Global Speaker Series: Robert Signer, PhD – University of California, San Diego

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The Medicine by Design Global Speaker Series invites established and emerging international leaders in regenerative medicine to engage with our extraordinary community of researchers and clinicians.

Medicine by Design, in partnership with the McEwen Stem Cell Institute, is pleased to welcome Robert Signer, PhD. Dr. Signer is Deputy Director of the Stem Cell Discovery Center and an Associate Professor of Medicine in the Division of Regenerative Medicine at the University of California San Diego.

Hosted by Medicine by Design, in partnership with the McEwen Stem Cell Institute. 

Talk title: “Stem Cell Fitness & Longevity: The Role of Proteostasis 

This event will be held in-person only at the Terrence Donnelly Centre for Cellular & Biomolecular Research, Red Room.

About Robert Signer

Dr. Robert Signer is a stem cell biologist whose trailblazing work on protein synthesis and homeostasis in blood-forming stem cells opened the door to unchartered areas of cellular investigation. Dr. Signer is currently the Deputy Director of the Sanford Stem Cell Discovery Center and an Associate Professor of Medicine in the Division of Regenerative Medicine at UC San Diego. 

Previously, Dr. Signer trained as a Postdoctoral Fellow at the UT Southwestern Medical Center. He earned a Ph.D. in Cellular and Molecular Pathology at UCLA, and a Bachelor’s in Engineering Science from the University of Toronto. His discoveries have been recognized by numerous awards from the Leukemia and Lymphoma Society, the V Foundation for Cancer Research, and the California Institute for Regenerative Medicine, among others. He was named a Distinguished International Young Investigator in Stem Cell Research and is the 2024 recipient of the prestigious Janet Rowley Award from the International Society of Experimental Hematology. 

Talk abstract

Hematopoietic stem cells (HSCs) persist throughout life to regenerate blood cells lost to physiological turnover, injury and disease. But how stem cells preserve their immense regenerative potential while simultaneously sustaining their remarkable longevity remains a mystery. The regulation of protein homeostasis (proteostasis) has emerged as being fundamentally and preferentially important for HSCs. Proteostasis is maintained by an integrated network of physiological mechanisms and stress response pathways that coordinate protein synthesis, folding, trafficking and degradation to regulate the content and quality of the proteome. Many of these highly-conserved pathways have long been thought of as housekeeping functions, performed similarly by most cells. However, we found that HSCs exhibit unique cell-type-specific configuration of the proteostasis network that is critical for preserving their fitness, health and longevity. Young adult HSCs exhibit unusually low protein synthesis rates to restrict the biogenesis of misfolded proteins in vivo and utilize non-canonical protein trafficking and degradation pathways to limit the accumulation of protein aggregation to preserve their long-term self-renewal potential. Challenges to proteostasis during aging cause HSCs to remodel their proteostasis network to sustain their fitness and regenerative potential. However, adapting to these selective pressures comes at the cost of increasing the risk of premalignant and malignant disease. Overall, unique and dynamic regulation of proteostasis is key for balancing stem cell regeneration and longevity.

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