Division of Basic Sciences annual research directory

922 Pages·1996·56.5 MB·English

by  National Cancer Institute (U.S.). Division of Basic Sciences

Center for Cancer Research
Annual Research Directory 2002
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Cover: Center: Bovine papillomavirus fully bound by
neutralizing monoclonal antibody #9 as seen in a 3D image
reconstruction ofcryoelectron micrographs. The complex is
viewed down a five-fold axis ofsymmetry. The density due
to the antibody is shown in red and the density ofBPV1 is
shown in blue.
John Schiller, Laboratory of Cellular Oncology; and
Benes Trus, Center for Information Technology
Left, from top to bottom: 3D characterization ofthe
prostate gland by coregistering whole-mountstep section
MR
histopathology; anatomic image; color-encoded
Dynamic Contrast Enhanced MR! (DEMRI) depicting areas
ofvascularperfusion andpermeability; andplot ofsignal
intensity over time from prostate cancer.
C. Norman Coleman and Cynthia Menard, Radiation
Oncology Branch; Peter Choyke and Michael Knopp, Clinical
Center/Diagnostic Radiology Department; reprintpermission
for the whole-mountstep section histopathology obtained
from Nature and from Cole KA, Krizman DB, and
—
Emmert-Buck MR. The genetics ofcancer a 3D model.
Nature Genetics Supplement 1999;21:38-41.
—— ————————————————————————— ———————— ——— —
1
Contents
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1 Office of the Director J. Carl Barrett, Ph.D.
9 Office of the Clinical Director Gregory Curt, M.D.
Branches
1 Cancer Prevention Studies Branch Philip R. Taylor, M.D., Sc.D.
25 Cancer Therapeutics Branch Sandra M. Swain, M.D.
39 Cell and Cancer Biology Branch Kathleen Kelly, Ph.D.
65 Dermatology Branch Mark C. Udey M.D., Ph.D.
79 Experimental Immunology Branch Alfred Singer, M.D.
105 Experimental Transplantation and Immunology Branch Ronald E. Gress, M.D.
123 Genetics Branch IIan R. Kirsch, M.D.
143 HIV and AIDS Malignancy Branch Robert Yarchoan, M.D.
161 Medical Oncology Clinical Research Unit Ronald E. Gress, M.D.
175 Metabolism Branch Thomas A. Waldmann, M.D.
199 Neuro-Oncology Branch Howard Eine, M.D.
205 Pediatric Oncology Branch Lee J. Helman, M.D.
235 Radiation Biology Branch James B. Mitchell, Ph.D.
—
245 Radiation Oncology Branch C. Norman Coleman, M.D.
259 Surgery Branch Steven A. Rosenberg, Ph.D., M.D.
—
289 Urologic Oncology Branch 1/1/ Marston Linehan, M.D.
Laboratories
297 Basic Research Laboratory-Bethesda Douglas R. Lowy M.D.
331 Basic Research Laboratory-Frederick Robert H. Wiltrout, Ph.D.
361 Laboratory of Biochemistry Claude Klee, M.D.
385 Laboratory of Biosystems and Cancer J. Carl Barrett, Ph.D.
395 Cancer and Developmental Biology Laboratory Colin L. Stewart, D.Phll.
403 Laboratory of Cell Biology Michael M. Gottesman, M.D.
421 Laboratory of Cell Regulation and Carcinogenesis Anita B. Roberts, Ph.D.
433 Laboratory of Cellular and Molecular Biology Lawrence E. Samelson, M.D.
443 Laboratory of Cellular Carcinogenesis and Tumor Promotion
Stuart H. Yuspa, M.D.
461 Laboratory of Cellular Oncology Douglas R. Lowy, M.D.
477 Laboratory of Comparative Carcinogenesis Larry K. Keefer, Ph.D.
493 Laboratory of Experimental and Computational Biology Jacob V. Maizel, Ph.D.
515 Laboratory of Experimental Carcinogenesis Snorri S. Thorgeirsson, M.D., Ph.D.
525 Laboratory of Experimental Immunology John R. Ortaldo, Ph.D.
537 Gene Regulation and Chromosome Biology Laboratory
Jeffrey N. Strathern, Ph.D.
553 Laboratory of Genetics Michael Potter, M.D.
563 Laboratory of Genomic Diversity Stephen J. O'Brien, Ph.D.
577 Laboratory of Human Carcinogenesis Curtis C. Harris, M.D.
585 Laboratory of Immune Cell Biology Jonathan D. Ashwell, M.D.
591 Laboratory of Immunobiology Berton Zbar, M.D.
599 Macromolecular Crystallography Laboratory Alexander Wlodawer, Ph.D.
611 Laboratory of Medicinal Chemistry Victor E. Marguez, Ph.D.
625 Laboratory of Metabolism PrankJ. Gonzalez, Ph.D.
637 Laboratory of Molecular Biology Ira Pastan, M.D.
— ———— — —
Laboratories (continued)
665 Laboratory of Molecular Cell Biology Carl Wu, Ph.D.
—
669 Laboratory of Molecular Immunoregulation JoostJ. Oppenheim, M.D.
687 Laboratory of Molecular Pharmacology Yves Pommier, M.D., Ph.D.
701 Laboratory of Pathology Lance Liotta, M.D., Ph.D.
741 Laboratory of Population Genetics Kenneth Buetow, Ph.D.
751 Laboratory of Receptor Biology and Ge—ne Expression Gordon L. Hager, Ph.D.
765 Regulation of Cell Growth Laboratory Karen H. Vousden, Ph.D.
—
779 Regulation of Protein Function Laboratory Allan Welssman, M.D.
785 Structural Biophysics Laboratory R. Andrew Byrd, Ph.D.
795 Laboratory of Tumor Immunology and Biology Jeffrey Schlom, Ph.D.
Programs
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807 AIDS Vaccine Program Larry 0. Arthur, Ph.D.
—
821 Computational Applications Program Stanley K. Burt, Ph.D.
—
825 HIV Drug Resistance Program John M. Coffin, Ph.D.
—
829 Resistance Mechanisms Laborato—ry Stuart F. J. Le Grice, Ph.D.
835 Retroviral Replication Laboratory Stephen H. Hughes, Ph.D.
—
845 Molecular Targets Drug Discovery Program Michael Boyd, Ph.D.
847 Mouse Cancer Genetics Program—A/ea/ G. Copeland, Ph.D.
Administrative Resource Centers
859 Building 10A
861 Building 10B
862 NCI-Frederick
863 Building 37
864 Building 41
865 IT Administrative Resource Center
867 Appendix A: Areas of Expertise by Investigator
871 Appendix B: NCI Faculties and Faculty Web Sites
873 Appendix C: Core Facilities and Resources
879 Appendix D: 2002 Intramural Research Award and
Collaborative Project Award Recipients
881 Appendix E: Board of Scientific Counselors-A
883 Appendix F: Board of Scientific Counselors-B
885 Alphabetical Investigator Index
889 Keyword Index
901 Clinical Trials Index
1
Office of the Director
Center for Cancer Research
J. CarlBarrett, Ph.D.
Directorofthe Center for Cancer Research, NCI
Building 31
Room 3A1
Phone [phone]
Fax [phone]
E mail [email protected]
Biography: Dr Barrettreceivedhis B.5. in chemistryat William and Mary College,
Williamsburg, \/A, in 1969 and his Ph.D. in biophysical chemistryatJohns Hopkins
University, Baltimore, MD, in 1974. Following a 3-yearpostdoctoral fellowship atJohns
Hopkins University, Dr. Barrettbegan his careerat the NationalInstitute ofEnvironmental
Health Sciences as leaderofthe Environmental Carcinogenesis Group, Laboratoryof
PulmonaryPathoblology. In 1987, he became chiefofthe Laboratory ofMolecular Carcinogenesis where he conducted
research on critical targetgenes In carcinogenesis molecularmechanisms ofenvironmentallyInduced cancers. His current
research is centered on the relationship between aging and cancer, the genes involvedin cellularsenescence and
differentiation, and the function ofKAI-1 and othercancermetastasissuppressorgenes. He is editor-in-chiefofMolecular
Carcinogenesis, associate editorofCancer Research, anda memberofthe editorialboards of 12journals. He has been a
chairperson, organizer, orkeynotespeakerat various conferences, workshops, andsymposia and has authored or
coauthored over400publications.
C. Norman Coleman, M.D.
Deputy Director, CCR
Building 10
Room B3B69
Phone [phone]
Fax [phone]
E mail [email protected]
Biography: Dr. Coleman graduated from the University of Vermont with a B.A. In
theoretical mathematics, then graduated from Yale UniversitySchool ofMedicine in
1970. He completed his Internship andresidencyIn Internalmedicine at the Universityof
California In San Erancisco andat the NCI. Board-certifiedIn internal medicine, medical
oncology, andradiation oncology. Dr. Coleman was a tenured facultymemberofthe
Departments ofRadiologyand Medicine at the Stanford UniversitySchool ofMedicine beforejoining Harvard Medical
Schoolin 1985asprofessorand chairman oftheJoint Center for Radiation Therapy. In 1999, he came to the NCIand
became directorofthe new Radiation OncologySciences Program thathe created to coordinate radiation oncology
activities within the NCI. He also serves the NCIas chiefofthe Radiation Oncology Branch, deputy directorofthe Center
for Cancer Research, associate directorofthe Radiation Research Program, andspecialadvisor to the directorofthe NCI.
He has written extensivelyin his fieldand has won numerous awards.
1
Lee Helman, M.D.
J.
Deputy Director, CCR
Building 10
Room 13N240
Phone [phone]
Fax [phone]
E mail [email protected]
Biography: Dr. Helman receivedhis M.D. magna cum laude in 1980 from the University
ofMarylandSchool ofMedicine. He completed his clinical training In Internalmedicine at
Barnes Hospital, Washington University, in 1983, andin medical oncologyat the NCI
Pediatric OncologyBranch and Medicine Branch In 1986. He has heldpositions of
increasing responsibilityat the NCIandbecame branch chiefIn 1997. Dr. Helman has a
wide range ofresearch Interests andaccomplishmentsspanning moleculargenetics ofhuman cancerand development of
new therapeuticapproaches topediatricsolid tumors.
Douglas R. Lowy, M.D.
Deputy Director, CCR
Building 36
Room 1D32
Phone [phone]
Fax [phone]
E mail [email protected]
Biography: Dr. Lowyreceivedhis M.D. from New York UniversitySchool ofMedicine In
1968. Between 1970 and 1973, he was a research associate In the LaboratoryofViral
Diseases, NationalInstitute ofAllergyandInfectious Diseases, NIH. He trainedin Internal
medicine atStanford Universityand dermatologyat Yale University, andstartedhis
laboratoryat the NCI in 1975. He has been chiefofthe LaboratoryofCellular Oncology
since 1983 anda deputydirectorsince 1996. He has received the Wallace RoweAward for Virus Research andhas been a
memberofmanyscientificadvisoryboards, grants committees, and editorialboards.
Robert H. Wiltrout, Ph.D.
Deputy Director, CCR
Building NCI-Frederick 428
Room 46
Phone [phone]
Fax [phone]
E mail [email protected]
Biography: Dr. Robert Wiltroutobtainedhis Ph.D. in immunology from Wayne State
University In 1979 andperformedpostdoctoralstudies on the regulation ofimmune
responses with Dr. Ronald Herberman at the NCI. Hejoined the Laboratoryof
ExperimentalImmunologyandbecame head ofthe Experimental Therapeutics Section in
1986. Dr. Wiltrouthas also servedas chiefofthe Basic Research Laboratorysince 1999.
He has been a memberofmanyscientificadvisoryboards, extramural reviewgroups, and editorial boards.
2
—
Stuart H. Yuspa, M.D.
Deputy Director, CCR
Building 37
Room 3B25
Phone [phone]
Fax [phone]
E mail [email protected]
Biography: Dr. Yuspa received his B.5. fromJohns Hopkins Universityand his M.D. from
the University ofMaryland MedicalSchool. He completed his internship and residencyat
the Hospital ofthe UniversityofPennsylvania and has been a seniorinvestigatorat the
NCIsince 1972. Among his honors are the Lila GruberAward oftheAmerican Academy
ofDermatologyand the ClowesAward from theAmerican Association for Cancer
Research. Dr. Yuspa is the authorofmore than 300publications In the fields ofcarcinogenesis and epithelial
differentiation.
Introduction
The NCTs Center for Cancer Research (CCR) was created in March 2001 by
merging two vital components ofthe NCTs Intramural Research Program
the Division of Basic Sciences (DBS) and the Division of Clinical Sciences
(DCS). This merger, initiated by former NCI Director Dr. Richard Klausner, is
an important step in our goal to promote closer links between basic
researchers and clinical investigators, thereby enhancing their opportunities
for both scientific discovery and translational research (bench-to-bedside and
bedside-to-bench). The CCRis also committed to supporting and training
young scientists and clinicians as they launch their careers inbasic and
clinical research. CCRoffers numerous predoctoral, postdoctoral, and clinical
training positions with world-class scientists and physicians who are
outstanding mentors and experts in their respective fields.
The CCRis composed of over 300 principal investigators in 54 laboratories,
branches, and programs. As one of the world's largest cancer research
centers, the CCR takes advantage of the breadth of its researchers' training
and experience to foster interdisciplinary programs and facilitate translational
research. Basic research is a strength of the CCR, with areas of investigation
including: immunology; carcinogenesis; human genetics; mouse genetics;
DNA
viral oncology; HIV; chromatinbiology; structuralbiology; replication
and recombination; signal transduction; apoptosis; cell cycle regulation;
cytokines and chemokines; cellular, molecular, and developmental biology;
medicinal chemistry and natural products chemistry; molecular pharma-
cology; xenobiotic metabolism; radiation biology; computational biology; and
bioinformatics. Areas of excellence in clinical and translational research
include: cancer vaccines, clinical proteomics, molecular targets of cancer,
molecular imaging, biologic mediators, cell-based therapies, immunotoxin
therapy, radiation therapy, cancer genetics, molecular epidemiology, cancer
prevention, multidrug resistance, clinical pharmacology, angiogenesis, and
molecular pathology. The CCRWeb site at http://ccr.nci.nih.gov offers
detailed descriptions of thebasic research and clinical programs as well as
links to current CCR clinical trials. The Newsletter and CCR Press section
highlight some of the latest published findings from the Center.
3
New Scientific Opportunities in Interdisciplinary and Translational Research
The CCR mission is to reduce the burden of cancer through exploration,
discovery, and translation. The goals of the NCTs restructuring with the creation
of the Center for Cancer Research are:
• to foster interdisciplinary research
• to facilitate translational research
• to expedite technology development
• to eiiliance training, particularly in interdisciplinary and translational
research, and
• to build partnerships between NCI and other NIH Institutes, federal agencies,
academia, biotechnology companies, and the pharmaceutical industry
The CCR along with the Division of Cancer Epidemiology and Genetics (the
other NCI intramural division) has defined new institutional approaches to
translate scientific knowledge towards achieving more effective cancer
prevention, intervention, and treatment. The goal is to create an integrated,
multidisciplinary research environment thatbrings together scientists from
diverse fields to work on translating basic research findings into clinical
applications. Collaboration, technology support and development, and access to
resources are critical to achieving this goal. The NCI has responded to this
challenge by establishing Faculties, which are composed of scientists from
diverse laboratories and branches working cooperatively with a common
interest in a particular discipline, disease, or approach to scientific discovery.
Faculties foster collaboration, open access to new technologies and clinical
resources, and challenge NCI researchers to become more involved in clinical
research. Within the past year the following Faculties were established:
• Molecular Targets
• Immunology
• Epidemiology, Carcinogenesis, and Prevention
• Chemistry and Structural Biology
• Cellular, Molecular, and Developmental Biology
• Genetics, Genomics, and Proteomics
• Breast Cancer
• Gynecologic Oncology
• Genitourinary Malignancies
• HIV and Cancer Virology
• Bioinformatics, Biostatistics, and Computational Biology
Faculties provide a forum for scientists to engage one another to promote
interaction and communication. Their goals are to promote translational and
interdisciplinary research; to develop new technologies and resources; to
enhance mentoring, recruitment, and training of fellows; to improve
communication through retreats and seminars; to sponsor visiting scientists; to
provide strategic planning and oversight; and to advise NCI leadership on
important and innovative programs critical to the success of the NCI Intramural
Program. Visit the Faculties Web site at http://ccr.nci.nih.gov for additional
information and updates on their activities.
The Medical Oncology Clinical Research Unit (MOCRU) was recently
established to enhance the medical oncology clinical infrastructure and to
enhance clinical investigation within the CCR. The MOCRU is a group of
dedicated physicians who conduct clinical studies on a specific disease or
MOCRU
therapeutic area as a team effort. The is composed of Clinical Research
Sections in breast cancer, genitourinary/gynecologic malignancies, vaccines,
lymphoma, transplantation, immunotherapy, AIDS malignancies,
lung/gastrointestinal cancer, and clinical genetics. Institutional support for the
program is also provided through a Phase I Clinical Research Section, scientific
core services, and offices for clinical operations, protocol support, research
nurses, nurse practitioners, physicians' assistants, fellowship training,
MOCRU
translational research, and Navy-Oncology. The mission of the is to
provide access to clinical research across the Center, excellence in clinical care,
clinical training opportunities, and career growth for clinical staff.
Technology Development and Support
Technology development and support is yet another important goal of the CCR
intramural program. Technology initiatives currently under development
include clinical proteomics, molecular targets drug discovery, microarray
technology, animal models development, and imaging tedmologies. The
proteomics initiative involves the search for new serum markers for cancer;
development of antibody chips, protein arrays, and reverse phase chips; a mass
spectrometry center; a protein expression laboratory; and bioinformatics
support. The molecular targets drug discovery program provides a full range of
drug discovery scientific support: advising scientists on molecular target
discovery, development of screening assays, conducting screens ofpure
compound libraries, validation ofhits, and assistance in preclinical and clinical
development ofpromising lead compounds. The microarray initiative uses
modern lab automation and robotic methods for the production of gene
microarrays to allow simultaneous study of the differential expression of large
numbers of genes in normal, diseased, or treated cells. The animal models
initiative includes transgenic and knockout core services, molecular and
comparative pathology support, mouse proteomics, rodent imaging,
phenotyping core support, and an animal brain tumor therapeutic and
diagnostic core. The imaging initiative incorporates clinical imaging, advanced
imaging applications, experimental and innovative technologies, and animal
imaging into an interrelated imaging resources program. The CCRWeb site at
http://ccr.nci.nih.gov features an initiatives section with additional details,
contact information, and the latest projects.
Mentoring and Training
The CCR places a particular emphasis on training the next generation of
investigators inbasic, interdisciplinary, and translational cancer research.
Programs offered in the CCR include ACGME-accredited residency programs in
anatomic pathology, radiation oncology, and dermatology. Additionally,
ACGME
clinical fellowship training programs in medical oncology, pediatric
hematology/oncology, hematology/pathology, and cytology/pathology are
available. Fellowships programs in surgical oncology, urological oncology,
neuro-oncology, HIV and AIDS malignancy, gynecologic oncology, clinical
cancer research for Ph.D.s, cancer epidemiology, cancer genetics, and cancer
A
prevention are also offered. Senior Clinical Research Fellowship is offered to
outstanding clinical fellows to allow a period of intense training in translational
research. The Center is involved in the Graduate Program Partnership initiative
5
tliat was recently established to attact graduate students to CCR laboratories.
Areas of partnership currently under development include bioinformatics,
chemistry, and comparative pathology. The Cancer Research Training Award
(CRTA) and the Visiting Fellows (VF) program for foreign trainees are available
in all the laboratories, branches, and programs. Visit the Web site for career and
training opportunities.
Partnerships with Academia and Industry
The CCR is committed to forming partnerships that encourage technology
development with industry, academia, and the private sector. CCR scientists and
clinicians have a history of successful research collaborations with colleagues
nationally and internationally. The CCR is also active in the area of technology
transfer and strives to ensure that scientific breakthroughs reach the public
through formal agreements between the government and industry. During the
last year, there were over 100 active Collaborative Research and Development
Agreements (CRADAs) between CCR investigators and outside institutions. For
further information, contact the CCROffice of Research and Technology
Partnerships at http://ccr.nci.nih.gov.
Unique Aspects of the Intramural Research Program
Thejuxtaposition ofbasic and clinical researchers in this large, diverse, yet
highly interactive Center provides exceptional translational research and
training opportunities. With the resources available at the NIHClinical Center,
which houses over 50 percent of the NIH-funded general clinical research center
beds in the United States, CCR scientists have a unique environment enabling
them to move new drugs and diagnostics quickly from thebench to the bedside.
Medical care is provided without charge to patients enrolled on NCI protocols.
In addition, patients' travel is covered, and for children and minors participating
in intramural studies, travel is also provided for a parent or guardian. One goal
of the CCR is to capitalize on this extraordinary clinical resource.
The CCR is a center of excellence for vaccine development and cell-based cancer
immunotherapies utilizing specialized expertise, techniques, and facilities that
exist within the Intramural Program. An example of the uniqueness of the
Intramural Program is seen in the basic and clinical proteomics initiative, which
is a collaboration between the NCI and the FDA. The program is built on laser
capture microdissection technology, developed in the CCRLaboratory of
Pathology, which involves identification and extraction ofmicroscopic
homogenous cellular subpopulations from surrounding tissue. This technology
is now being used to isolate tumor versus normal cellular subpopulations to
identify potential molecular targets for cancer therapies. The long-range
commitment needed to develop the technology to accurately identify specific
targets for various cancers requires support that is unique to the Intramural
Research Program. Another component ofthe proteomics initiative is the
identification ofnovel markers for early cancer detection.
These types of long-term, high-risk projects can accelerate the pace ofmedical
research with public health importance and have an immeasurable impact on
improving the nation's health care.