Jason D. Weber, Ph.D.

Associate Professor
Internal Medicine
Molecular Oncology
Cell Biology and Physiology

Molecular Cell Biology Program
Molecular Genetics and Genomics Program

  • 314-747-3896

  • 314-747-3898

  • 314-747-2797

  • 8069

  • ICCE Institute, BJC-IH Building, 7th Floor, Room 7609

  • JWEBER@wustl.edu

  • http://www.icce-wustl.org/jason-weber-lab.html

  • cancer, cell cycle, translation, RNA metabolism, cell signaling, tumor biology, tumor suppressor

  • Role of tumor suppressors and oncogenes in growth control

Research Abstract:

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 how cells regulate their growth rates and to relate these processes to our growing knowledge of human cancer progression. Numerous projects in the lab are aimed at understanding these processes and how they might impact tumorigenesis. Members of the lab are translating their findings into clinical settings and potential application through numerous collaborations with School of Medicine physicians.

Selected Publications:

Zhang Y., You J., Wang X., and Weber J.D. (2015). The DHX33 RNA helicase promotes mRNA translation initiation. Molecular and Cellular Biology, 35:2918-31.

Zhang Y., Baysac K.C., Yee L.F., Saporita A.J., and Weber J.D. (2014). Elevated DDX21 regulates c-Jun activity and rRNA processing in human breast cancers. Breast Cancer Research, 16:449-467.

Forys J.T., Kuzmicki C.E., Saporita A.J., Winkeler C.L., Maggi L.B., and Weber J.D. (2014). Arf and p53 coordinate tumor suppression of an oncogenic IFN-β-STAT1-ISG15 signaling axis. Cell Reports, 7:514-26.

Kuchenruether M.J. and Weber J.D. (2014). The ARF tumor suppressor controls Drosha translation to prevent Ras-driven transformation. Oncogene, 33: 300-307.

Zhang Y., Saporita A.J., and Weber J.D. (2013). P19ARF and RasV12 offer opposing regulation of DHX33 translation to dictate tumor cell fate. Molecular and Cellular Biology, 33: 1594-607.

Miceli A.P., Saporita A.J., and Weber J.D. (2012). Hyper-growth mTORC1 signals translationally activate the ARF tumor suppressor checkpoint. Molecular and Cellular Biology, 32: 348-64.

Last Updated: 9/6/2016 9:27:28 AM

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