Appendix A
Overview and Description Lucille P. Markey Charitable Trust Research Program Grants Awards

OVERVIEW AND DESCRIPTION RESEARCH PROGRAM GRANTS

University of Texas, Southwestern Medical Center ($2,280,000 • 1986-1992). The grant provided support of the research program of Joseph Goldstein and Michael Brown in molecular genetics and genetic diseases. Research focused on understanding the control of transcription at the molecular level and the behavior of the receptor at the whole-animal level. Most funding was utilized for equipment and supplies to support pilot projects and to explore new areas of research (includes $1,155,000 in supplemental funding awarded in 1988 and $300,000 awarded in 1991).


Carnegie Mellon University ($1,925,000 • 1986-1991). The grant provided funds for research on spectroscopy in the biomedical sciences. Research was concentrated into two areas: (1) biomedical nuclear magnetic resonance (NMR) in collaboration with the organ transplant surgeons at the University Pittsburgh School of Medicine and (2) a program on X-ray crystallography of biological macromolecules. Funds were combined with the National Institutes of Health (NIH) and National Science Foundation (NSF) funds in support of the new NMR Center for Biomedical Research. In addition, some funding was applied to faculty and graduate student support. Chien Ho was the principal investigator (PI).


Stanford University ($12,613,550 • 1988-1996). The grant provided support for the Center for Molecular and Genetic Medicine and established



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Funding Biomedical Research Programs: Contributions of the Markey Trust Appendix A Overview and Description Lucille P. Markey Charitable Trust Research Program Grants Awards OVERVIEW AND DESCRIPTION RESEARCH PROGRAM GRANTS University of Texas, Southwestern Medical Center ($2,280,000 • 1986-1992). The grant provided support of the research program of Joseph Goldstein and Michael Brown in molecular genetics and genetic diseases. Research focused on understanding the control of transcription at the molecular level and the behavior of the receptor at the whole-animal level. Most funding was utilized for equipment and supplies to support pilot projects and to explore new areas of research (includes $1,155,000 in supplemental funding awarded in 1988 and $300,000 awarded in 1991). Carnegie Mellon University ($1,925,000 • 1986-1991). The grant provided funds for research on spectroscopy in the biomedical sciences. Research was concentrated into two areas: (1) biomedical nuclear magnetic resonance (NMR) in collaboration with the organ transplant surgeons at the University Pittsburgh School of Medicine and (2) a program on X-ray crystallography of biological macromolecules. Funds were combined with the National Institutes of Health (NIH) and National Science Foundation (NSF) funds in support of the new NMR Center for Biomedical Research. In addition, some funding was applied to faculty and graduate student support. Chien Ho was the principal investigator (PI). Stanford University ($12,613,550 • 1988-1996). The grant provided support for the Center for Molecular and Genetic Medicine and established

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Funding Biomedical Research Programs: Contributions of the Markey Trust the Department of Developmental Biology. Research focused on examining how the complex multicellular structures of the adult organism result from the fertilized egg. Funding was equally divided among faculty salaries, equipment, and supplies, and other administrative costs. Lucy Shapiro was the PI. California Institute of Technology ($12,500,0001 • 1986-1997). The grant supported expansion of the Developmental Biology Center by attracting new faculty, upgrading instrumentation, and creating an intramural research funding program. About one-half of the grant was used to support internal grant programs—modest, multiyear innovative research—and one-third was used to support multiuser facilities and instrumentation. Leroy Hood and Eric Davidson were the PIs. University of Chicago ($8,719,2231 • 1986-1997). The grant supported an integrated program of research in neurosciences, emphasizing neurobiology and neuroimmunology. Funding was used to recruit new faculty and to renovate and equip laboratory space. Funds were equally divided among salaries, equipment, renovation, and a residual category of core support, supplies, and overhead. Samuel Hellman was the PI. The Whitehead Institute for Biological Research ($7,150,0002 • 1988-1996). The grant supported a program in developmental biology. Funding was used to support a number of young faculty and postgraduate students. Faculty were provided salary support and lab space with associated setup costs. About 20 percent of the grant was used for core renovations and equipment. David Baltimore was the PI, followed by Gerald Fink. Washington University in St. Louis ($12,100,000 • 1988-1994). The grant established the Markey Center for the Study of Molecular Biology and Human Disease within the Department of Genetics. Four funding priorities were established: competitive research support, faculty recruitment, core research support, and equipment and instrumentation. The majority of funding was for faculty research support, with a significant amount of funding for equipment and core support. Daniel Hartl was PI, followed by Emil Unanue. 1   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators addressing important problems in biomedical sciences awarded in FY 1996. 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust Harvard Medical School ($11,000,000 • 1988-1993). The grant provided support to establish a program in molecular and cellular basis of development. The program resulted from the merging of several departments and received considerable intramural support. Funding was used for faculty salaries, technical and staff support, supplies, equipment, and facility renovation. Daniel Tosteson was the PI. University of California, Los Angeles. ($4,350,0002 • 1988-1997). The grant established the Lucille P. Markey Program in Cellular Biochemistry in the Department of Biological Chemistry. The program investigated the transport of proteins in cells and genetic regulation of the early development of higher organisms Funds were used for (1) faculty support; (2) stipends for graduate students and postdoctoral fellows; (3) renovation, equipment, and supplies; and (4) a series of symposia in cellular biology. Elizabeth Neufield was the PI. Yale University ($12,100,000 • 1988-1997). The grant provided support for the program in molecular oncology at the Yale Center for Molecular Medicine, which became the Boyer Center. Funding was provided for faculty support, a clinical scholars program, supplies and services, core facility, equipment, and fellowships. Sherman Weissman and Vincent Marchesi were the co-PIs. University of Oregon ($3,300,000 • 1988-1995). The grant provided funds to establish a Center for Macromolecular Assemblies in Cell Biology combining research in three-dimensional macromolecular structures utilizing crystallographic techniques, macromolecular thermodynamics, and macromolecular interactions. Markey funds were supplemented by those from NSF and NIH. In addition to major equipment purchases and lab support, funding was used for faculty support, recruiting, visits, seminar speakers, and support personnel. Brian Matthews was the PI. University of Wisconsin ($990,000 • 1988-1992). The grant provided funding for support of studies of molecular biophysics and molecular genetics. Funding was used for the support of research associates, including several graduate students, working with principal investigators. The co-PIs were Barry Ganetzky, Julis Adler, and Ching Kung. 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust University of Texas, Southwestern Medical Center ($1,045,000 • 1988-1994). The grant provided funding for a study on receptor G-protein systems by the Department of Pharmacology. The grant funded a number of postdoctoral fellows, supplemented faculty salaries, and was used for supplies. Alfred Gilman was the PI. University of Pennsylvania ($4,220,4021 • 1988-1997). The grant funded molecular genetic approaches to define the mechanisms and treatment of disease. This program was a joint project of the Schools of Medicine and Veterinary Medicine. Funding was used for salaries, supplies, equipment, renovation, and animal care or purchase. Mark Green and Donald Patterson were PIs. (Includes $370,402 in supplemental funding awarded in 1994.) University of Miami ($6,770,000 • 1988-1998). The grant provided funds to enhance research efforts in the Department of Biochemistry and Molecular Biology. Initially, funding was used for the completion of shell laboratory space and for recruitment of a new department chairman. Because of recruiting difficulties the grant was put on hold until 1995 when a chair and five new faculty were recruited. Markey funds provided salary and start-up costs for these new faculty. Murray Deutscher was the PI. (Includes supplemental funding of $500,000 to support an endowed chair in biochemistry and microbiology.) Brandeis University ($3,200,0002 • 1988-1996). The grant supported the structural biology and biochemistry program and the mechanistic enzymology program. The research investigated the essential link between structural biology and biochemistry and determined the organization of the macromolecular assemblies that constitute living structures. The grant provided faculty support, graduate student stipends, and major equipment purchases. Gregory Petsko was the PI. (Includes $500,000 in supplemental funding awarded in 1990.) University of California, San Diego ($4,320,0002 • 1988-1998). The grant funded a project to support the study of cell growth and differentiation with an emphasis on the role of protein kinesis. Funding supported the 1   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators addressing important problems in biomedical sciences awarded in FY 1996. 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust research of seven established professors in the Division of Endocrinology and Metabolism. The PI was Gordon Gill. (Includes $300,000 in supplemental funding awarded in 1994.) Carnegie Institution of Washington ($2,700,0002 • 1988-1997). The grant supported studies on the molecular basis of gene expression. It enabled interdisciplinary research in the Department of Embryology on what activates one set of genes in one cell and what keeps these same genes repressed in another specialized cell. Funds were used primarily for the support of established investigators, stipends for postdoctoral fellows, and for major equipment and supply purchases. Donald Brown was the PI. Case Western Reserve University ($5,500,000 • 1988-1997). Funds supported the establishment of the Center for Developmental Genetics in the School of Medicine. The major emphasis of the center was the application of new techniques of molecular genetics to developmental biology. The center had three foci: studies on early embryogenesis in Drosophila, developmental neurobiology, and application of new molecular biology to understand developmental processes in the mouse. Funding was applied to faculty salaries, stipends for fellows, and major equipment. The PI was Huntington Willard. The Children’s Hospital, Boston ($2,475,000 • 1988-1993). The grant provided support for the Pulmonary Physiology Department and integrated pulmonary physiology with molecular biology and developmental biology. The mission of the lab was to study the transport defect in cystic fibrosis, the role of macrophages in inflammatory processes in the lung, errors in the synthesis of surfactant proteins, and the regulation of the pulmonary matrix. David Nathan was the PI. University of Michigan ($8,250,000 • 1988-1997). The grant provided funding to increase understanding at the molecular level of neurotransmitters in the brain. The grant supported 10 research projects for individual faculty ranging from molecular biology of receptor signal transduction to behavioral genetics to regulation of nicotinic acetylcholine receptor expression and six core projects. The goal was to determine the manner in which proteins are inserted into membranes and the environ- 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust ment and physiological effects of their activation. Sid Gilman and B. W. Agranoff were the PIs. The Neurosciences Institute ($1,375,000 • 1988-1995). Funding supported the institute’s theoretical neurobiology research program, whose goal was to understand how perception, memory, and other aspects of higher brain function are manifested as a result of elementary activity in the nervous system. The grant supported fellows in theoretical neuroscience, conferences, and summer programs. Research topics included visual perception and cortical mechanisms, mechanisms of synaptic modulation, and selective automata. The PI was Gerald Edelman. Columbia University ($6,500,000 • 1988-1996). The grant supported the development of the Center for Molecular Toxicology and Nutrition. The center’s coordinated investigation of the basic biological processes that underlie cancer, cardiovascular diseases, heritable genetic disease, and reproductive disorders. Research goals included (1) study of the cellular and molecular mechanisms of carcinogenesis due to chemicals; (2) reproductive and genetic toxicology; (3) study of nutritional factors linked to disease, especially atherosclerosis; and (4) molecular epidemiology. Funds were used for a major renovation and for salaries or stipends. Bernard Weisman was the PI. Purdue University ($6,990,0002 • 1988-1996). The grant supported the Center for Molecular Structure. The center utilized the university’s supercomputer to determine the atomic structures of viruses and membrane proteins with the ultimate objective of identifying cell receptors involved in the binding of viruses and antibodies. Funding was used for expansion of the Purdue structural biology faculty, graduate student and postdoctoral support, equipment, and salary for a visiting senior scholar each year. Michael Rossman was the PI. Eleanor Roosevelt Institute for Cancer Research ($1,475,000 • 1988-1993). The grant supported the study of somatic cell genetics and recombinant DNA and molecular understanding of human diseases and studies on mutagenesis, with emphasis on the mechanisms by which cyclic AMP (adenosine monophosphate) reverses malignant change in cells under certain conditions. Topics for studies included genome exposure theory, 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust mutation, differentiation, gene mapping, and genetic biochemistry. The majority of funding was used for salaries. Theodore Puck was the PI. (Includes $100,000 in supplemental funding awarded in 1992.) Albert Einstein College of Medicine ($2,310,000 • 1998-1995). The grant supported a program to study the role of membrane receptors in the control of cell growth and differentiation. The primary targets of research were the molecular basis of cell proliferation and differentiation initiated by hormone-receptor interaction; mechanisms of determination of specific cell types in differentiating systems; and the regulation of biosynthesis, processing, and release of growth factors and hormones. Laboratories were established for a number of scholars; support was provided for graduate students, fellows, and visiting faculty; and new faculty were recruited. Richard Stanley was the PI. University of California, Berkeley ($8,500,0002 • 1989-1997). The grant provided funding for the Fund for Innovation, a new kind of intramural innovation grant for faculty. Funds provided support for 12 faculty members to investigate molecular structure using recombinant DNA technology or other sophisticated approaches to define basic biological processes such as the transport of proteins, enzymes, and other macromolecules through membranes. The grant was housed in the Department of Biochemistry. The award combined two applications into a multidisciplinary award that bridged biology and engineering in a study of the structure and function of receptors. Jeremy Thorner and Daniel Koshland were the PIs. Johns Hopkins University ($7,150,000 • 1989-1996). The grant provided funds to establish The Markey Center for Macromolecular Studies. The center, located within the School of Medicine, served as a focal point for research on structural biology of large molecules such as proteins and nucleic acids. The award enabled biophysicists, biochemists, molecular biologists, and computer experts to interrelate the structure and function of biological forms. In addition to salaries, the grant funded major equipment purchases and renovations. Jeremy Berg was the PI. Northwestern University ($5,890,0002 • 1989-1996). The grant created the Markey Program for Developmental Biology, an interdisciplinary pro- 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust gram that bridged the three campuses of the university, housed in the medical school. The grant provided funds for extensive equipment and construction costs as well as faculty salaries for 10 new physician-scientists. In addition, Markey funds created and supported the Northwestern University Transgenic Facility and provided space for the Northwestern University Biotechnology Facility. Harry Beaty was the PI and Philip Iannaccone was program director. (Includes $$390,000 in supplemental funds awarded in 1989.) Duke University ($8,00,0001 • 1990-1997). The grant supported the reorganization of medical sciences at the medical center including the development of three new basic medical sciences departments—Cell Biology, Genetics, and Neurobiology. Funds were used for faculty salaries, support of research laboratories, major equipment purchases, and programmatic support of the new departments. Ralph Snyderman was the PI. Thomas Jefferson University ($3,500,000 • 1990-1994). The grant supported the Jefferson Institute of Molecular Medicine. The grant covered the salaries of nine new tenured faculty; supported three core laboratories—a DNA repository, a DNA analysis laboratory, and a transgenic mouse laboratory; and supported the relocation of the institute into a new facility. Darwin Prockop was the PI. University of Virginia ($6,100,000 • 1990-1996). The grant supported a research institute to investigate the molecular mechanisms of cellular signaling processes. The new institute incorporated an existing institute of molecular biology and some activities of the Biodynamic Institute. About half of the grant was used for faculty salaries and half to set up and equip the research facility. Robert Carey was the PI. Temple University ($2,500,000 • 1990-1996). The grant supported the continued operation of the Fels Institute for Cancer Research and Molecular Biology. Funds covered partial support for 10 new junior faculty, supplies for these faculty, major equipment purchases, and support for postdocs and technicians. Research focused on molecular genetics, cell and developmental biology, immunology, and chemical carcinogenesis and molecular pharmacology. Carlo Croce was PI, followed by Premkumar Reddy. 1   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators addressing important problems in biomedical sciences awarded in FY 1996.

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Funding Biomedical Research Programs: Contributions of the Markey Trust University of Washington ($7,500,000 • 1990-1997). The grant funded the Lucille P. Markey Molecular Medicine Center, which built on programs developed at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center. Research was focused on gene therapy, developmental genetics and genetics of birth defects, and genetics of common disorders. Funding covered core facility costs including clinical, statistical, and laboratory staff; equipment; supplies; animals; and salary and start-up funds for new faculty. George Stamatoyannopolos was the PI. University of Colorado Health Sciences Center ($5,000,000 • 1991-1996). The grant provided support for the School of Medicine program in the molecular biology of cell proliferation. Markey funds supported programs that focused on interdisciplinary investigation of the molecular basis of cell proliferation, and the control of cell division by the Departments of Biochemistry, Biophysics and Genetics, Microbiology and Immunology, Pharmacology and Medicine. Funding supported renovation of a core facility, salary and start-up costs for new faculty, and graduate and postdoctoral training. Charles McHenry was the PI. New York University ($2,600,000 • 1990-1997). The grant provided salary and start-up support for four junior investigatorships to investigate the intersection of antigen processing and the control and signaling involved in the intracellular traffic of proteins. Two new faculty each from the Division of Immunology and the Department of Cell Biology collaborated in this study. Victor Nussenzweig was the PI. Cold Spring Harbor Laboratory ($4,500,0002 • 1991-1997). The grant provided support for the Neurosciences Center, dedicated to the study of the development and function of the nervous system, including processes of learning and memory, and how to attack diseases of the brain. Markey funding was commingled with funding from multiple foundations. Markey funding was dedicated to furnishing two floors of the center’s research laboratory, providing salary support, and purchase of major scientific equipment. James Watson was the PI. University of Vermont ($2,300,0002 • 1990-1998). The grant supported the development of the Markey Center in Molecular Genetics housed within the Department of Microbiology and Molecular Genetics. Funding 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust was equally divided for new faculty salary and start-up costs, major equipment purchases, and core facility operating costs. In addition, the award provided stipends for graduate students and postdoctoral fellows. Susan Wallace was the PI. Massachusetts Institute of Technology ($3,850,000 • 1991-1999). The grant provided support for research in neurobiology. Funding supported both pre- and postdoctoral fellows, renovation of a confocal microscopy facility, purchase of consumable supplies, and meetings and seminars. Additional funding was used to provide “seed money” for individual research projects by MIT faculty. Emilio Bizzi was the PI. Vanderbilt University ($5,000,0001 • 1991-1997). This grant supported a program that investigated molecular mechanisms of growth regulation, including the processes that lead directly to the uncontrolled growth of cancer cells. Although researchers from several departments contributed their expertise, the three departments at the core of the research were biochemistry, medicine, and cell biology. Funding supported three new faculty, training for young scientists, and competitive funding for promising pilot programs. Stanley Cohen was the PI. Memorial Sloan-Kettering Cancer Center ($2,700,000 • 1991-1994). The grant provided support for the cellular biochemistry and biophysics program. Research focused on (1) discovering the machinery that propagates and maintains the precise three-dimensional arrangement of organelles and biochemical processes in a cell, (2) determining the precise three-dimensional structure of this machinery using methods of X-ray crystallography and NMR spectroscopy, and (3) explaining these mechanisms of action in physical and chemical terms. Funding was used primarily for salary support for senior- and junior-level investigators and for equipment and supplies. Paul Marks was the PI. University of Rochester School of Medicine and Dentistry ($4,000,000 • 1991-1997). The grant provided support for research conducted in the Neurosciences Institute. The research focused on (1) neural regulation of the immune system response, (2) neural transplantation and regeneration, and (3) brain aging and Alzheimer’s disease. Funding provided sal- 1   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators addressing important problems in biomedical sciences awarded in FY 1996.

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Funding Biomedical Research Programs: Contributions of the Markey Trust ary support for senior researchers, recruitment and start-up costs for new faculty, a program of pilot projects to promising young investigators, construction and renovation of laboratories in the Department of Neurobiology and Anatomy, graduate student stipends, and the support of a primate colony. David Felten was the PI. University of Alabama at Birmingham ($1,500,000 • 1991-1995). The grant provided support for the interdisciplinary Neurobiology Research Center. The center’s mission was to determine the fundamental processes by which brain molecules and cells develop in newborns to facilitate perception, movement, learning, and memory. The award provided salary and start-up costs for new faculty, salary support for lab technicians and stipends for graduate students and postdoctoral fellows, and equipment purchases. Michael Friedlander was the PI. Fox Chase Cancer Center ($4,000,000 • 1991-1996). The grant provided support for the center’s Molecular Oncology Program. The research focus was a multidisciplinary investigation of genes involved in cancer and other factors that transform normal human cells into cancer cells. Scientists and physicians teamed to develop ways to reverse this process at the molecular level, including studies of gene therapy. Funding supported core scientists, primarily junior investigators, for salary support, equipment and supplies, and start-up costs and provided stipends for postdoctoral fellows and graduate students. Alfred Knudson was the PI. Florida State University ($4,500,0002 • 1991-2000). The grant provided funds to develop a program in structural biology through the Institute of Molecular Biophysics. The program was an interdisciplinary blend of the Departments of Biophysics, Biochemistry, and Molecular Biology and investigated basic biomedical problems through the study of actions of macromolecules, including study of their three-dimensional structure. Funding included start-up costs for new facility, construction and capital equipment costs, stipends for graduate students, and support for research associates and assistants. Lee Makowski was the PI. Harvard School of Public Health ($3,500,0002 • 1991-1998). The grant provided support to the Laboratory of Toxicology within the School of Public Health to investigate the effect of toxic substances—environmental 2   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators made in FY 1997.

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Funding Biomedical Research Programs: Contributions of the Markey Trust and otherwise—on various cells including bacterial and human cells. The grant funded salaries and start-up costs for new faculty, provided funding for competitive pilot projects, and supported an expanded training program for graduate students and postdocs. Armen Tashjian was the PI. Cornell University Medical College ($4,000,000 • 1992-1997). The grant provided funds to establish the Institute of Human Neuroscience housed in the Biomedical Research Center. Within the center, laboratories investigated pediatric neuroscience, neurophysiology vision, cellular neuroscience, Alzheimer’s research, multiple sclerosis research, and collaborative studies. Funding provided support and setup costs for the laboratories of several senior faculty, including salaries, stipends for graduate students and postdocs, and equipment and supplies. Fred Plum was the PI. The Burnham Institute (La Jolla Cancer Research Foundation) ($1,500,000 • 1992-1996). The grant supported research in cell recognition studies in the Biophysics Resource Center focused on solving three-dimensional structures of cell adhesion peptides and the synthesis of cell type-specific carbohydrates. The award provided the purchase and on-site installation of an NMR spectroscope. Erkki Ruoslahti was the PI. The Scripps Research Institute ($5,000,000 • 1992-1996). The grant supported the interdisciplinary application of genetics and molecular biology to advance understanding of the structure-function relationships of variously biologically important molecules. Research focused on the study of molecules responsible for cell-cell communication via chemical and electrical synapses, cell motility and cell division, regulation of the cell cycle, and transport from nucleus to cytoplasm. The award provided faculty salary, start-up support for new faculty, stipends for postdoctoral fellows and graduate students, and support for the purchase of major equipment. Norton Gilula was the PI. University of Illinois at Urbana-Champaign ($3,000,000 • 1992-1998). The grant provided funding at the Beckman Institute to establish a program in molecular biology of neural development and plasticity. Research focused on four key areas of developmental neurobiology: (1) the origins and character of the signals involved in neuronal cellular determination; (2) molecular-level migration of cells and neurons to their targets; (3) the recognition mechanism responsible for the precision of synaptic connections laid down during development; and (4) the molecular processes that give rise to alterations in the functional properties of nerve cells, particularly as related to plasticity, learning, and memory. Funding was used

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Funding Biomedical Research Programs: Contributions of the Markey Trust primarily for salary and start-up costs for new faculty, postdoctoral fellow and graduate student stipends, and major equipment. Theodore Brown was PI until 1992, replaced by Jiri Jonas. University of California, Santa Cruz ($2,500,000 • 1992-1999). The grant supported the development of the Center for Molecular Biology of RNA. A major function of the center was to encourage and support interaction among structural biologists, molecular geneticists, and biochemists and to promote understanding of how the structure of RNA influences its biological properties. Funding was used primarily for major equipment purchases, faculty start-up costs, and postdoctoral fellow stipends. Harry Noller was the PI. Cincinnati Children’s Hospital Medical Center ($3,500,000 • 1992-1996). The grant was used to develop the Center of Pediatric Molecular Genetics, at Children’s Hospital Medical Center and the University of Cincinnati. The center established five objectives: (1) to elucidate the molecular and pathogenesis of human inherited diseases and gene-influenced illnesses; (2) to develop new and improved methods for their detection; (3) to introduce and evaluate gene-based therapeutic strategies for the treatment of human diseases; (4) to provide the highest quality medical genetics care to affected families and patients; and (5) to educate and train physicians, geneticists, genetic counselors, and other allied health providers in the area of molecular and human genetics. Funding was used for faculty recruitment, salary, and start-up costs and for stipends for postdoctoral fellows and graduate students. Gregory Gabowski was the PI. Public Health Research Institute ($2,500,000 • 1992-1996). The grant supported research on the molecular basis of pathogenesis through the Molecular Pathology Program. The program focused on development of critical core support facilities and resources including Biosafety Level 3 (BL-3) containment labs for handling highly infectious materials, undated and advanced computing, light and flourescence microscopy, and routine DNA and protein imaging systems. Funding was used for seed grants to investigators, instrumentation, and recruitment of new faculty. Abraham Pinter was the PI. University of Wisconsin-Madison ($3,000,000 • 1992-2003). The grant supported research on the molecular basis of virus structure, replication, morphogenesis, host interaction, and pathogenicity in the Institute for Molecular Virology. A major focus of the grant was the development of a state-of-the-art molecular graphics laboratory. In addition to faculty sup-

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Funding Biomedical Research Programs: Contributions of the Markey Trust port, the grant provided start-up costs for new faculty and stipends for graduate students and postdoctoral fellows. The PI was Roland Rueckert. Princeton University ($4,500,000 • 1992-1997). The grant supported development of a program in structural cell biology within the Department of Biology. Research focused on exploring the relationship between the cell and its structure and assembly processes. Particular specialties of the program included cell biology, the cell membrane, the nucleus, and the transport of proteins in cells. Funding was used primarily for construction or renovation of shell laboratory space, the purchase of major equipment, start-up costs for new faculty, and stipends for graduate students and postgraduate fellows. Arnold Levine was the PI. Massachusetts General Hospital ($3,000,000 • 1993-1997). The grant provided five-year support for the development of physician-scientists in oncology at the Cancer Center modeled after the NIH physician-scientist program. The research focused on multidrug resistance genes and the development of strategies for their activation; genetic changes involved in metastasis, with emphasis on the metastasis suppressor gene (NM23); and the use of monoclonal antibodies, cytokines, and antisense oligonucleotides as antitumor agents. Funding provided salary and start-up costs for faculty, stipends for graduate students and postdoctoral fellows, and equipment purchases. Kurt Isselbacher was the PI. Mount Sinai Medical Center ($3,000,000 • 1993-1997). The grant provided support for a program in molecular biology, cell biology, and immunology. Research was targeted at three problem areas: (1) intricate patterns of nerve conductivity; (2) attempts to translate classical embryological concepts such as “induction” and “instructive interactions” into molecular terms; and (3) the relation of gene expression to spatial, positional, and temporal information in eukaryotic systems. Funds were for faculty salary and start-up costs and for graduate student stipends. The PI was Robert Lazzarini. University of Utah ($2,500,000 • 1993-1997). The grant provided funding to establish the Center for Protein Biophysics. The center’s research agenda investigated the structure, stability, and function of proteins. The center integrated the activities of structurally oriented scientists from the fields of biochemistry, biology, chemistry, and hematology-oncology. Funding was used primarily for the purchase of equipment for the center, salaries for technicians, and stipends for postdoctoral fellows and graduate students. Martin Rechsteiner was the PI.

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Funding Biomedical Research Programs: Contributions of the Markey Trust Joslin Diabetes Center ($3,500,000 • 1993-1999). The grant provided initial support for research on the molecular basis of cellular communication and metabolic regulation. Markey funding led to the development of five new programs: (1) signal transduction and cellular regulation, (2) vascular cell biology, (3) cellular growth factors, (4) tissue-specific regulation of gene expression, and (5) molecular immunology. In addition, the grant established two core laboratories to support these programs—one for molecular instrumentation and a core animal facility. Funds were used for faculty salary and start-up costs, construction, major equipment purchases, and support of the core laboratories. Ronald Kahn was the PI. Tufts University ($2,000,000 • 1993-1996). The grant provided support to the Departments of Physiology, Pathology, and Anatomy for research to determine the cellular targets of oncoproteins and growth factor receptors that mediate cell growth and transformation. Funds were directed primarily to support facilities needed for signal transduction research; to provide equipment and supply support for the Protein Chemistry, Baculovirus, and Molecular Biology Laboratories; and to support training of graduate students and postdoctoral fellows. Lewis Cantley was the PI. Salk Institute for Biological Studies ($2,600,0001 • 1994-1997). The grant provided support for a new Structural Biology Program. Funds were utilized for renovation of 5,000 square feet of space to accommodate the program and X-ray and computational equipment. Thomas Pollard was the PI. Baylor College of Medicine ($1,400,000 • 1995-1999). The grant provided support for organization of an enhanced research and training program in developmental and tumor biology. Markey funds enabled the initiation of a new Developmental Biology Program. Funding was used for faculty salary and start-up costs and for graduate student stipends. Bert O’Malley was the PI. University of Southern California ($1,800,000 • 1994-1998). The grant provided support for the University of Southern California Norris Institute for Genetic Medicine gene therapy program and founded the Lucille P. Markey Center for Gene Therapy. The goals of the center were to expand basic science strengths and develop new therapies in the molecular 1   Includes supplemental funds of $500,000 made in recognition of outstanding progress by Markey-supported investigators addressing important problems in biomedical sciences awarded in FY 1996.

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Funding Biomedical Research Programs: Contributions of the Markey Trust genetics of human disease, while providing new expertise in the areas of gene therapy and a research program to bridge the basic and clinical sciences. Funding was used for new faculty support. The PI was Larry Kedes. Dartmouth Hitchcock Medical Center ($1,500,000 • 1994-1997). The grant provided funding to support a life sciences curriculum, particularly for the development of a multidisciplinary genetics program. Research focused on the genetics of fundamental model systems, such as yeast and Drosophila; the genetics of vertebrate systems, such as mice and zebrafish; the genetics of heritable diseases, such as cancer and heart disease; and the development of transgenic models. Funding supported salary and start-up costs for new faculty positions. The PI was Andrew Wallace. Brown University School of Medicine ($1,300,000 • 1994-1998). The grant supported an interdisciplinary program to study the molecular and cell biology of disease. The grant funded new investigators, graduate and postgraduate training, opportunities for basic science training for medical students and residents, and equipment purchase. Agnes Kane and Arthur Landy were the PIs. Worcester Foundation for Biomedical Research. ($1,000,000 • 1994-1997). The grant provided four-year support for a multidisciplinary program of molecular and genetic approaches to cell motility within the Cell Biology Group. Research focused on discovering novel approaches to controlling neoplasis, metasis, and a variety of diseases of the nervous system by understanding how cells move, divide and establish, and change their shapes. Funding provided investigator support. Thoru Pederson was the PI. University of Colorado, Boulder ($1,500,000 • 1995-1997). The grant provided support to expand the Departments of Molecular, Cellular, and Developmental Biology and to create a Center for Mammalian Biology. The center focused on new research areas, particularly mammalian development, neurobiology, and other research relating to biology and health. Funding supported construction and renovation of the animal facility and salary and start-up costs for new faculty. Leslie Leinwand was the PI. Dana-Farber Cancer Institute $1,500,000 • 1995-1997). The grant provided for a new Division of Human Cancer Genetics. The goal of the new division was to identify human genes that, when damaged or lost, play key roles in transforming normal cells into cancer cells. Funds were used

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Funding Biomedical Research Programs: Contributions of the Markey Trust for faculty salaries and start-up costs, major equipment purchase, and support of the animal facility. David Nathan was the PI. University of Massachusetts Medical Center ($1,500,000 • 1995-1997). The grant provided three-year support to the Program in Molecular Medicine for collaborative basic and clinical research programs. Research focused on (1) immunology and signal transduction, with an emphasis on mechanisms of tolerance applicable to the pathogenesis of autoimmune insulin-dependent diabetes mellitus and its correction by islet transplantation, and (2) virology and gene expression related to HIV infection. Funding supported four new faculty and shared equipment. Michael Czech was the PI. University of Miami ($1,000,000 • 1995-1997). The grant provided four-year support for the study of neurotropic factors in spinal cord injury and repair. The research focused on tropic factors that have the capacity to influence neuronal health and regeneration in the spinal cord. Scott Whittemore was the PI. University of North Carolina, Chapel Hill ($1,500,000 • 1995-1997). The grant provided support for a Program of Molecular Therapy for Human Diseases within the Gene Therapy Center. Research focused on designing virus vectors for inserting copies of a healthy gene to replace mutated or absent genes, ensuring compliance of experimental forms of treatment with the safety and efficacy requirements of the Food and Drug Administration, and testing new therapeutics in human trials at the medical center. Faculty salaries, gene therapy equipment, and fellowships were supported. Oliver Smithies was the PI. University of Texas, Galveston ($1,000,000 • 1995-1996). The grant supported the Sealy Center’s established (NMR) spectroscopy program in structural biology. Research employed emerging technology to increase understanding of diverse macromolecular systems and to improve strategies for drug design. Funding was used for faculty and staff salaries for the NMR spectroscopy center. Samuel Wilson was the PI. Oregon Health Sciences University ($1,300,000 • 1995-1997). The grant provided support for studies of the genetic, cellular, and molecular basis of drug addiction conducted at the Vollum Institute. Research focused on investigation of the path from drug susceptibility behavior to the chromosomal location of a single “drug abuse gene” and to the electrophysiological and behavioral effects of mutating those genes in intact mice. Markey funds supported pilot projects and core facilities including: gene map-

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Funding Biomedical Research Programs: Contributions of the Markey Trust ping and behavioral genetics, gene targeting, neuronal imaging, and molecular pharmacology. Richard Goodman was the PI. Kennedy-Krieger Institute ($500,000 • 1995-1997). The grant provided support to determine the mechanisms by which central nervous system (CNS) capillaries develop and how they respond to injury for the purposes of defining how their growth and function might be regulated. The goal of the research was to demonstrate endothelial cell transplantation as a means of introducing genes for restoring normal CNS function. Funding provided faculty salaries, graduate student stipends, and equipment purchases. Gary Goldstein and John Laterra were the PIs. University of California, Davis ($1,600,000 • 1995-2002). The grant provided support for the establishment of the Center for Comparative Medicine, a collaborative effort of faculty from the Schools of Veterinary Medicine and Medicine and the California Regional Primate Research Center. Research investigated the pathogenesis of persistent viral infections and chronic viral diseases. There were three areas of emphasis: transgenics and the optimization of gene transfer methodologies, development and evaluation of anti-retrovirus drugs, and studies of biological responses to antiviral immune responses. Funding was used for faculty salaries, postdoctoral fellow stipends, and core support. Frederick Murphy was the PI. University of Florida ($1,600,000 • 1995-2000). The grant provided funding to establish the Markey Faculty Scholar Program in Neurobiological Research within the University of Florida Brain Institute. Funding supported five new faculty, designated as Markey Faculty Scholars, who facilitated new research collaborations with current basic and clinical University of Florida Brain Institute faculty and provided equipment for their research endeavors. William Luttge was the PI. University of Pittsburgh ($1,000,000 • 1995-1997). The grant provided support for studies seeking ways to alter genetic information to treat a variety of life threatening diseases. The long-term objectives of the research were to alter genetic information within cells or virus vectors to correct major metabolic and immunologic deficiencies, to introduce a self-renewing source of potent therapeutic factors or cells, or to block the auctions of deleterious genes or gene products. Funds were used to enhance core facilities, provide laboratory space for new faculty, and provide seed money for innovative pilot studies. Ronald Haberman was the PI.

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Funding Biomedical Research Programs: Contributions of the Markey Trust Harvard University ($1,600,000 • 1995-1998). The grant provided support to establish a combined Department of Biochemistry, Molecular Biology, and Developmental Biology. The research combined the conceptual and technical tools of genetics and cellular and molecular biology for approaching key problems of classical embryology—how different cell types arise during development and how those cells are arranged in tissues and organs. Funds provided a new vertebrate animal facility and provided seed money for pilot projects and collaborations. Jeremy Knowles was the PI. University of California, Irvine ($1,000,000 • 1995-1999). The grant provided 4-year support for the UCI-Markey Initiative in Human Neurobiology. The research focused on brain plasticity and specifically on the study of mechanisms for modulating neuropsychaiatric disorders. Markey funds were used to provide stipends for postdoctoral fellows and for initial support for young investigators. The Co-PIs were Ian Lipkin and Carl Cotman. Johns Hopkins University ($1,300,000 • 1995-1997). The grant provided 3-year support to develop a multidisciplinary research unit directed towards studies of the neural mechanisms in perception in the Zanvyl Krieger Mind/Brain Institute. The Markey award expanded the multidisciplinary activities in the areas of neuroanatomy, neurochemistry, experimental psychology, computational neurobiology, and cognitive neuroscience. Funds supported faculty investigators. The Co-PIs included Guy McKhann and Kenneth Johnson. Georgetown University ($1,000,000 • 1995-1997). The grant provided support for the Center for Molecular and Human Genetics to promote research and training on the role of genetic elements in normal development and their altered role in the pathology of cardiac, cancer, developmental, and neurodegenerative disorders. Markey funds supported new faculty, laboratory equipment, and graduate training. John Griffith was the PI. Cornell University ($1,200,000 • 1995-1999). The grant provided support for a program to provide rapid structural analysis of drug targets and their complexes with potential drug molecules utilizing fast charge-coupled device-based x-ray detectors. Additional research focused on the development of more powerful computer algorithms for the analysis of target macromolecules and computer-aided design of potential drug molecules. Funds were used for core personnel salaries and graduate training. The PI was Steven Ealick.

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Funding Biomedical Research Programs: Contributions of the Markey Trust Children’s Memorial Medical Center ($1,000,000 • 1995-1997). The grant provided 3-year support for a research program in human and molecular genetics in the Children’s Memorial Institute for Education and Research (CIMER). Markey funds also facilitated a link with Northwestern University Medical School. The research focused on establishing a molecular biology and cytogenetics laboratory and established a postdoctoral training program. In addition to strengthening the equipment base at the Institute, the grant provided postdoctoral support in research genetics. Martin Myers was the PI. Rice University ($1,200,000 • 1995-1997). The grant provided state-of-the-art instrumentation to enhance program development at the Institute of Biosciences and Bioengineering and the Keck Center for Computational Biology. The new equipment facilitated interdisciplinary collaboration in a series of projects involving: protein structure, design and determination of cellular function; atherosclerosis, cholesterol metabolism, thrombosis, and hemodynamics; tissue reconstruction by cell transplantation with biodegradable polymers; biotechnology; and neurobiology. Kathleen Matthews was the PI. Rush-Presbyterian-St. Luke’s Medical Center ($1,000,000 • 1995-1998). The grant supported studies on the cell and molecular biology of hemopoiesis in vitro. Research investigated processes that control and organize cell proliferation and differentiation, processes underlying such disparate phenomena as embryogenesis and maintenance of adult multicellular organisms in a health state. The investigators modified the stromal and the primitive progenitor cells so that cell production in vitro mimicked that which occurred in vivo. Harvey Preisler and Azra Raza were the Co-PIs. Schepens Eye Research Institute ($1,000,000 • 1995-1997). The focus of this program was ocular immune privilege, the controlled expression of immunity and inflammation in the eye. The goal of the grant was to identify the unique molecular mechanisms by which the eye creates and sustains a local microenvironment that suppresses immunologic inflammation, and explains the phenomena of immune privilege. Funds provided salary support for a primary investigator, technicians, and the purchase of major equipment. J. Wayne Streilein was the PI. Stanford University ($1,200,000 • 1995-1997). The grant supported interdisciplinary study of the ability of cells to turn on or turn off subsets of genes in precise temporal/spatial order in response to ever changing environmental challenges. The program focused on regulation at the mo-

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Funding Biomedical Research Programs: Contributions of the Markey Trust lecular level of gene expression in the control of cellular and organismal development and cellular physiology. The grant provided funds for graduate stipends and postdoctoral fellows and for the purchase of major equipment. Patricia Jones was the PI. State University of New York, Buffalo ($1,000,000 • 1995-1997). The grant supported a program in microbial pathogenesis. This program was a collaboration of 24 scientists with diverse research interests and numerous shared projects in molecular parasitology, sexually-transmitted diseases, vaccine development for pediatric infectious diseases, the molecular biology of tropical diseases, toxoplasmosis, and leishmaniasis. The funds provided salary and start-up costs for new faculty. John Hay, Philip LoVerde, and Bruce Hoims were the Co-PIs. Texas A & M University ($1,000,000 • 1995-1998). The grant supported development of a program in structural analysis of cell signaling molecules within the Albert B. Alkek Institute of Biosciences and Technology in Houston. The program’s mission focused on the study of molecular mechanisms of the cell signaling processes and the understanding of structural changes in the production of hormones, growth factors, cytokines, and cell behavior. Funds supported new faculty and the purchase of major equipment. Fuller Brazer and O. D. Butler were the Co-PIs. University of Texas - Houston Health Science Center ($1,000,000 • 1995-1997). Funds supported the Center for the Neurobiology of Learning and Memory. The Center served as a unifying locus for the physiological study of learning and memory from one of four perspectives: (1) molecular mechanisms, (2) cellular integration, (3) modifications of neuronal structure, and (4) real-time neural network simulations. Funds supported major equipment purchases for the Center and start-up costs for new faculty. John Byrne was the PI. University of Maryland Biotechnology Institute ($1,000,000 • 1995-1997). The grant provided 3-year support for studies of bioactive compounds for marine organisms living in extreme environments. The focus of the research was to determine the biochemical basis for their biological activity in order to facilitate drug design through molecular modeling and to enable their production through organic synthesis or expression in prokaryotic or eukaryotic cell culture systems. Funds supported core operational expenses, equipment, and graduate stipends. Rita Colwell was the PI.

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Funding Biomedical Research Programs: Contributions of the Markey Trust University of Kentucky ($1,900,000 • 1995-1998). The grant provided 4-year support for immunotherapy and gene therapy programs at the Lucille P. Markey Cancer Center. Specific goals included (1) building expertise on the role of T-cells in the idiotypic network as a basis for critical investigation of anti-idiotype vaccines and (2) advancing gene cancer therapy by increasing tumor specificity in gene delivery through new techniques in the selective targeting of tumor cells. Funds provided faculty salary and start-up costs. Kenneth Foon was the PI.