Copper-Dependent Nutrient Signaling and Metabolism Vulnerabilities in Cancer
Event Details
- Type
- Friday Lecture Series
- Speaker(s)
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Donita C. Brady, Ph.D., Harrison McCrea Dickson, M.D. and Clifford C. Baker, M.D. Presidential Professor and Assistant Dean for Inclusion, Diversity, and Equity in Research Training, department of cancer biology, University of Pennsylvania Perelman School of Medicine
- Speaker bio(s)
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Akin to organic nutrients, such as oxygen, lipids, amino acids, and carbohydrates, the transition metal copper (Cu) is an essential dietary nutrient for normal physiology and development. Decades of research highlight the physiological and disease associated consequences of disrupting homeostatic mechanisms that ensure proper Cu acquisition, storage, and distribution to Cu-dependent enzymes. However, phenotypes associated with alterations in Cu availability cannot be fully explained by the limited number of enzymes that traditionally harness the redox potential of Cu as a catalytic cofactor. Recent discoveries in Cu biology have revealed direct Cu binding at non-catalytic sites within signaling molecules that modulate cell proliferation via the protein kinases MEK1/2, lipid metabolism via the phosphodiesterase PDE3B, and nutrient recycling via the autophagic kinases ULK1/2. The emergence of this new paradigm in nutrient sensing and protein regulation has established that Cu is a critical mediator of intracellular signaling, provided evidence for the existence of molecular mechanisms for sensing changes in Cu abundance, and expanded the contribution of Cu to cellular processes necessary for adaptation to nutrient scarcity. The Brady Lab's ongoing work focuses on the intersections between Cu homeostasis, nutrient signaling, and metabolism by examining the interplay between mechanisms of Cu-sensing necessary for cellular energy homeostasis and evaluating the necessity of Cu for metabolic flexibility under nutrient and oxygen stress. Specifically, they are elucidating mechanisms of: i) Cu-controlled autophagy-lysosomal biogenesis and function, ii) Cu-mediated metabolic flexibility via direct control of glycolytic flux, and iii) interconnectivity between mitochondrial Cu transport and cytosolic nutrient sensing signaling pathways necessary for metabolism.
Donita C. Brady received her B.S. in Chemistry from Radford University and her Ph.D. in Pharmacology from the University of North Carolina at Chapel Hill. She completed her postdoctoral work with Dr. Christopher Counter at Duke University focusing on pharmacologically accessible signaling pathways downstream of oncogenes, like RAS. Her independent laboratory at Penn is founded in a new paradigm in nutrient sensing and protein regulation, termed metalloallostery, where redox-active metals control kinase activity, and is advancing our knowledge in basic science and disease-focused areas. Their focus lies at the intersection of kinase signaling and copper (Cu) homeostasis with the goal of defining the mechanistic features of Cu-dependent kinases to target them in cancer via drug repurposing or development. Beyond articulating and providing support for this novel hypothesis, Dr. Brady’s mechanistic studies have substantively contributed to our understanding of the unexpected roles of metals in nutrient signaling, cellular energy homeostasis, and metabolic vulnerabilities in cancer. Dr. Brady has received many honors, including being named a Pew Charitable Trust Scholar in the Biomedical Sciences, a William Guy Forbeck Research Foundation Scholar, V Foundation Scholar, and the prestigious Perelman School of Medicine Michael S. Brown New Investigator Research Award. In 2021, Dr. Brady was appointed as the inaugural Assistant Dean for Inclusion, Diversity, and Equity (IDE) in Research Training at the Perelman School of Medicine and serves as the faculty lead of the IDEAL (Inclusion, Diversity, Equity, and Learner) Research office that supports the Perelman School of Medicine diverse community of learners by cultivating a culture of equitable inclusivity across all education programs.
FLS lectures will take place in Caspary Auditorium and virtually via Zoom. We recommend virtual participants log out of VPN prior to logging in to Zoom. Please do not share the link or post on social media. This talk will be recorded for the RU community.
- Open to
- Tri-Institutional