WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

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Multiple genetic steps that result in the deregulation of two tumor suppressor pathways, governed by the p53 and retinoblastoma (Rb) tumor suppressors, pave the road to cancer in humans. The p53 and Rb proteins require communication between upstream effectors and activators in order to sense when a cell is under stress. Two proteins encoded by the INK4a/ARF locus, p16INK4a and p19ARF, functionally target the Rb and p53 tumor suppressors, respectively. These four proteins are among the most frequently affected genes in human cancer. We are interested in understanding the individual contribution of these proteins to the development of human cancers and how they may be regulated by upstream signals.

We have previously shown that ARF is induced by inappropriate mitogenic signals, such as those emanating from the Myc and adenovirus E1A oncoproteins, and it diverts hyperproliferating cells to undergo p53-dependent cell cycle arrest or apoptosis. This is accomplished through ARF's interaction and nucleolar sequestration of the p53-negative regulator Mdm2. However, mounting evidence from our lab suggests that the ARF-p53-Mdm2 pathway may not be strictly linear. While p53-null mouse embryo fibroblasts are resistant to ARF overexpression, cells deficient for Mdm2 and p53 are sensitive to ARF-induced growth arrest indicating that ARF can act as a bona fide tumor suppressor independent of p53 and that Mdm2 can antagonize this effect, although a defined mechanism is lacking. The immediate goal of my lab is to identify and characterize this alternative pathway and its role in suppressing tumor formation.

The ARF-regulated checkpoint connects the RB and p53 pathways From: Sherr CJ, Weber JD The ARF/p53 pathway. Curr Opin Genet Dev 2000 Feb;10(1):94-9

Education

1993	BS (Biotechnology), Bradley University, Peoria, IL
1997	PhD (Cell & Molecular Biology), Saint Louis University, St. Louis, MO

Professional Experience

1993-1994	Research Fellow, Immunoinflammatory Diseases, Monsanto/G.D. Searle, St. Louis, MO (laboratory of Peter C. Isakson)
1997-2001	Postdoctoral Fellow, Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN (laboratory of Charles J. Sherr)
2001-2007	Assistant Professor, Departments of Internal Medicine and Cell Biology & Physiology, Washington University, St. Louis, MO
2007-present	Associate Professor, Departments of Internal Medicine and Cell Biology & Physiology, Washington University, St. Louis, MO

Honors

1993	Monsanto Internship
2001-2004	Edward Mallinckrodt, Jr. Foundation Scholar
2002-2006	Pew Scholar in Biomedical Sciences
2005, 2006, 2007	Distinguished Service Teaching Award
2006	Medical School Teacher of the Month
2008-2013	Era of Hope Scholar in Breast Cancer

University Committees

2004-present	Division of Biology and Biomedical Sciences Admissions Committee, Chair Committee B
2006-present	Division of Biology and Biomedical Sciences, Molecular Cell Biology Steering Committee
2006-present	Division of Biology and Biomedical Sciences, Assistant Director for Recruiting
2006-present	Breast Cancer SPORE Group, Founding Member

National Committees

2002-2005	American Heart Association, Cell Transport Study Section
2005-present	Department of Defense, Army, SBIR Proteomics and Neoplasia Committees
2006	National Institutes of Health, Cell Signaling and Dynamics Study Section, Ad Hoc Member
2006-2007	Cancer Research UK Investigator Grants, Ad Hoc International Member
2007-present	National Institutes of Health, Molecular Oncogenesis Study Section, Ad Hoc Member

Professional Societies

American Society for Microbiology

Updated: April 16, 2008