May 12, 2000

HHMI funds enhance genetics research efforts

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HHMI funds enhance genetics research efforts

A recruiting effort bolstered by funds from the Howard Hughes Medical Institute Resources Program for Medical Schools has added six new faculty members to expand genetics research at Vanderbilt University Medical Center.

The HHMI grant, awarded in 1995, was focused on developing genetics here and included funds to hire six junior faculty, start core facilities, and enhance the operation of other resources relevant to genetic research.

"A highlight of the program was selecting six new investigators," said Dr. Alfred L. George Jr., Grant W. Liddle Professor of Medicine, director of the division of Genetic Medicine, and co-chair of a committee that recruited four of the new faculty members. "This terrific group of young researchers has already enriched the depth and breadth of genetic talent at Vanderbilt."

"I do not believe that we would have gotten the quality of people that we did, without the additional funds provided by the HHMI grant," George added. "The marketplace right now is highly competitive and is supporting larger startup packages and higher salaries for new investigators. For Vanderbilt to continue getting this quality faculty, we have to make serious investments."

A committee chaired by Brigid L. M. Hogan, Ph.D., Hortense B. Ingram Professor of Molecular Oncology, and Dr. Mark A. Magnuson, assistant vice chancellor for Research, recruited the first two HHMI Research Scholars. George and Magnuson chaired the committee that completed the recruitment.

"The group represents a wide array of research expertise," George said. "Two of the investigators are focused on human genetics, three utilize advanced mammalian — primarily mouse — model systems, and one uses proteomics, an area that is completely new to Vanderbilt."

HHMI Research Scholars are:

Chin Chiang, Ph.D., assistant professor of Cell Biology.

Chiang received his Ph.D. in Genetics and Cell Biology from Washington State University. He carried out postdoctoral research at Johns Hopkins University with Dr. Philip A. Beachy and was a research associate at the National Institute of Child Health and Human Development in the laboratory of Dr. Heiner Westphal before coming to Vanderbilt in 1997.

Chiang's research focuses on the molecular mechanisms that control mammalian development, especially intricate processes like the generation of nerve cells in the spinal cord, the development of the digestive and respiratory systems from a simple sheet of cells, and the formation of fingers and toes. His group studies a signaling molecule important to the development of many organ systems called "Sonic hedgehog." Defective Sonic hedgehog signaling in human beings causes clinical disorders including the birth defect holoprosencephaly and various forms of cancer.

Dr. Christopher D. Ferris, Ph.D.

Ferris, who will join the faculty in July, received his M.D. and Ph.D. degrees from the Johns Hopkins University School of Medicine. He remained at Johns Hopkins to complete his residency and fellowship training in Internal Medicine and Gastroenterology, recently serving as a senior clinical and research fellow working with Dr. Solomon H. Snyder.

Ferris' research focuses on signaling in the liver and enteric nervous system — the branch of the peripheral nervous system that controls the gut. He is especially interested in understanding the roles of nitric oxide and carbon monoxide as neurotransmitters in the enteric nervous system. His recent findings linking nitric oxide deficiency to diabetic gastropathy suggest new therapeutic possibilities for this complication of diabetes.

Ferris also is studying iron homeostasis and has discovered that an enzyme called heme oxygenase-1 determines cellular iron levels and protects cells from stress-induced cell death. Disruption of iron homeostasis may contribute to human diseases including hemochromatosis, hepatitis C infection, and alcoholic liver disease.

Andrew J. Link, Ph.D., Ingram Assistant Professor of Cancer Research and assistant professor of Microbiology and Immunology.

Link received his Ph.D. in Genetics from Harvard University and then completed postdoctoral research at the University of Washington with Dr. John R. Yates, III. He was a staff scientist at Millennium Predictive Medicine, Inc. in Cambridge, Massachusetts before joining the Vanderbilt faculty in 1999.

Link uses proteomic methods for deciphering biological processes in the cell. He recently developed a process termed Direct Analysis of Large Protein Complexes (DALPC), which couples multidimensional chromatography to mass spectrometry in order to identify the components of multi-protein complexes. Link is studying the protein complexes that modulate activities like DNA replication, protein translation, and protein secretion, using the model organisms yeast and bacteria.

Dr. Jeffrey R. Smith, Ph.D., Ingram Assistant Professor of Cancer Research and assistant professor of Medicine.

Smith received his M.D. and Ph.D. degrees from the University of Texas Southwestern Medical Center, where his dissertation research mentors were Nobel laureates Drs. Michael S. Brown and Joseph L. Goldstein. He completed residency training in Internal Medicine at the University of Michigan and then joined the laboratory of Dr. Francis S. Collins at the National Human Genome Research Institute. While at the NHGRI as a senior staff fellow, Smith completed the Clinical Investigator Pathway of the American Board of Internal Medicine. He came to Vanderbilt in 1999.

At the NHGRI, Smith developed a high-throughput genotyping facility that successfully identified regions of chromosomes 1 and X that predispose patients to hereditary prostate cancer. He is developing a similar high-throughput genomics laboratory at Vanderbilt that will pursue cancer-causing genes in patients cared for at the Vanderbilt-Ingram Cancer Center. A significant aspect of the work involves developing the technology (software and hardware tools) to collect and analyze the volumes of data required in the genetic mapping of complex traits such as prostate cancer.

Michelle Southard-Smith, Ph.D., assistant professor of Medicine and Cell Biology.

Southard-Smith completed her Ph.D. in Genetics and Development at the University of Texas Southwestern Medical Center. She carried out postdoctoral research at the University of Michigan Medical Center with David T. Burke, Ph.D. and at the National Human Genome Research Institute with William J. Pavan, Ph.D. Southard-Smith joined the Vanderbilt faculty in 1999.

Southard-Smith is utilizing molecular genetic approaches to investigate the development of the enteric nervous system, the branch of the peripheral nervous system that controls gut motility. Abnormalities in enteric nervous system development give rise to gastrointestinal disorders like Hirschsprung disease and neuronal intestinal dysplasia, and may also contribute to the pathogenesis of irritable bowel syndrome and chronic intestinal pseudo-obstruction. Southard-Smith's research uses mouse models including the "dominant megacolon" mouse, a model of Hirschsprung disease, to identify and characterize genes involved in enteric nervous system development.

James S. Sutcliffe, Ph.D., assistant professor of Molecular Physiology and Biophysics.

Sutcliffe received his Ph.D. in Biochemistry and Genetics from Emory University and then completed postdoctoral research training at Baylor College of Medicine in Houston with Dr. Arthur L. Beaudet. He joined the Vanderbilt faculty in 1997.

Sutcliffe is interested in understanding the genetic causes of susceptibility for autism, as well as the molecular genetics and gene-phenotype relationships for Prader-Willi syndrome and Angelman syndrome.

The three disorders share one common theme in that all have been shown to involve defects in a common region on human chromosome 15. Sutcliffe's research is focused on identifying and characterizing the genes involved in these disorders and understanding how the genes may be regulated by genomic imprinting, a mechanism that restricts a gene's expression to one of the two chromosomes we inherit from our parents.