PINS: The multifaceted roles of TSC-mTOR signaling in neural development, function and disease

Helen Bateup, PhD Associate Professor of Neurobiology UC Berkeley Research in my lab broadly aims to understand the cellular and molecular basis of neuropsychiatric disorders. We have a particular interest in “mTORopathies”, which are developmental brain disorders caused by mutations in the mTOR signaling pathway that lead to epilepsy, intellectual disability, and increased risk for autism spectrum disorder. To elucidate disease mechanisms for these disorders, we use genetically-defined mouse and human cellular models in combination with a variety of techniques spanning molecular profiling to behavioral analysis. Our goal is to generate a mechanistic understanding of how disease-associated mutations affect the cell biology and physiology of specific types of neurons, and how altered neuronal activity impacts circuit function and behavior. In addition, we are investigating the early developmental alterations that may contribute to mTOR-related disorders using genetically engineered and patient-derived human brain organoids. Tsc1-mTORC1 signaling controls striatal dopamine release and cognitive flexibility Kosillo P, Doig NM, Ahmed KM, Agopyan-Miu AHCW, Wong CD, Conyers L, Threlfell S, Magill PJ, and Bateup HS Nature Communications. November 28, 2019. PMID: 31780742 Genetically engineered human cortical spheroid models of tuberous sclerosis Blair JD, Hockemeyer D, and Bateup HS Nature Medicine. October 24, 2018. PMID: 30127391 Corticostriatal Transmission Is Selectively Enhanced in Striatonigral Neurons with Postnatal Loss of Tsc1 Benthall KN, Ong SL, Bateup HS Cell Reports. June 12, 2018. PMID: 29898392