Joan and Irwin Jacobs Endowed Chair in Bioengineering and Systems Biology
Distinguished Professor of Bioengineering, Computer Science and Engineering, Cellular and Molecular Medicine, and NanoEngineering
University of California San Diego
Title: Neurons in pathology through the lens of multi-omics and data analytics
Abstract: Advances in stem cell engineering, omics technologies and data sciences offer a unique scope for deciphering the myriad ways molecular circuits dysfunction in pathologies of the brain. Recently, we have developed and explored iPSC-derived neurons from familial Alzheimer’s disease patients using a systems-level, multi-omics approach, identifying disease-related endotypes, which are commonly dysregulated in patient-derived neurons and patient brain tissue alike. By integrating RNA-Seq, ATAC-Seq, and ChIP-Seq approaches, we determined that the defining disease-causing mechanism of AD is de-differentiation of neurons, driven primarily through the REST-mediated repression of neuronal lineage specification gene programs and the activation of cell cycle reentry and non-specific germ layer precursor gene programs concomitant with modifications in chromatin accessibility. Strikingly, our reanalysis of previously-generated AD-patient brain tissue showed similar enrichment of neuronal repression and de-differentiation mechanisms. Surprisingly, our earlier work on glioblastoma also showed de-differentiation and initiation of some of the shared diseased endotypes as common features. We postulate that de-differentiation and reprogramming are hallmark mechanisms of numerous pathologies, arguably genetically evolved to serve as protection mechanisms.
Bio: Shankar Subramaniam is a Distinguished Professor of Bioengineering, Computer Science and Engineering, Cellular and Molecular Medicine, Chemistry and Biochemistry and Nano Engineering. He holds the inaugural Joan and Irwin Jacobs Endowed Chair in Bioengineering and Systems Biology. He is a Fellow of the AIMBE and AAAS and the current President of IEEE EMBS. He has numerous awards for this scientific contributions including the UCSD Faculty Excellence Award for Research, the Genome Technology All Star Award, the Association of Lab Automation Award, and the Smithsonian Foundation Innovation in Computing Award.