Biographies: Michael Weiss, MD, PhD

Michael Weiss, MD, PhD
Professor and Chairman of Biochemistry Department
Case Western Reserve University

In 1985, Weiss earned his M.D. degree, summa cum laude, from the Harvard Medical School, and, in 1986, the Ph.D. degree in biophysics from Harvard University. He then completed a residency in internal medicine and a fellowship in medicine at Brigham and Women's Hospital, Boston, from 1985 to 1988. He is board certified in internal medicine.
He has received numerous honors and awards, including the Fletcher Scholars Awarrd in Cancer Research and the Harvard Medical School Soma Weiss Research Award. In 1994, he was named a Lucille Markey Scholar and Bane Scholar at the University of Chicago and Established Investigator of the American Heart Association. He was also appointed to the White House Comission en Presidential Scholars.

Research in the Weiss laboratory focuses on two areas: control of gene expression, and protein folding and misfolding. Links are made to clinical phenotypes or disease mechanisms. Studies of gene expression include analysis of mammalian and viral transcription factors.

1. Protein-nucleic acid interactions; structural aspects of gene regulation. Application to the birth defects, regulation of metabolism and nuclear oncoproteins.
2. Peptide hormones; principles of receptor recognition; insulin and diabetes mellitus; structure-activity relationships and protein design. Post-receptor protein-phosphoprotein interactions and relation to malignant transformation. Application to cytoplasmic oncoproteins.
3. Prokaryotic Transcriptional Regulation and Lambdoid Phages with application to pathogenesis and infectious disease.

Mutations or deletions in human transcription factors can, for example, deregulate organogenesis and cause genetic susceptibility to malignancy. A model is provided by transcriptional factors regulating testicular differentiation. Gonadal dysgenesis and gonadoblastoma are associated with mutations or deletions in the Y chromosome (interval 1A1) or chromosome 9 (interval 9p24), mapped to genes SRY or DMTR1/DMTR2, respectively. Biochemical and structural studies of the DNA-binding motifs encoded by the loci are in progress.

Studies of protein folding and misfolding focus on insulin and diabetes-related transcription factors in the pancreatic beta cell. Mutations in the latter are associated with impaired glucose-stimulated insulin secretion leading to maturity-onset diabetes of the young. Structural studies focus on a novel four-helix bundle in hepatic nuclear factor 1a.