Next-generation techniques for analyzing cancer genetics are revealing networks of interdependent genes that may allow researchers to find new vulnerabilities. Researchers hope to identify more possible drug targets to shut cancer down or keep it from metastasizing.
To analyze the complex biological data, bioinformaticist Traver Hart was recruited in 2016 from the University of Toronto, where he was a postdoctoral researcher, to The University of Texas MD Anderson Cancer Center. With the help of a First-Time Tenure-Track Award from CPRIT, Hart returns to his home state, having grown up and studied in Texas.
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Next-generation techniques for analyzing cancer genetics are revealing networks of interdependent genes that may allow researchers to find new vulnerabilities. Researchers hope to identify more possible drug targets to shut cancer down or keep it from metastasizing.
To analyze the complex biological data, bioinformaticist Traver Hart was recruited in 2016 from the University of Toronto, where he was a postdoctoral researcher, to The University of Texas MD Anderson Cancer Center. With the help of a First-Time Tenure-Track Award from CPRIT, Hart returns to his home state, having grown up and studied in Texas.
Hart tries to find genes that are essential for keeping cancer cells alive, but that aren’t essential in normal cells. Based on how they are related to other genes, he also tries to infer the function of specific genes and the proteins they code for. This specialty, called “functional genomics,” may help researchers identify the functions of many genes whose ultimate cellular roles are still unknown.
“Of the 20,000 or so protein-coding genes in the human genome,” Hart says, “we have a pretty good idea of what 1/3 to 1/2 of them do, and the rest is largely a mystery.”
His goals are twofold: to predict what chemotherapies might be beneficial for specific cancer types, and to identify new potential therapeutic targets that could be exploited to kill cancer. He’s focusing initially on colorectal cancer by participating in MD Anderson’s Colorectal Cancer Moon Shot ™ and collaborating with researchers working on prostate cancer. However, his techniques are readily expanded to many different cancer types. In fact, much of the computational technology and experimental tools he’s already developed are being disseminated to other labs throughout MD Anderson.
Much of his work is based on CRISPR-based gene knockout screens of cancer cells. “If you knock out a gene in a particular cancer cell and it kills that cell, and you knock out that same gene in a normal cell and it doesn’t kill that cell,” Hart says, “then maybe you’ve identified a potential therapeutic target.”
Hart’s efforts extend beyond computation. In the laboratory, he is improving CRISPR screening technology: making it more efficient, able to work on a smaller scale, and able to target more than one gene at a time. Normally, screens to identify which genes are essential operate on the scale of tens of millions of cells, which require propagation over many weeks in a controlled environment. Hart’s ultimate goal is to make the technology work on the scale of a single cell, which would enable him to identify essential genes using in vivo models that better mimic a patient’s tumor.
He hopes his research will be able to inform clinicians about which combinations of therapies are likely to be most beneficial for which type of cancer patient, and also enable physicians to stay one step ahead of cancer’s ability to evolve resistance to therapy.
Hart says most of his research wouldn’t have been possible without CPRIT support. “This is a large-scale, complicated experimental and computational enterprise,” he says, “and I would say that none of the technology development would have been possible without CPRIT funding.”
He says his unique background — becoming a scientific researcher after years in other careers, including in the dot.com industry — “gives me a breadth of knowledge that maybe not everybody brings.”
Hart grew up in northern Texas and received his undergraduate degree in Middle Eastern studies from UT Austin. He had a career in the U.S. government and the private sector before returning to UT Austin as a graduate student in cell & molecular biology, receiving his Ph.D. in 2008. He was a postdoctoral fellow at the Scripps Translational Science Institute, and later at the University of Toronto beginning in 2012.
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