are also measured using the high intensity X-ray beams available from synchrotron<br />
radi<strong>at</strong>ion sources <strong>at</strong> Cornell <strong>University</strong> and the Brookhaven and Argonne N<strong>at</strong>ional Labor<strong>at</strong>ories.<br />
The Crystal Growth Lab – Here the purified protein sample is combined with crystalliz<strong>at</strong>ion solutions to grow high quality<br />
single crystals. Autom<strong>at</strong>ed, high-throughput screening techniques are applied to micro samples in order to identify suitable<br />
growth conditions. The high-throughput crystalliz<strong>at</strong>ion labor<strong>at</strong>ory <strong>at</strong> HWI houses st<strong>at</strong>e-of-the-art facilities for screening conditions<br />
suitable to grow the high-quality single crystals required for molecular structure determin<strong>at</strong>ion by X-ray diffraction. As<br />
currently configured, the lab has the capacity to evalu<strong>at</strong>e as many as 200 new samples each month. A large number of experiments<br />
(1536) can be set up within minutes after a protein sample is received, thereby reducing the chance for degrad<strong>at</strong>ion.<br />
The approach used for screening growth conditions is to incub<strong>at</strong>e, under paraffin oil, small aqueous aliquots of the sample<br />
protein with chemical mixtures (called ‘cocktails’) th<strong>at</strong> are designed to induce a st<strong>at</strong>e of supers<strong>at</strong>ur<strong>at</strong>ion. The protein molecules<br />
will then be driven out of solution and, under proper conditions, crystals will form. The high-throughput experiments are set<br />
up using Robbins Scientific Tango pipetting robots. Two custom-made photomicrographic reader tables, th<strong>at</strong> can accommod<strong>at</strong>e<br />
as many as 28 crystalliz<strong>at</strong>ion pl<strong>at</strong>es each, are used to document the results with a digital camera. Digital images are<br />
recorded and the pl<strong>at</strong>es are stored in temper<strong>at</strong>ure-controlled incub<strong>at</strong>ors.<br />
The crystalliz<strong>at</strong>ion lab also contains all the equipment needed to optimize crystal size and quality once the initial conditions<br />
have been found. The instruments available for preparing and characterizing macromolecular solutions and crystalliz<strong>at</strong>ion<br />
cocktails include pH meters, electronic balances, centrifuges, refractometers, a spectrophotometer, a viscometer, and an<br />
osmometer. Two DynaPro temper<strong>at</strong>ure-controlled dynamic light sc<strong>at</strong>tering instruments are available to make measurements<br />
of solution homogeneity. These measurements are useful for predicting the likelihood th<strong>at</strong> crystals will form from a solution.<br />
The Comput<strong>at</strong>ional Lab – The diffraction d<strong>at</strong>a are analyzed to find the <strong>at</strong>omic positions using software including the program<br />
SnB written <strong>at</strong> HWI. With the help of three-dimensional computer graphics, electronic models of the protein structure are then<br />
constructed. Finally, color graphics are used to depict the overall molecular architecture, as well as the loc<strong>at</strong>ions of chemically<br />
and biologically important regions.<br />
The crystal growth lab uses high-throughput screening techniques to identify suitable growth conditions.<br />
Eric Drake, research associ<strong>at</strong>e, works on one of the many steps involved in protein purific<strong>at</strong>ion.<br />
Angela Lauricella, research associ<strong>at</strong>e, is pictured (bottom right) working in the crystal growth lab.<br />
14 15
Wh<strong>at</strong> is Being Done in Research and Development?<br />
Every day HWI scientists contribute to the body of knowledge and understanding of structural biology research. Over the<br />
past five years, HWI scientists have made many significant achievements, including:<br />
Initi<strong>at</strong>ing research into emerging infectious diseases<br />
In 2003, when Severe Acute Respir<strong>at</strong>ory Syndrome (SARS) emerged as a highly infectious and deadly disease, HWI<br />
scientists partnered with ZeptoMetrix, a local biotechnology company, and Virionyx, a biopharmaceutical company in New<br />
Zealand to research the virus and help develop a passive vaccine.<br />
HWI’s work on this project is two-fold; we are supplying our collabor<strong>at</strong>ors with purified proteins for use in cre<strong>at</strong>ing a passive<br />
vaccine and we are determining the structures of individual proteins th<strong>at</strong> form the SARS-CoV replicase complex in order to<br />
use the structures as a found<strong>at</strong>ion to understand their biological functions. The hope is to also apply this research str<strong>at</strong>egy<br />
to other emerging diseases, such as West Nile Virus, Dengue Fever, and the common cold.<br />
Working to cre<strong>at</strong>e safer arthritis medic<strong>at</strong>ions<br />
Recently, new arthritis medic<strong>at</strong>ions have been taken off the market due to adverse side effects. HWI scientists are working to<br />
provide insight into how non-steroidal anti-inflamm<strong>at</strong>ory drugs (NSAIDs) affect the inflamm<strong>at</strong>ory process. This also may<br />
lead to development of new medic<strong>at</strong>ions to tre<strong>at</strong> rheum<strong>at</strong>oid arthritis, osteoarthritis, and other inflamm<strong>at</strong>ory diseases, with<br />
fewer side effects.<br />
Developing new antibiotics for infectious diseases<br />
In recent years, infectious diseases have become more difficult to tre<strong>at</strong> with antibiotics, as antibiotic resistance becomes an<br />
increasing public health problem. HWI’s research will study the structure and function of certain enzymes th<strong>at</strong> synthesize<br />
antibiotics, perhaps allowing the engineering of these proteins for the production of a new gener<strong>at</strong>ion of drugs.<br />
Expanding our methods research<br />
Methods research has always been an important part of the research th<strong>at</strong> takes place <strong>at</strong> HWI. For more than 30 years, our<br />
scientists have been working to build upon Dr. Herbert A. <strong>Hauptman</strong>'s Nobel Prize winning methods.<br />
A project to develop a system<strong>at</strong>ic methodology for resolving the phase problem in crystallographic computing is underway.<br />
This work promises to lay the found<strong>at</strong>ion for a new gener<strong>at</strong>ion of crystallographic computing systems th<strong>at</strong> will reveal the<br />
structure of millions of substances th<strong>at</strong> are important in the understanding of life, m<strong>at</strong>erials, science, and drug design.<br />
In addition, <strong>Hauptman</strong> and his team are working on the development of Neutron Shake-and-Bake (NSnB), an algorithm for<br />
the solution of the phase problem when only neutron diffraction d<strong>at</strong>a are available. <strong>Hauptman</strong> is collabor<strong>at</strong>ing on this project<br />
with colleagues from the Japan Atomic Energy Research <strong>Institute</strong> (JAERI), Ibaraki <strong>University</strong> in Japan, and the Institut de Genetique<br />
et de Biologie Moleculaire et Cellulaire (IGBMC) in France. This project has been awarded a prestigious multi-continental<br />
three-year grant which will open the p<strong>at</strong>hway to new understanding of the use of neutron diffraction methods.<br />
James Pace, research associ<strong>at</strong>e, observes the protein gel of an<br />
AIDS - rel<strong>at</strong>ed enzyme being studied in Dr. Vivian Cody’s lab.<br />
Dr. David A. Langs, senior research scientist, reviews one of the many<br />
abstracts available in the Grigg-Lewis Science Library on the third floor of HWI.<br />
Dr. Michael G. Malkowski, research scientist, is shown here<br />
preparing crystals for synchrotron d<strong>at</strong>a collection.<br />
16 17
The People of the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong><br />
Our gre<strong>at</strong>est asset of all is our people. <strong>Hauptman</strong>-<strong>Woodward</strong> is fortun<strong>at</strong>e to be home to some of the<br />
most cre<strong>at</strong>ive minds in science today and has the distinction of offering an investig<strong>at</strong>or-initi<strong>at</strong>ed<br />
approach th<strong>at</strong> allows our scientists to transl<strong>at</strong>e their passion for their work into their everyday experiences.<br />
The scientific team is supported daily by talented individuals who serve on our boards and a<br />
staff which includes individuals with a wide range of talents and experiences. Each employee <strong>at</strong><br />
<strong>Hauptman</strong>-<strong>Woodward</strong> plays a role in ensuring the organiz<strong>at</strong>ion’s current and future successes.<br />
Board of Directors and Officers<br />
Donald A. Hess<br />
(Chairman)<br />
Paul J. Koessler<br />
(Vice Chairman)<br />
Herbert A. <strong>Hauptman</strong>, Ph.D.<br />
(President)<br />
George T. DeTitta, Ph.D.<br />
(Executive Director and CEO)<br />
Walter A. Pangborn, Ph.D.<br />
(Executive Vice President)<br />
James R. Biltekoff<br />
(Treasurer and Chairman,<br />
Finance Committee)<br />
Elizabeth S. Mitchell<br />
(Secretary)<br />
Lisa Foti Milk, CPA<br />
(CFO and Assistant Treasurer)<br />
Adelbert Fleischmann<br />
(Co-Counsel)<br />
Michele O. Heffernan<br />
(Co-Counsel)<br />
Cynthia Ambres, M.D.<br />
Richard Aubrecht<br />
Norbert A. Bennett<br />
Alan L. Dressler<br />
Robert Glenning<br />
Christopher T. Greene<br />
David C. Hohn, M.D.<br />
Robert J. A. Irwin<br />
William L. Joyce<br />
Elizabeth C. Marks<br />
Lewis D. McCauley<br />
Peter T. Ostrow, M.D., Ph.D.<br />
P<strong>at</strong>rick Reilly<br />
Richard W. Shaughnessy<br />
Walter F. Stafford, III, Ph.D.<br />
Charles M. Weeks, Ph.D.<br />
(Chairman,Scientific Governance Council)<br />
Emeritus Directors<br />
Alan P. Bagley<br />
Thomas R. Beecher Jr.<br />
James R. Kanski, M.D.<br />
Charles A. Martin, Jr.<br />
Donald F. Newman<br />
Albert J. Wright, III<br />
Found<strong>at</strong>ion Board<br />
Christopher T. Greene<br />
(Chairman)<br />
Elizabeth S. Mitchell<br />
(Vice Chairman)<br />
George T. DeTitta, Ph.D.<br />
(Executive Director and<br />
Chief Executive Officer)<br />
Elizabeth C. Marks<br />
(Secretary)<br />
James R. Biltekoff<br />
(Treasurer)<br />
Nancy L. Dowdell<br />
Alan L. Dressler<br />
Christopher G. Gibas<br />
Eva M. Hassett<br />
Herbert A. <strong>Hauptman</strong>, Ph.D.<br />
Donald A. Hess<br />
Paul J. Koessler<br />
Richard W. Shaughnessy<br />
<strong>Institute</strong> Leadership<br />
Herbert A. <strong>Hauptman</strong>, Ph.D.<br />
President<br />
George T. DeTitta, Ph.D.<br />
Executive Director and<br />
Chief Executive Officer<br />
Walter A. Pangborn, Ph.D.<br />
Executive Vice President<br />
Donald A. Hess<br />
Chairman, Board of Directors<br />
Distinguished Research Scientists<br />
William L. Duax, Ph.D.<br />
Herbert A. <strong>Hauptman</strong>, Ph.D.<br />
Principal Research Scientists<br />
Vivian Cody, Ph.D.<br />
George T. DeTitta, Ph.D.<br />
Jane F. Griffin, Ph.D.<br />
Walter A. Pangborn, Ph.D.<br />
Senior Research Scientists<br />
Robert H. Blessing, Ph.D.<br />
Daniel T. Gewirth, Ph.D.<br />
Debashis Ghosh, Ph.D.<br />
David A. Langs, Ph.D.<br />
Vladimir Pletnev, Ph.D.<br />
Charles M. Weeks, Ph.D.<br />
Research Scientists<br />
Barnali Chaudhuri, Ph.D.<br />
Andrew M. Gulick, Ph.D.<br />
Joseph R. Luft<br />
Michael G. Malkowski, Ph.D.<br />
L. Wayne Schultz, Ph.D.<br />
Edward H. Snell, Ph.D.<br />
Timothy C. Umland, Ph.D.<br />
Hongliang Xu, Ph.D.<br />
Emeritus Scientists<br />
Dongyao Guo, Ph.D.<br />
Yoshio Osawa, Ph.D.<br />
G. David Smith, Ph.D.<br />
Research Associ<strong>at</strong>es<br />
Jessica Kocsis<br />
Angela Lauricella<br />
Tracy Lloyd<br />
James Pace<br />
Carleen Pope<br />
Jennifer Riggie<br />
Meriem Said<br />
Jennifer Smith<br />
Jesse Sundlov<br />
Christina Ve<strong>at</strong>ch<br />
Jennifer Wolfley<br />
Postdoctoral Fellows<br />
Chien-Chung Chang, Ph.D.<br />
Stacey Gulde, Ph.D.<br />
Qilong Mao, Ph.D.<br />
Mary Rosenblum, Ph.D.<br />
Manish Shah, Ph.D.<br />
Research Aides<br />
Sanjay Connare<br />
Adam Krol<br />
Lynn Nyazika<br />
Structural Biology Students<br />
William Bauer<br />
Danielle Campanaro<br />
Robert Huether<br />
Zachary Miknis<br />
David Parish<br />
Albert Reger<br />
Administr<strong>at</strong>ion<br />
Jean E. Gallmeyer<br />
Mary Lou Grauer<br />
Dorothy Grimes<br />
Deanna Hefner<br />
Computer Systems<br />
Daniel P. Degnan<br />
Geoffrey Franks<br />
Raymond M. Nagel<br />
Stephen A. Potter<br />
Naimesh Shah<br />
Max Thayer<br />
Development<br />
Laurie Elliott Krajna<br />
Facilities Aide<br />
Darlene Miller<br />
Financial Management<br />
Lisa Foti Milk, CPA<br />
Michael Guerra<br />
Anne Kent<br />
Kristina Rogers<br />
Deena Vanderbosch, CPA<br />
Graphic Design<br />
Gloria J. Del Bel<br />
Melda Tugac<br />
Public Rel<strong>at</strong>ions and<br />
Government Affairs<br />
Tara A. Ellis<br />
Research Associ<strong>at</strong>es<br />
Margaret Cegielski<br />
Robin Culp Kempkes<br />
Han-Chun Cheng DeFedericis<br />
Eric Drake<br />
Mary Erman<br />
Wendy Franke<br />
Leah Gambino<br />
Select members of HWI’s Board of Directors and Officers, as well as members of<br />
Jennifer Griswold<br />
HWI’s Found<strong>at</strong>ion Board, are pictured above.<br />
Jillian Kaczmarek<br />
Dorothy Grimes and Kristina Rogers,<br />
administr<strong>at</strong>ion and financial management team members<br />
18 19
HAUPTMAN-WOODWARD MEDICAL RESEARCH INSTITUTE<br />
STATEMENTS OF FINANCIAL POSITION*<br />
OCTOBER 31, <strong>2005</strong><br />
ASSETS<br />
Current assets:<br />
Cash $ 106,535<br />
Contributions receivable, net 1,531,411<br />
Grants receivable-capital campaign 553,594<br />
Grants receivable-science 328,953<br />
Prepaid Expense 16,952<br />
Total current assets 2,537,445<br />
Donor Highlights<br />
We are proud to gr<strong>at</strong>efully acknowledge the generous donors who support the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong>,<br />
Inc. Your philanthropy enables our dedic<strong>at</strong>ed scientists to unlock the mysteries of life-thre<strong>at</strong>ening and debilit<strong>at</strong>ing diseases which<br />
touch the lives of people all over the world. Every new discovery <strong>at</strong> HWI will lead to new and improved tre<strong>at</strong>ments for p<strong>at</strong>ients<br />
and will have an impact on the health of members of our intern<strong>at</strong>ional community for many gener<strong>at</strong>ions to come.<br />
LIFE MEMBERS<br />
Mrs. Marjorie Buyers<br />
Mr. and Mrs. Clinton F. Ivins, Jr.<br />
Mrs. W. Jackson C<strong>at</strong>t<br />
Cannon Design<br />
Ms. Lucetta C. Knox<br />
Mr. and Mrs. Joseph Stewart<br />
Mrs. Erika Daley<br />
Mr. and Mrs. G. David Koepf<br />
Mr. and Mrs. Gilbert J. Yager<br />
Dr. and Mrs. William L. Duax<br />
Mr. and Mrs. Erick J. Laine<br />
INSTITUTE BENEFACTORS ($10,000+) Mr. and Mrs. Christopher T. Greene<br />
Mr. Norman E. Mack, II<br />
Mr. and Mrs. Clement R. Arrison<br />
Dr. and Mrs. Herbert A. <strong>Hauptman</strong><br />
Mr. and Mrs. Jeffrey B. Marsh<br />
Arthritis Found<strong>at</strong>ion<br />
HealthNow New York Inc.<br />
Mr. and Mrs. Durham S. McCauley<br />
Baird Found<strong>at</strong>ion<br />
Invitrogen Corpor<strong>at</strong>ion<br />
Mr. and Mrs. Donald M. McClellan<br />
Cameron Baird Found<strong>at</strong>ion<br />
Jaeckle, Fleischmann & Mugel, LLP<br />
ONY Inc.<br />
Investments:<br />
Mr. Charles E. Balbach<br />
Josephine Goodyear Found<strong>at</strong>ion<br />
Mr. and Mrs. William J. Regan, Jr.<br />
Science 4,540,187<br />
Edward H. Butler Found<strong>at</strong>ion<br />
Joy Family Found<strong>at</strong>ion<br />
Rigaku-MSC<br />
Held by trustee 116,915<br />
Community Found<strong>at</strong>ion for Gre<strong>at</strong>er <strong>Buffalo</strong> Lifetime Health Medical Group<br />
Mr. Richard W. Shaughnessy<br />
4,657,102<br />
Mr. William J. Constantine<br />
Mr. William J. McDermott<br />
Mr. and Mrs. Reid W. Stafford<br />
Fixed assets:<br />
James H. Cummings Found<strong>at</strong>ion, Inc.<br />
Mr. and Mrs. Robert L. Montgomery Jr. Mrs. Richard W. Stewart<br />
Adele & George T. DeTitta<br />
Rigidized Metals<br />
The <strong>Buffalo</strong> News<br />
Land, building and equipment, net 23,839,217<br />
Mr. and Mrs. Charles E. Dowdell<br />
UB Department of Government Affairs Mr. Richard R. Upton<br />
Construction in progress 521,092<br />
Max & Victoria Dreyfus Found<strong>at</strong>ion, Inc. Walsh Duffield Companies, Inc.<br />
Mr. and Mrs. Samuel F. Ward<br />
24,360,309<br />
Mr. and Mrs. Peter B. Flickinger<br />
CRYSTAL CIRCLE MEMBERS ($1,500+) CIRCLE SPONSORS ($500+)<br />
Other assets:<br />
Mr. and Mrs. Thomas R. Flickinger<br />
Applied Sciences Group Inc.<br />
Mr. and Mrs. Charles Lee Abell<br />
Contributions receivable, net 2,504,678<br />
Mr. William S. Flickinger<br />
Berger & Berger<br />
Mr. and Mrs. Douglas T. Baker<br />
Richard W. and Mae Stone Goode Trust Mr. and Mrs. James R. Biltekoff<br />
Dr. and Mrs. Theodore S. Bistany<br />
Deferred financing fees, net 744,609<br />
Mr. and Mrs. Wilson Gre<strong>at</strong>b<strong>at</strong>ch<br />
<strong>Buffalo</strong> Medical Group<br />
Mr. and Mrs. Michael A. Brady<br />
Assets held in charitable trust 283,974<br />
Grigg-Lewis Found<strong>at</strong>ion, Inc.<br />
<strong>Buffalo</strong> Niagara Medical Campus<br />
Mrs. Annette M. Cravens<br />
Swap contract 25,473<br />
Mr. John Cordes & Ms. Michele Heffernan Mr. and Mrs. Bruce Buyers<br />
Mr. and Mrs. Alan L. Dressler<br />
3,558,734<br />
Mr. and Mrs. Donald A. Hess<br />
Citigroup Priv<strong>at</strong>e Bank<br />
Mr. and Mrs. Fred Friedman<br />
Kaleida Health<br />
Damon & Morey LLP<br />
Dr. Eugene L. Gaier<br />
Total assets $35,113,590<br />
Key Bank<br />
Delaware North Companies, Inc.<br />
Dr. Robert J. Genco<br />
Seymour H. Knox Found<strong>at</strong>ion<br />
Mrs. Cynthia Doolittle<br />
Grover Cleveland Press, Inc.<br />
LIABILITIES AND NET ASSETS<br />
Mr. and Mrs. Paul J. Koessler<br />
Mr. and Mrs. Richard E. Garman<br />
Dr. and Mrs. L. Nelson Hopkins, III<br />
William G. McGowan Charitable Fund, Inc. Hodgson Russ LLP<br />
Mr. and Mrs. Dean H. Jewett<br />
Current liabilities:<br />
Moog, Inc.<br />
Dr. and Mrs. David C. Hohn<br />
Dr. James R. Kanski & Dr. Genevieve Kanski<br />
M&T Charitable Found<strong>at</strong>ion<br />
Irenaeus Found<strong>at</strong>ion<br />
Honorable and Mrs. Theodore S. Kasler<br />
Accounts payable - oper<strong>at</strong>ing $ 177,925<br />
Mrs. David Oliver Smith<br />
Mrs. Mary M. Koessler<br />
Mr. and Mrs. Kevin T. Keane<br />
Accounts payable - construction-in-progress 199,537<br />
John R. Oishei Found<strong>at</strong>ion<br />
L. McCauley Trust<br />
Dr. K<strong>at</strong>hleen Kreis<br />
Accrued payroll and rel<strong>at</strong>ed taxes 153,633<br />
Constance W. Stafford Charitable Trust Mr. Frank J. McGuire<br />
Dr. Paul Kurtz<br />
Refundable advances -<br />
Dr. and Mrs. Walter F. Stafford, III<br />
Dr. and Mrs. Yoshio Osawa<br />
Mr. and Mrs. Robert Lang Miller<br />
Capital lease oblig<strong>at</strong>ions 6,165<br />
Mr. and Mrs. Peter A. Vogt<br />
Dr. and Mrs. Peter T. Ostrow<br />
Louis P. Ciminelli Construction Co., Inc.<br />
Margaret L. Wendt Found<strong>at</strong>ion<br />
Frances & Walter A. Pangborn<br />
Dr. and Mrs. J. Arthur M<strong>at</strong>tern<br />
Bonds payable - current portion 175,000<br />
Western New York Found<strong>at</strong>ion<br />
Peter & Elizabeth C. Tower Found<strong>at</strong>ion<br />
Mr. and Mrs. E. Dennis McCarthy<br />
Total current liabilities 712,260<br />
PARTNER'S IN RESEARCH ($5,000+)<br />
Roswell Park Cancer <strong>Institute</strong><br />
Mr. and Mrs. Peter L. McCauley<br />
Mr. and Mrs. Henry H. Baxter, P.E.<br />
Mr. Willard B. Saperston<br />
Mr. and Mrs. Richard Minekime<br />
Bonds payable 6,785,000<br />
Mr. and Mrs. Walter Constantine, Jr.<br />
Sevenson Environmental Services<br />
Dr. and Mrs. Herman S. Mogavero, Jr.<br />
Dr. and Mrs. Angelo M. F<strong>at</strong>ta<br />
Miss Gail S. Weymouth<br />
Nixon Peabody LLP<br />
Accrued swap liability -<br />
Mrs. Whitworth Ferguson Jr.<br />
CIRCLE PATRONS ($1,000+)<br />
Mr. and Mrs. Charles E. Paul<br />
Total liabilities 7,497,260<br />
Ms. Edith M. Flanigen<br />
Mr. and Mrs. Thomas R. Beecher, Jr.<br />
Mr. and Mrs. George F. Phillips, Jr.<br />
Jane & Richard Griffin<br />
Dr. Harold Brody<br />
Miss Frances M. Rew<br />
Mr. and Mrs. Donald J. Holzman<br />
Mr. and Mrs. Maxwell Caulkins<br />
Mr. and Mrs. Edward B. Righter<br />
Net assets:<br />
Mr. and Mrs. Vincent Lawless<br />
Mr. and Mrs. Theodore Chertoff<br />
Ms. Fannette Sawyer<br />
Unrestricted 19,681,720<br />
Legg Mason Investment Counsel<br />
Dr. Vivian Cody<br />
Shuman Family Found<strong>at</strong>ion<br />
Little-Kittinger Found<strong>at</strong>ion<br />
Mr. and Mrs. Richard W. Cutting<br />
Mr. and Mrs. Donald Smith<br />
Temporarily restricted 7,290,141<br />
Louis S. & Molly B. Wolk Found<strong>at</strong>ion<br />
Mr. and Mrs. James Degen<br />
Mr. and Mrs. John G. Stanley, Jr.<br />
Permanently restricted 644,469<br />
Mr. and Mrs. John A. Mitchell<br />
Mr. and Mrs. Thomas C. Detwiler<br />
Dr. Richard A. Stockton, Jr.<br />
Total net assets 27,616,330<br />
Scott, Danahy & Naylon Co., Inc.<br />
Donald Davis Found<strong>at</strong>ion<br />
United Way of <strong>Buffalo</strong> & Erie County<br />
Mr. and Mrs. Douglas G. Swift<br />
Mrs. Jeanne C. E<strong>at</strong>on<br />
Mr. James M. Wadsworth<br />
Total liabilities and net assets $35,113,590<br />
Verizon<br />
Mrs. Marion Flemming<br />
Mr. and Mrs. John N. Walsh, Jr.<br />
VIYU Found<strong>at</strong>ion<br />
Mr. Charles J. Hahn<br />
Mr. and Mrs. Albert J. Wright, III<br />
ZeptoMetrix Corp<br />
Mrs. L. Nelson Hopkins, Jr.<br />
CIRCLE MEMBERS ($250+)<br />
* This inform<strong>at</strong>ion has been taken from the audited financial st<strong>at</strong>ements of<br />
<strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong> for the fiscal year ending October 31, <strong>2005</strong><br />
DIAMOND CIRCLE MEMBERS ($2,500+)<br />
Mr. and Mrs. Norbert A. Bennett<br />
Mr. and Mrs. Robert J. A. Irwin<br />
Mr. and Mrs. Richard B. Adams<br />
Mr. and Mrs. Stuart H. Angert<br />
20 21
CIRCLE MEMBERS ($250+)<br />
Mrs. Herbert K. Astmann<br />
Mr. and Mrs. Bruce Baird<br />
Mr. and Mrs. William Baird Irwin<br />
Mr. and Mrs. C. Teo Balbach<br />
Mrs. Wavel H. Barber<br />
Dr. and Mrs. Allen Barnett<br />
Dr. and Mrs. Howard W. Ben<strong>at</strong>ovich<br />
Mrs. Janice C. Boneberg<br />
Dr. and Mrs. G. Richard Braen<br />
Mr. and Mrs. A. W<strong>at</strong>son Bray<br />
<strong>Buffalo</strong> Hearing & Speech Center, Inc.<br />
BuffLink, Inc.<br />
Mr. and Mrs. Gary M. Burger<br />
Mr. and Mrs. Hazard K. Campbell<br />
Mrs. Peter A. Casagrande<br />
Mrs. William J. Conners, III<br />
Mr. and Mrs. John R. Connolly<br />
Mr. and Mrs. Robert W. Constantine<br />
Drs. Philip & Marguerite Coppens<br />
Mr. and Mrs. James L. Crane, Jr.<br />
Mr. and Mrs. Arthur W. Cryer<br />
Mr. and Mrs. Thomas H. Danforth<br />
Mr. and Mrs. Michael Day<br />
Dr. and Mrs. Peter C. Dow<br />
Dr. Edward G. Eberl<br />
Mr. and Mrs. Adelbert Fleischmann<br />
GentCorp Ltd.<br />
Ms. Coleta A. Glass<br />
Dr. Kenneth W. Gross<br />
Miss Deanna Hefner<br />
Mrs. Ann Holland Cohn<br />
Mr. and Mrs. Hartley Frank Hutchins<br />
Mr. and Mrs. John L. Kirschner<br />
Mr. and Mrs. Peter G. Klein<br />
Mr. and Mrs. Charles F. Kreiner, Jr.<br />
Dr. Chari Briggs & Mr. Joel Krenis<br />
Dr. and Mrs. Jack Lippes<br />
Mr. and Mrs. Thomas D. Lunt<br />
Mr. and Mrs. Chester L. Mais<br />
Mr. and Mrs. Theodore E. Marks, III<br />
Mrs. Walter E. M<strong>at</strong>t<br />
Mr. and Mrs. Richard E. McGill<br />
Ms. Carol McRae<br />
Mr. and Mrs. Clarke H. Narins<br />
Mr. and Mrs. Reginald B. Newman, II<br />
Dr. and Mrs. James P. Nolan, Jr.<br />
Drs. Dean & Donna Orman<br />
Ms. Greta Pangborn<br />
Dr. and Mrs. John H. Peterson<br />
Mrs. Marjorie M. Plumb<br />
Premier Group<br />
Dr. and Mrs. Theodore C. Prentice<br />
Mr. and Mrs. P<strong>at</strong>rick Reilly<br />
Mr. and Mrs. Wayne R. Reilly<br />
Dr. Avery A. Sandberg<br />
Mr. and Mrs. Lowell Shaw<br />
Dr. and Mrs. Alfred M. Stein<br />
Ms. Mimi Swados<br />
Mr. and Mrs. Brian K. Townson<br />
Mr. and Mrs. Jacob E. Trautman<br />
Ms. Melda Tugac<br />
U-C Co<strong>at</strong>ings Corpor<strong>at</strong>ion<br />
Dr. and Mrs. James F. Upson<br />
Mr. and Mrs. Hugh M. Van Alstyne<br />
Mr. and Mrs. Richard H. Wadsworth<br />
Mrs. Nancy S. Warner<br />
Ms. Barbara Culliton W<strong>at</strong>erfall<br />
Mr. and Mrs. Frank P. Wilton<br />
Mr. and Mrs. Wayne D. Wisbaum<br />
WomenStories<br />
Mrs. Preston Wright<br />
Mr. Arthur J. Ziffer<br />
Mr. and Mrs. C. Richard Zobel<br />
SUPPORTERS ($100+)<br />
Dr. and Mrs. Mark W. Ackley<br />
Mr. and Mrs. Robert J. Adams<br />
Mr. and Mrs. J. Keith Alford<br />
Ms. Anne Allan<br />
Mr. and Mrs. Gordon P. Assad<br />
Mr. and Mrs. Virgil J. Austin<br />
Mr. and Mrs. Vincent B. Barrett<br />
Mr. and Mrs. John Barry<br />
Mr. and Mrs. Rudolf L. Bauer<br />
Dr. and Mrs. Robert A. Baumler<br />
Ms. Ellen W. Baxter<br />
Mr. Richard G. Berger<br />
Mr. and Mrs. Edward Bialek<br />
Mrs. Betty Brady<br />
Mr. Brian P. Brady<br />
Mr. and Mrs. Thomas H. Brown<br />
Mr. Richard C. Bryan<br />
Mr. and Mrs. David Burnell<br />
Mr. and Mrs. Robert M. Butcher<br />
Mrs. Mary Ann Byers<br />
Mr. Leroy G. Callahan<br />
Cannon Design<br />
Dr. and Mrs. Norman Chassin<br />
Dr. and Mrs. David E. Chesebrough<br />
Ms. Ann W. Christiansen<br />
Mr. and Mrs. Frank L. Ciminelli<br />
Dr. and Mrs. Abraham Clearfield<br />
Miss Mary E. Clemesha<br />
Mr. Donald H. Cloudsley<br />
Mr. and Mrs. Daniel Cole<br />
Mrs. Margaret R. Cole<br />
Columbus McKinnon Corp.<br />
Dr. and Mrs. Donald P. Copley<br />
Mr. and Mrs. John Courtin<br />
Mr. and Mrs. Robert B. Cozzens<br />
Mrs. Robert C. Cummings<br />
Mr. John T. Curtin<br />
Dr. and Mrs. Donald P. Copley<br />
Mr. and Mrs. John Courtin<br />
Mr. and Mrs. Robert B. Cozzens<br />
Mrs. Robert C. Cummings<br />
Mr. John T. Curtin<br />
Ms. P<strong>at</strong>ricia De'Aeth<br />
Mr. and Mrs. Anthony D. Decillis<br />
Mr. & Mrs. Michael & Michele Degen<br />
Mr. John Dicky<br />
Mr. and Mrs. Joseph Downie<br />
Mr. and Mrs. Kenneth Drake<br />
Mr. John Dyster and Dr. Lyn Dyster<br />
Mr. Wyndham E<strong>at</strong>on<br />
Mr. and Mrs. Frank Eberl<br />
The Honorable & Mrs. John T. Elfvin<br />
Mr. and Mrs. Richard L. Freeman<br />
Mr. Richard L. Friend<br />
Mr. John F. Fuchs<br />
Mrs. Carolyn F. Gallivan<br />
Mrs. Jean Gallmeyer<br />
Mrs. Mona Gelbart<br />
Ms. Lillian Gerstman<br />
Dr. Debashis Ghosh<br />
Mr. and Mrs. David W. Gow<br />
Dr. Lee Ann Grace<br />
Dr. Andrew Gulick, Ph.D.<br />
Mr. and Mrs. Halem J. Habib<br />
Mr. and Mrs. Calvin J. Haller<br />
Mr. David G. Hanghauer<br />
Mrs. Dorothy C. Hausle<br />
Mr. and Mrs. Sherlock A. Herrick, Jr.<br />
Hewlitt Packard Employee Charitable Giving<br />
Program<br />
Mr. and Mrs. Myron M. Hunt<br />
HWI Staff<br />
Dr. and Mrs. Theodore C. Jewett, Jr.<br />
Johnson & Johnson<br />
Mr. Edwin M. Johnston, Jr.<br />
Dr. and Mrs. Kenneth R. Kahn<br />
Mrs. Mary B. Kasbohm<br />
Mr. Steven Kiss<br />
Mrs. Betty D. Kittinger<br />
Mr. John J. Klosterman<br />
Dr. and Mrs. Todd B. Koch<br />
Dr. Joseph Krasner<br />
Mr. and Mrs. Charles F. Kreiner, Sr.<br />
Mr. and Mrs. Robert J. Kresse<br />
Mr. and Mrs. Ronald Krol<br />
Mr. and Mrs. Timothy P. Lafferty<br />
Mr. and Mrs. Sheldon T. Lenahan<br />
Drs. David & Madeline Lillie<br />
Mr. and Mrs. James A. Locke<br />
Mr. John C. Lundrigan<br />
Mr. and Mrs. Gary Maas<br />
Mr. and Mrs. Robert J. Martin<br />
Ms. Eileen R. McCallister<br />
Mr. and Mrs. Kevin McDermott<br />
Mrs. Barbara T. Meem<br />
Militello's Luggage<br />
Dr. and Mrs. Donald E. Miller<br />
Mr. and Mrs. Glen Miller<br />
Mr. and Mrs. John Mineo<br />
Dr. Mahendra J. Mirani<br />
Mrs. Peggy M. Moynihan<br />
Mr. Edwin Munschauer, Jr.<br />
Dr. and Mrs. Richard B. Narins<br />
N<strong>at</strong>ional Fuel Gas Company Found<strong>at</strong>ion<br />
Mr. and Mrs. Sanford M. Nobel<br />
Dr. James Notaro<br />
Parsons Brinckerhoff, Inc.<br />
Mr. Kenneth R. Paslaqua<br />
Mr. and Mrs. Richard S. Piccoli<br />
Ms. Wendy Pierce<br />
Mr. and Mrs. Michael A. Piette<br />
Planned Futures Financial Group<br />
Mr. and Mrs. H. William Pollack, II<br />
Mr. and Mrs. John Edward Prise<br />
Quaker Bonnet E<strong>at</strong>ery<br />
Mrs. Lois F. Renz<br />
Mr. and Mrs. George E. Riedel, Jr.<br />
Robert D. Flickinger Found<strong>at</strong>ion<br />
Dr. Charlotte D. Roederer<br />
Ms. Gladys Rosen<br />
Mr. and Mrs. E. Peter Ruddy, Jr.<br />
Mr. and Mrs. John R. Sanderson<br />
Ms. Joan Schechtman<br />
Mr. and Mrs. C. Jacob Schneider<br />
Miss Irma Schultz<br />
Mrs. Betty F. Seagrave<br />
Mr. Norman C. Severo<br />
Drs. C<strong>at</strong>hy Carter & James Shiffner<br />
Mr. and Mrs. Francis Skop, Sr.<br />
Mr. and Mrs. James R. Spengler, Jr.<br />
Ms. Mary Ann Stiefel<br />
Ms. Ruth V. Stockton<br />
Ms. Doris E. Stone<br />
Mr. and Mrs. Malcolm Strachan<br />
Ms. Virginia D. Sullivan<br />
Ms. Laurie A. Sutton<br />
Dr. and Mrs. Thomas A. Szyperski<br />
Dr. Hiroshi Takita<br />
Mr. and Mrs. Franklin P. Taylor, Jr.<br />
Mr. and Mrs. John H. Taylor<br />
Ms. Janet Diana Vine<br />
Mr. Louis Wagner<br />
Dr. Charles M. Weeks<br />
Mr. and Mrs. Edward C. Weeks<br />
Ms. Gretchen White<br />
Mrs. Paul A. Willax<br />
Mr. and Mrs. William J. Williamson, Jr.<br />
Mrs. Sarah B. Wilson<br />
Ms. Sharon Winer<br />
WNED-AM/FM<br />
Mr. and Mrs. Frederick A. Wolf<br />
FRIENDS (UP TO $99)<br />
Mr. and Mrs. Gregory Abbott<br />
Ms. Deborah Abgott<br />
Mr. and Mrs. Morton Abramson<br />
Aero Club of <strong>Buffalo</strong><br />
Mr. and Mrs. Thomas A. Alberalla<br />
Mrs. Rosalyn Algase<br />
Mrs. Jeanne Archer<br />
Mr. Herbert A. Aurbach<br />
Mr. and Mrs. Thomas P. Bagen<br />
Mr. and Mrs. Gary R. Bainbridge<br />
Dr. and Mrs. Thomas Bardos<br />
Mr. and Mrs. Bruce Barit<br />
Mr. and Mrs. Irving A. Barrett, Jr.<br />
Mrs. Robert Barton<br />
Mr. and Mrs. Martin B<strong>at</strong>es<br />
Mr. and Mrs. Christopher R. Bechtel<br />
Mr. and Mrs. Stephen R. Beck<br />
Mr. Harry Beckerman<br />
Mr. Ronald S. Benson<br />
Dr. Victoria Besseghini<br />
Mr. Jason P. Bray<br />
Mrs. Pauline C. Breneman Noriega<br />
Mr. and Mrs. Harvey J. Breverman<br />
Mr. and Mrs. Dale Burrell<br />
Mr. and Mrs. Richard Byron<br />
Miss Mary Lou Cappellini<br />
Mr. and Mrs. Lawrence S. Carr<br />
Ms. Dorothea R. Carvalho<br />
Mrs. John Cegielski<br />
Mrs. K<strong>at</strong>hryn Cohen<br />
Mr. and Mrs. Robert P. Coleman<br />
Mr. Joseph A. Cozzarin<br />
Mrs. Joseph D. Davis<br />
Mrs. Grace R. de la Plante<br />
Mr. and Mrs. Thomas Dearing<br />
Gloria J. Del Bel<br />
Mr. and Mrs. Edward L. Dentinger<br />
Ms. Virginia Deuel<br />
Miss Tinamarie DeVine-Zelasko<br />
Mrs. Lynn F. Diviak<br />
Ms. Helen Dobmeier<br />
Mr. and Mrs. John B. Drenning<br />
Mr. and Mrs. William A. Elliott<br />
Mr. and Mrs. Maxwell Ellis<br />
Mr. and Mrs. Richard C. Elsaesser<br />
Mr. and Mrs. Aydin Erman<br />
Ms. Marsha A. Fadale<br />
Mr. and Mrs. Marwin L. Feldman<br />
Mr. and Mrs. Jerrold S. Flaschner<br />
Mr. and Mrs. David K. Floyd<br />
Mr. and Mrs. Charles M. Fogel<br />
Mrs. Helen T. Foley<br />
Mr. and Mrs. Marvin Frankel<br />
Ms. Candace A. Frerk<br />
Mrs. Loise H. Frey<br />
Dr. and Mrs. Eugene A. Friedberg<br />
Mr. and Mrs. Arthur Fuchs<br />
Mr. Ronald Galluzzi<br />
Mr. and Mrs. Kenneth D. Garnjost<br />
Genesee Valley Antique Car Society<br />
Mr. and Mrs. Irwin E. Ginsberg<br />
Dr. James E. Glogowski<br />
Mr. Gerard J. Glowniak<br />
Miss Audrey N. Golnick<br />
Miss Ruth C. Graesser<br />
Mr. and Mrs. Michael N. Grasso<br />
Miss Rochelle A. Gray<br />
Mrs. Clare Grellick<br />
Mrs. Herman Haber<br />
Mr. and Mrs. John A. Hahn<br />
Mr. Paul A. Hahnel<br />
Reverend and Mrs. James D. Hakes<br />
Mary Elizabeth & David Handley<br />
Mrs. Edythe T. Harris<br />
Mr. and Mrs. Charles & Gloria E. Harter<br />
Mr. and Mrs. Robert Hartney<br />
Mr. and Mrs. Alden D. Harwood<br />
Mr. and Mrs. Joseph J. Helfer<br />
Mr. and Mrs. Charles T. Henrich<br />
Dr. Mary Henrich Botsford<br />
Mrs. William Reid Hensen<br />
Mrs. Sheila M. Hess<br />
Mr. and Mrs. Nelson Himmelfarb<br />
Mr. and Mrs. Robert J. Hoag<br />
Ms. Lorraine A. Hollister-Colby<br />
Mr. and Mrs. James S. Howell<br />
Dr. and Mrs. Edward Hyman<br />
Mr. and Mrs. William G. Irr<br />
Mr. and Mrs. P<strong>at</strong>rick R. Janiga<br />
Mr. Daniel R. Jesser<br />
Dr. and Mrs. Edward H. Jocoy<br />
Joe Pollak & Sons, Inc.<br />
Mr. and Mrs. Walter H. Johansson<br />
Ms. Joan L. Josephson<br />
Mrs. Ann E. Killian<br />
Mr. and Mrs. Jacky Knopp Jr.<br />
Mrs. Esther H. Koenig<br />
Mrs. Margaret Kowalski<br />
Ms. Laurie E. Krajna<br />
Mr. and Mrs. Herbert P. Ladds, Jr.<br />
Mr. Courtland R. LaVallee<br />
Mrs. K<strong>at</strong>hleen A. LaVictor<br />
Mrs. Aljean G. Leer<br />
Dr. and Mrs. Harold J. Levy<br />
Ms. Lenore Levy<br />
Mr. Joseph R. Luft<br />
Mr. and Mrs. David Macaluso<br />
Mr. and Mrs. Stephen Manes<br />
Dr. and Mrs. Paul V. Marrone<br />
Mrs. Joanne Marzullo<br />
Mrs. Santa M. Marzullo<br />
Mr. Robert D. Maslanka<br />
Dr. Irving J. Massey<br />
Mrs. Sarah G. Metzger<br />
Dr. and Mrs. Enrico Mihich<br />
Mr. Zachary J. Miknis<br />
Mrs. Darlene Miller<br />
Mrs. Naomi K. Mintzer<br />
Michael Timothy Moffit<br />
Dr. and Mrs. Phillip Moudy<br />
Mr. and Mrs. David R. Newcomb<br />
Dr. John Notaro<br />
Mr. and Mrs. James P. O'Brien<br />
Ms. Emily D. Paolini<br />
Mr. and Mrs. David M. Parish<br />
Dr. Edwin V. P<strong>at</strong>ricola<br />
Mr. and Mrs. David & Cindy M. Pecynski<br />
Mr. and Mrs. Richard M. Pirson<br />
Mr. and Mrs. Harvey Podolsky<br />
Mr. and Mrs. Edwin Presant<br />
Sen<strong>at</strong>or Mary Lou R<strong>at</strong>h<br />
Mrs. Edward L. Redmond<br />
Mr. and Mrs. Richard G. Riebling<br />
Mr. and Mrs. Robert S. Rochlin<br />
Mrs. Dean M. Rockwell<br />
Mr. and Mrs. Al Saia<br />
Ms. Ida Schaer<br />
Mr. and Mrs. Richard J. Schanley<br />
Dr. and Mrs. Ray G. Schiferle<br />
Mr. Walter R. Schoenfeld<br />
Mr. and Mrs. Joseph G. Scully<br />
Mr. and Mrs. Saunders M. Sennet<br />
Mr. and Mrs. Gust D. Servis<br />
Mr. Eugene M. Setel<br />
Dr. Russell N. Shefrin<br />
Mr. and Mrs. Walter S. Sikora<br />
Ms. Mary B. Sippel<br />
Mr. Abraham Slepian<br />
Dr. and Mrs. Edward H. Snell<br />
Mrs. Sylvia Sommerfield<br />
Ms. Geraldine Sonnesso<br />
Mr. and Mrs. Clarence E. Spitzer, Jr.<br />
Mr. and Mrs. Gerald R. Stafford<br />
Mr. and Mrs. Dean C. St<strong>at</strong>hacos<br />
Mr. and Mrs. Edmund D. Stevens, III<br />
Mr. and Mrs. Gerald R. Strauss<br />
Ms. Karen A. Szalkowski<br />
Mrs. Cecile Tegler<br />
Mr. and Mrs. William Dennis Toole<br />
Mrs. Constance S. Umland<br />
Mrs. P<strong>at</strong>ricia S. Utz<br />
Valley View Nurseries, Inc.<br />
Mr. and Mrs. John A. Vogel<br />
Mrs. Laura M. Walfrand<br />
Dr. and Mrs. James Warde<br />
Mrs. Marie A. Weber<br />
Mr. Raymond Weil<br />
Ms. Marie L. Weisbecker<br />
Dr. and Mrs. Robert M. Werner<br />
Mr. and Mrs. Douglas L. Winokur<br />
Mr. and Mrs. James Wise<br />
Dr. and Dr. Thomas S. Wiswall<br />
Mr. and Mrs. Marvin D. Wolfish<br />
Mr. and Mrs. Frederick S. Wood<br />
Mr. and Mrs. Martin S. Wright<br />
Mr. and Mrs. Jerome Zelasko, Jr.<br />
Mr. and Mrs. Harold A. Zimmer<br />
Mr. and Mrs. Randal C. Zimmer<br />
22 23
Recent Public<strong>at</strong>ions<br />
• Cody, V., Luft, J.R. & Pangborn, W. (<strong>2005</strong>). Understanding the role of Leu22 variants in methotrex<strong>at</strong>e resistance:<br />
Comparison of wild-type and Leu22Arg variant mouse and human dihydrofol<strong>at</strong>e reductase ternary crystal complexes<br />
with methotrex<strong>at</strong>e and NADPH, Acta Cryst. D61, 147-155.<br />
• Cody, V., Chisum, K., Pope, C. & Queener, S.F. (<strong>2005</strong>). Purific<strong>at</strong>ion and characteriz<strong>at</strong>ion of human-derived Pneumocystis<br />
jirovecii dihydrofol<strong>at</strong>e reductase expressed in Sf21 insect cells and in Escherichia coli, Protein Purific<strong>at</strong>ion and Expres<br />
sion, 40, 417-423.<br />
• Cody, V. (<strong>2005</strong>). Thyroid Hormone Structure-Function Rel<strong>at</strong>ionships. In Werner and Ingbar's The Thyroid: A Fundamental<br />
and Clinical Text, 9th edition, Braverman, L. E. & Utiger, R. D. (eds), Lippincott Williams & Wilkins Publishers, Philadel<br />
phia, pp. 151-157.<br />
• Davis, P.J., Davis, F.B. & Cody, V. (<strong>2005</strong>). Membrane receptors medi<strong>at</strong>ing thyroid hormone action, Trends in Endocrin.<br />
Metabol. 16, 429-435.<br />
• Ghosh, D. Three-dimensional structures of sulf<strong>at</strong>ases. Methods in Enzymology 400, 273-293 (<strong>2005</strong>)<br />
• <strong>Hauptman</strong>, H.A., Langs, D.A. & Xu, H. (<strong>2005</strong>). The phase problem in neutron crystallography. In Hydrogen and<br />
Hydr<strong>at</strong>ion-Sensitive Structural Biology, pp. 187-194, KubaPro Co. Ltd., Tokyo, Japan..<br />
• Judge, R.A., Snell, E.H. & van der Woerd, M.J. (<strong>2005</strong>). Extracting trends from two decades of microgravity macromo<br />
lecular crystalliz<strong>at</strong>ion history, Acta Cryst. D61, 763-771.<br />
• Lakhman S. S., Ghosh, D., Blanco, J. G. Functional significance of a n<strong>at</strong>ural allelic variance of human carbonyl reduc<br />
tase 3 (CBR3). Drug Metab. Dispos. 33, 254-257 (<strong>2005</strong>).<br />
• Langs, D.A., <strong>Hauptman</strong>, H.A. & Xu, H. (<strong>2005</strong>). Future prospects for the phase determin<strong>at</strong>ion of macromolecular<br />
structures from neutron d<strong>at</strong>a alone. In Hydrogen and Hydr<strong>at</strong>ion-Sensitive Structural Biology, pp. 207-212, KubaPro Co.<br />
Ltd., Tokyo, Japan.<br />
• Neumann, P., Cody, V. & Wojtczak, A. (<strong>2005</strong>). Ligand binding <strong>at</strong> the transthyretin dimer-dimer interface: structure of<br />
transthyretin-T4Ac complex <strong>at</strong> 2.2A resolution, Acta Cryst. D61, 1313-1319.<br />
• Pletnev, V. & Duax, W. L. (<strong>2005</strong>). R<strong>at</strong>ional proteomics IV. Modeling the primary function of the mammalian 17hydroxysteroid<br />
dehydrogenase type 8, J. Steroid Biochemistry & Molecular Biology, 94, 327-335.<br />
• Smith, G,D., Pangborn, W.A. & Blessing, R.H. (<strong>2005</strong>). The structure of T6 bovine insulin, Acta Cryst., D61, 1476-1482.<br />
• Snell, E.H. & Helliwell, J.R. (<strong>2005</strong>). Macromolecular crystalliz<strong>at</strong>ion in microgravity, Reports on Progress in Physics, 68,<br />
799-853.<br />
• Snell, E.H., van der Woerd, M.J., Miller, M.D. & Deacon, A.M. (<strong>2005</strong>). Finding a cold needle in a warm haystack:<br />
Infrared imaging applied to loc<strong>at</strong>ing cryocooled crystals in loops, J. Appl. Cryst. 38, 69-77.<br />
• Thomas, J.L., Boswell, E.L., Scaccia, L.A., Pletnev, V. & Umland, T.C. (<strong>2005</strong>). Identific<strong>at</strong>ion of key amino acids responsible<br />
for the substantially higher affinities of human type 1 3-hydroxysteriod dehydrogenase/isomerase (3-HSD1) for<br />
substr<strong>at</strong>es, coenzymes and inhibitors rel<strong>at</strong>ive to human 3-HSD2, J. Biol. Chem. 280, 21321-21328.<br />
• Wang, Y.Z., Feng, L., Said, M., Balderman, S., Liu, Y., Ghosh, D. & Gulick, A. M. (<strong>2005</strong>). Analysis of the 2.0Å crystal<br />
structure of the protein-DNA complex of the human PDEF Ets domain bound to the prost<strong>at</strong>e specific antigen regul<strong>at</strong>ory<br />
site. Biochemistry 44, 7095-7106.<br />
• Xu, H., <strong>Hauptman</strong>, H.A. & Langs, D.A. (<strong>2005</strong>). Novel st<strong>at</strong>istical approach to the phase problem in neutron crystallogra<br />
phy. In Hydrogen and Hydr<strong>at</strong>ion-Sensitive Structural Biology, pp. 197-205, KubaPro Co. Ltd., Tokyo, Japan.<br />
• Xu, H., Weeks, C. M. & <strong>Hauptman</strong>, H. A. (<strong>2005</strong>). Optimizing st<strong>at</strong>istical Shake-and-Bake for Se-<strong>at</strong>om substructure<br />
determin<strong>at</strong>ion, Acta Cryst. D61, 976-981<br />
24
The <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong><br />
Celebr<strong>at</strong>ing fifty years of basic research in the biosciences ...<br />
dedic<strong>at</strong>ed to furthering science for the next fifty years and beyond ...<br />
Select Awards and Honors In Recognition of Our New Building<br />
The <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong> is celebr<strong>at</strong>ing 50 years<br />
of groundbreaking research and beginning the next fifty years in our one-year<br />
old home. Our new st<strong>at</strong>e-of-the-art facility gives us room to grow – growth th<strong>at</strong><br />
will occur by recruiting new talent to Western New York. Our scientists are<br />
striving to achieve gre<strong>at</strong>er scientific understanding and to educ<strong>at</strong>e the young<br />
scientists of the future.<br />
<strong>2005</strong> Brick by Brick Award<br />
Best Medical Complex<br />
Architectural Engineering Award <strong>2005</strong><br />
N<strong>at</strong>ional Associ<strong>at</strong>ion of Industrial and Office Properties<br />
The American <strong>Institute</strong> of Architects <strong>Buffalo</strong><br />
WNY Chapter, First Award<br />
New Construction > 25,000 s.f.<br />
President’s Message ……………………..………………………………......1<br />
Chief Executive Officer’s Message …………………................................ 2<br />
A Historical Perspective – 50 Years of Finding Cures ............................. 3<br />
The Future – Forging Into The Next 50 Years …….………..……………... 9<br />
The Science <strong>at</strong> the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong> .... 13<br />
The People of the <strong>Hauptman</strong>-<strong>Woodward</strong> Medical Research <strong>Institute</strong> ….. 18<br />
Financial Summary ……………………………………………………….. 20<br />
Donor Highlights ………………………………………………………..... 21