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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

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