Jason D. Weber, Ph.D.

Internal Medicine
Molecular Oncology
Cell Biology and Physiology

Cancer Biology Program
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

  • Breast cancer, translation, RNA editing, tumor suppressors, oncogenes

  • 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:

Cottrell K.A., Chiou R.C. and Weber J.D. (2020). ARF suppresses 5’-terminal oligopyrimidine mRNA translation. Scientific Reports, i10:22276-89.

Kung C.P., Cottrell K.A., Ryu S., Bramel E.R., Kladney R.D., Bross E.A., Maggi L.B. and Weber J.D. (2020). Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer. Oncogene, 40:189-202.

Dania V., Liu Y., Ademuyiwa F., Weber J.D., and Colditz G.A. (2019). Associations of race and ethnicity with risk of developing invasive breast cancer after lobular carcinoma in situ. Breast Cancer Research, 21:120-6.

Liu Y., West R., Weber J.D., and Colditz G.A. (2019). Race and risk of subsequent aggressive breast cancer following ductal carcinoma in situ. Cancer, 125:3225-3233.

Wang J. Yuan Z., Weber J.D., and Zhang Y. (2019). DHX33 interacts with AP-2b to regulate gene expression and promote cancer cell survival. Molecular and Cellular Biology, 39:1-20

Last Updated: 7/2/2020 2:07:54 PM

Back To Top

Follow us: