James Broach, Ph.D.
Dr. Broach is Chair of the Department of Biochemistry and Molecular Biology at Penn State Hershey and the Director of the Penn State Institute for Personalized Medicine and Professor Emeritus of Princeton University. He completed his undergraduate studies in Chemistry at Yale University in 1969 and his Ph.D. in Biochemistry from the University of California, Berkeley in 1973, where he also completed a Postdoctoral Fellowship in Medical Physics. Dr. Broach served on the Scientific Review Board of the Frederick Cancer Center of the National Cancer Institute and has served as a member of both the Genetics and the Genomics Study Sections and Chair of the Genomics, Computational Biology and Technology Study Section of the National Institutes of Health. He was Co-Founder and Director of Research for Cadus Pharmaceuticals and sits on the Board of Directors of Cadus Corporation.
Dr. Broach was Professor of Molecular Biology at Princeton University from 1984-2012, where he served as Associate Director of the Lewis Sigler Institute for Integrative Genomics and Co-Director of the Center for Computational Biology. Dr. Broach is a Fellow of the American Academy of Microbiology and the Co-Director of the Life Sciences Research Foundation, a private organization that provides postdoctoral fellowships in the life sciences. Dr. Broach is a member of the Science Board of the Food and Drug Administration and served as Trustee of the University of Medicine and Dentistry of New Jersey and Commissioner on the New Jersey Commission on Cancer Research until 2012. He is a member of the executive committee of the Cancer Biology Training Consortium, a national organization promoting graduate and postdoctoral training in cancer biology. Dr. Broach has published more than 150 articles in the area of molecular biology and holds a number of patents in drug discovery technologies.
Lab Phone: 717-531-5996
Broach Lab Links
Broach Lab Research
Research in the Broach lab addresses the fundamental question of how cells regulate their growth and development in response to environmental conditions, such as their nutritional status and external stress. Two major nutrient sensing networks – the Ras/protein kinase A (PKA) pathway and the rapamycin-sensitive TORC1 – link nutrient status to cellular processes, including ribosome biogenesis and growth, autophagy, stress response and entry into quiescence. Our studies have led us to the unexpected conclusion that yeast cells make their growth decisions on the basis of their perception of nutrient availability, as monitored through these signaling networks, rather than on the basis of their use of those nutrients. Consistent with that interpretation, activating alleles of Ras in yeast drive a proliferative program even in the absence of nutrients. This observation resonates with the fact that oncogenic, activating mutations of ras in mammalian cells drive cells into proliferation in spite of external countervailing signaling enjoining the cells to stop growing. Thus, besides addressing the fundamental question of control of cell growth, our ongoing studies into the means by which input from these two pathways yield a coherent growth response highlight means by which higher cells integrate external cues and address how manipulation of signaling networks can be leveraged to achieve therapeutic ends.
Regulation of metabolism through signaling networks. Central to cell growth is the metabolism of nutrients, which generates energy, creates building blocks for macromolecular biosynthesis and promotes synthesis of the panoply of chemical entities that are needed to make two cells from one. We have found that signaling pathways impinge on metabolic enzymes, not only as regulators of the transcript levels and stability of the proteins but also as regulators of enzymatic activity through post-translational modifications. Many such post-translational modifications have been identified and studied, including rate limiting steps in the glycolyic pathway regulated by PKA in yeast. We continue to study, though a marriage of molecular genetics, proteomic and metabolomic methods, how these posttranslational modifications affect metabolic flow in the cell.
Cellular stress response. All cells perceive and respond to environmental stresses and that response is critical to a cell’s survival under continued adverse conditions. In yeast cells, a number of sensing pathways provide input regarding potentially stressful environmental conditions and converge on stress sensitive transcription factors, one of which is encoded redundantly by MSN2 and MSN4. These transcription factors serve as foci through which cells integrate information on their environmental state and develop responses that are appropriate to that state. By examining the response of individual cells to stress in microfluidic devices, we have defined the network of signaling pathways transmitting the stress response. We have established that noise in the signaling network permits genetically identical cells to mount different responses to identical stimuli, a process that allows populations of cells to “hedge their bets” with regard to survival strategies in a changing and unpredictable environment.
Quiescence – the essence of chronological aging. Under prolonged stress or sustained starvation, cells exit the proliferation state and enter a poorly defined quiescence state. Mammalian cells such as fibroblasts, stem cells and memory T and B lymphocytes can exit the proliferative state in response to specific cues and enter a quiescent state called G0 to indicate that this state is distinct from any that are traversed during the normal cell cycle. Despite the ubiquity and importance of quiescence, we have little understanding of the nature or this state or the means by which cells transit into and out of it. We are using a combination of highly parallel genetic screens in conjunction with proteomic and phosphoproteomic analysis to define the essential characteristics of quiescence and identify the means of inducing entry and exit from that state. Analysis in yeast of chronological lifespan, the functional equivalent of quiescence, has been uncannily predictive of processes that influence lifespan in mammalian organisms. Thus, understanding the forces that regulate entry and exit from quiescence could profoundly affect our ability to manipulate lifespan in mammalian species such as ourselves.