Trey Westbrook, Ph.D.

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Trey Westbrook, Ph.D.

Robert C. Welch Chair in Chemistry

Phone

713-798-5364

Email

thomasw@bcm.edu

Positions

Robert C. Welch Chair in Chemistry: Baylor College of Medicine

Professor: Molecular and Human Genetics
Baylor College of Medicine

Professor: Biochemistry & Molecular Biology
Baylor College of Medicine

Faculty Member: Graduate Program in Genetics and Genomics
Baylor College of Medicine

Faculty Member: Graduate Program in Cancer & Cell Biology
Baylor College of Medicine

Director, Cell-Based Assay Screening Shared Resource: Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States

Emeritus McNair Scholar: Baylor College of Medicine
Houston, Texas United States

Addresses

BCM-MD Anderson Hall (Office)
: Room: BCMA-304BE
Houston, TX 77030
United States

Education

BS from Allegheny College: 01/1997 - Meadville, Pennsylvania United States

PhD from University of Rochester School of Medicine and Dentistry: 01/2003 - Rochester, NY United States

Post-Doctoral Fellowship at Harvard Medical School: 01/2007 - Boston, Massachusetts United States

Professional Interests

Mechanisms and models of breast cancer
Cancer genetics and therapeutic discovery

Professional Statement

Cancers are driven by genomic and epigenetic alterations that result in the activation of cellular proto-oncogenes and the inactivation of tumor suppressor genes. Although high-throughput genomic approaches have begun to establish extensive catalogs of gene alterations in human tumors, the genes that control tumor genesis, progression, and response to therapies are often concealed by the complex chromosomal instability in cancer cell genomes. This challenge is exacerbated by the lack of functional annotation for the vast majority of genes in the human genome. Thus, functional approaches are critical for identifying the genetic programs underlying cancer pathogenesis. Our laboratory applies genome-wide RNA interference (RNAi) and other technologies to the unbiased discovery of cancer genes and networks. Specifically, we focus on two areas of cancer gene discovery: Discovering new oncogene-induced “stress pathways” and translating these pathways into cancer therapies

The cancer community has largely studied the effects of oncogenes and tumor suppressors and how they contribute to the “pro-tumorigenic” hallmarks of cancer cells. However, it has also become clear that oncogenes themselves induce a variety of stresses in cancer cells such as metabolic reprogramming, oxidative pressures, mitotic instability, and proteomic imbalance. These stress phenotypes, sometimes collectively referred to as oncogenic stress, can serve to antagonize tumor growth and survival. The idea that oncogenes confer a highly stressed state onto cancer cells predicts that strategies to exacerbate one or more of these oncogene-induced stresses may tilt this balance in favor of killing cancer cells. We have been interested in exploiting the idea of oncogene-induced stresses for therapeutic discovery by tackling 3 poorly understood questions: (1) what are the molecular mechanisms by which prominent oncogenes (ex. Myc, Ras, etc.) induce these stresses? (2) how do cancer cells tolerate these stresses? and (3) are these stress support pathways different in normal and tumor cells? By using forward genetic approaches, we have made surprising discoveries about the endogenous cell pathways that are required to tolerate predominant oncogenic drivers like c-Myc (ex. Kessler et al., Science 2012). We are now extending these studies by elucidating the stress support pathways that enable cancer cells to tolerate other prominent drivers. Identifying new oncogene / tumor suppressor networks via functional genetic screens

With the explosion of genomic data emerging from TCGA, COSMIC, and other annotations of cancer genomes, there are fundamental challenges in (1) discerning which mutant genes are critical cancer drivers, (2) how these drivers are connected in genetic / signaling networks, and (3) how these cancer gene networks can be exploited for new therapies. We are addressing these important questions by developing genetic screens in human and mouse systems for new cancer gene networks. By combining new genetic technologies and engineered cell systems, we are uncovering new tumor suppressors (PTPN12, REST, INPP4B, etc.) and oncogenes (PLK1, TEX14, etc.) that control tumor initiation and progression (ex. Westbrook et al., Nature 2008; Sun et al., Cell 2011; Pavlova et al., eLife 2013). Through orthogonal studies, we have assembled these cancer genes into interconnected networks and uncovered new entrypoints for cancer therapies. For example, our group discovered a new tumor suppressor network that is disrupted in more than 70% of aggressive triple-negative breast cancers (TNBCs), with the tyrosine phosphatase PTPN12 acting as a core component of this network. Importantly, disruption of this tumor suppressor network leads to the concerted hyper-activation of a class of receptor tyrosine kinases. These kinases work together to drive TNBC and probably other cancers. Importantly, we have shown that pharmacologic inhibition of these collaborating kinases leads to tumor regression of primary TNBCs in vivo. We are currently dissecting the mechanism(s) by which these signaling pathways cooperate, and translating these discoveries into new clinical trials for TNBC patients at Baylor.