Using Stem Cells to Explore the Genetics Underlying Brain Disease

BNA Event - 25th May 2022

We invite you to join this FREE joint webinar between Biotechne/Tocris and the BNA, taking place on Wednesday 25th May, 1-2pm (BST)

Kristen Brennand, PhD is a Professor of Psychiatry and Genetics at Yale University School of Medicine, formerly the Director of the Alper Neural Stem Cell Center and an Associate Professor in the Pamela Sklar Division of Psychiatric Genomics at Mount Sinai. Her research combines expertise in genetics, neuroscience and stem cells, in order to identify the mechanisms that underlie brain disease. Her focus lies in resolving the convergence of, and complex interplay between, the many risk variants linked to disease, towards the goal of facilitating the clinical translation of genetic findings. Dr. Brennand’s work is funded by the National Institutes of Health, the New York Stem Cell Foundation, the Brain Research Foundation, and the Brain and Behavior Research Foundation.

Talk abstract:

Combining expertise in stem cell biology, neurobiology, and psychiatric genomics, we helped to pioneer a new approach by which to study brain disease, establishing that genetic predisposition to psychiatric disorders ranging from schizophrenia to bipolar disorder to autism spectrum disorder can be modeled using patient-specific human induced pluripotent stem cells (hiPSCs). Today, my laboratory integrates hiPSC-based approaches with CRISPR-mediated genomic engineering strategies, in order to study the impact of patient-specific variants across and between the cell types of the brain. Our highly collaborative approach strives to uncover the convergence and synergy arising from the complex interplay of the many risk variants linked to brain disease.

Each person’s distinct genetic, epigenetic, and environmental risk profile predisposes them to some phenotypes and confers resilience to others. My laboratory seeks to decode highly complex genetic insights into medically actionable information, better connecting the expanding list of genetic loci associated with human disease to pathophysiology. Our goal is to improve diagnostics, predict clinical trajectories, and identify pre-symptomatic points of therapeutic intervention. Towards this, we employ a functional genomics approach that integrates stem cell models and genome engineering to resolve the impact of patient-specific variants across cell types, genetic backgrounds, and environmental conditions. Individually small risk effects combine to yield much larger impacts in aggregate, but the interactions between the myriad variants remain undetermined. We seek to uncover disease-associated interactions within and between the cell types of the brain, querying the impacts of complex genetic risk within increasingly sophisticated neuronal circuits. Thus, we strive to translate risk “variants to genes”, “genes to pathways”, and “pathways to circuits”, revealing the convergent, additive, and synergistic relationships between risk factors within and between the cell types of the brain.

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