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MSL Faculty Candidate Seminar: Dr. Kathlyn Gan
February 4, 2020 @ 9:00 am - 10:00 am
The Michael Smith Laboratories presents a faculty candidate seminar:
Dr. Kathlyn Gan
Department of Molecular and Cellular Physiology
Date: Tuesday, February 4th
Time: 9:00 AM
Location: MSL Auditorium (MSL 102) – 2185 East Mall
Title: Specific factors enriched in young blood directly promote synapse formation and activity in human neurons
Abstract: Synapses, the connections between neurons that enable information processing and memory storage, decline in number and function as we age. This loss of synaptic connectivity leads to cognitive impairment and predisposes healthy individuals to neurodegenerative diseases. Pioneering experiments showed that exposure of aged mice to young blood reversed impairments in learning and memory. Building upon those findings, I differentiated human neurons from embryonic stem cells and treated them with serum extracted from young and aged mice (“young blood” and “old blood”, respectively). Using electrophysiology and immunocytochemistry, I discovered that young but not old blood dramatically increased synapse formation and activity. Using mass spectrometry and biochemistry, I identified secreted proteins enriched in young blood, including the extracellular matrix proteins thrombospondin-4 (THBS4) and SPARC-like protein-1 (SPARCL1). Treatment of human neurons with recombinant THBS4 and SPARCL1 recapitulated the benefits of young blood and even enhanced synapse formation in neurons cultured previously with old blood. Experiments are in progress to identify downstream cell-surface receptors and effectors that mediate synapse formation and to determine if THBS4 and SPARCL1 rejuvenate synaptic connectivity in vivo. Results will inform a high-throughput screen for novel, small molecule enhancers of synapse formation in aging human neurons. Collectively, this research will be important for defining molecular mechanisms that drive changes in synaptic connectivity during healthy aging, for understanding how their perturbation drives neurodegeneration, and for developing effective disease therapeutics.