Brendan D. Manning, PhD
Professor, Department of Genetics and Complex Diseases, Harvard School Of Public Health
DF/HCC Program AffiliationCancer Cell BiologyKidney Cancer
Lab WebsiteManning Lab Homepage
Research in the Manning laboratory is aimed at characterizing biochemical links between cellular signaling pathways involved in tumor development and those controlling central metabolism. The goal of this research is to understand the role of oncogenes and tumor suppressors in coordinating cellular signaling events propagated by growth factors, the availability of energy and nutrients, and exposure to environmental stresses. The ability to properly perceive and integrate these signals at both the cellular and organismal levels is essential for the prevention of tumorigenesis and the maintenance of metabolic homeostasis. To elucidate the detailed mechanisms of pathways involved in these processes, the laboratory uses a multi-tiered approach involving bioinformatics, biochemistry, cell biology, genetics, and animal models. We are particularly interested in pathways controlling and controlled by the products of the tumor suppressor genes, TSC1 and TSC2, mutated in the diseases tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM). Our work in this field has defined the molecular link between these tumor suppressors and control of the mammalian target of rapamycin (mTOR) by the PI3K-Akt pathway. Using cell and mouse models, we are investigating the contribution of this pathway to the many cancers exhibiting aberrant activation of the PI3K-Akt pathway, with a focus on its impact on tumor cell metabolism.
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