Jason D. Weber, Ph.D.
- Associate Professor
- Department of Medicine
- Oncology Division
- Molecular Oncology Section
- Oncology Division
- Department of Cell Biology & Physiology
- Department of Medicine
- Research interests
- Cell cycle
- Tumor suppressors
- Oncogenes
Research
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 Ras 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 is not be strictly linear, opening the door for further research into other ARF functions within the nucleolus.
The uniqueness of ARF resides in its nucleolar localization, a property that underlies its most basic tumor suppressive function. My lab is using biochemical and proteomic techniques to identify all protein components of the nucleolus in order to study the nucleolar dynamics of ARF tumor suppression. Related to this goal, we have identified several nucleolar oncoproteins involved in various aspects of ribosome biogenesis. Many of these proteins are overexpressed or amplified in human breast cancers, suggesting that defects in ribsome biogenesis might themselves prove oncogenic.
Our goal is to understand the basic mechanisms behind ARF's tumor suppressive capabilities and to relate these processes to our growing knowledge of human cancer progression. Additionally, ARF appears to antagonize ribosome processing as well as the nucleocytoplasmic shuttling of maturing ribosomal components. Numerous projects in the lab are aimed at understanding this basic process and how it might impact tumor growth and progression. Members of the lab are translating their findings into clinical settings and potential application through numerous collaborations with Medicine faculty.
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The ARF-regulated checkpoint connects the RB and p53 pathways
From: Sherr CJ, Weber JD
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Biographical Sketch
Education
| 1993 | BS (Biotechnology), Bradley University, Peoria, IL |
| 1997 | PhD (Cell & Molecular Biology), Saint Louis University, St. Louis, MO |
Professional Experience
| 1993-1994 | Scientist, Immunoinflammatory Diseases Research Group, Monsanto/G.D. Searle, St. Louis, MO (laboratory of Peter C. Isakson) |
| 1997-2001 | Associate, Howard Hughes Medical Institute, Tumor Cell Biology Lab, 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 |
University Committees
| 2001-present | Cellular Proliferation Program, Siteman Cancer Center |
| 2002-present | Neuro-Oncology Research Group, Founding Member |
| 2004-present | Division of Biological and Biomedical Sciences Admissions Committee |
| 2005-present | Siteman Cancer Center Urology Research Group |
| 2006-present | Division of Biological and Biomedical Sciences, Molecular Cellular Biology Steering Committee |
| 2006-2009 | Molecular & Cellular Biology Graduate Program, Director for Recruiting |
| 2006-present | Division of Biological and Biomedical Sciences Admissions Committee, Co-Chair |
| 2006-present | Breast Cancer Research Group, Founding Member |
| 2006-present | ACS-IRG Committee, Washington University |
| 2009-present | Co-Director, Molecular & Cellular Biology Graduate Program, Washington University |
National Committees
| 2002-2005 | American Heart Association, Cell Transport Study Section |
| 2005-2008 | Department of Defense, Army, SBIR Proteomics and Neoplasia Committees |
| 2006 | National Institutes of Health, Cell Signaling and Dynamics Study Section, Ad Hoc Member |
| 2007 | National Institutes of Health, MONC Study Section, Ad Hoc Member |
| 2007 | Cancer Research UK Investigator Grants, Ad Hoc International Member |
| 2008-2009 | National Institutes of Health, ZRG Special Emphasis Panel, Ad Hoc Member |
| 2009 | American Association for Cancer Research Annual National Meeting, Organizer and Reviewer for Cell Growth Pathways |
Honors & Awards
| 1993 | Monsanto/G.D. Searle Competitive Summer Internship |
| 1993 | Bradley University Outstanding Research Award |
| 2001 | Edward Mallinckrodt, Jr. Foundation Scholar |
| 2002 | Pew Scholar in Biomedical Sciences |
| 2005, 2006, 2007, 2008 | Distinguished Service Teaching Award, Washington University |
| 2007 | Teacher of the Month, Medical Student Class of 2009 |
| 2008 | CDMRP, Era of Hope Scholar in Breast Cancer Research |
| 2008 | American Cancer Society Scholar |
Professional Societies
| American Society for Microbiology |
- Updated: June 5, 2009
