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Sergiu P. Pasca
Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences and Bonnie Uytengsu and Family Director of the Stanford Brain Organogenesis Program
Current Research and Scholarly InterestsA critical challenge in understanding the intricate programs underlying development, assembly and dysfunction of the human brain is the lack of direct access to intact, functioning human brain tissue for detailed investigation by imaging, recording, and stimulation.
To address this, we are developing bottom-up approaches to generate and assemble, from multi-cellular components, human neural circuits in vitro and in vivo.
We introduced the use of instructive signals for deriving from human pluripotent stem cells self-organizing 3D cellular structures named brain region-specific spheroids/organoids. We demonstrated that these cultures, such as the ones resembling the cerebral cortex, can be reliably derived across many lines and experiments, contain synaptically connected neurons and non-reactive astrocytes, and can be used to gain mechanistic insights into genetic and environmental brain disorders. Moreover, when maintained as long-term cultures, they recapitulate an intrinsic program of maturation that progresses towards postnatal stages.
We also pioneered a modular system to integrate 3D brain region-specific organoids and study human neuronal migration and neural circuit formation in functional preparations that we named assembloids. We have actively applied these models in combination with studies in long-term ex vivo brain preparations to acquire a deeper understanding of human physiology, evolution and disease mechanisms.
We have carved a unique research program that combines rigorous in vivo and in vitro neuroscience, stem cell and molecular biology approaches to construct and deconstruct previously inaccessible stages of human brain development and function in health and disease.
We believe science is a community effort, and accordingly, we have been advancing the field by broadly and openly sharing our technologies with numerous laboratories around the world and organizing the primary research conference and the training courses in the area of cellular models of the human brain.
Emma Pfeiffer Merner Professor of Medical Sciences
Current Research and Scholarly InterestsThe major focuses of our research is to understand the molecular basis of inherited Parkinson's Disease (PD) and to elucidate the molecular mechanisms by which proteins and cholesterol are transported between specific membrane compartments. We focus on the LRRK2 kinase that is inappropriately activated in PD and how it phosphorylates Rab GTPases, blocking the formation of primary cilia in culture and specific regions of the brain.
Sutardja Chuk Professor of Definitive and Curative Medicine
BioDr. Porteus was raised in California and was a local graduate of Gunn High School before completing A.B. degree in “History and Science” at Harvard University where he graduated Magna Cum Laude and wrote an thesis entitled “Safe or Dangerous Chimeras: The recombinant DNA controversy as a conflict between differing socially constructed interpretations of recombinant DNA technology.” He then returned to the area and completed his combined MD, PhD at Stanford Medical School with his PhD focused on understanding the molecular basis of mammalian forebrain development with his PhD thesis entitled “Isolation and Characterization of TES-1/DLX-2: A Novel Homeobox Gene Expressed During Mammalian Forebrain Development.” After completion of his dual degree program, he was an intern and resident in Pediatrics at Boston Children’s Hospital and then completed his Pediatric Hematology/Oncology fellowship in the combined Boston Chidlren’s Hospital/Dana Farber Cancer Institute program. For his fellowship and post-doctoral research he worked with Dr. David Baltimore at MIT and CalTech where he began his studies in developing homologous recombination as a strategy to correct disease causing mutations in stem cells as definitive and curative therapy for children with genetic diseases of the blood, particularly sickle cell disease. Following his training with Dr. Baltimore, he took an independent faculty position at UT Southwestern in the Departments of Pediatrics and Biochemistry before again returning to Stanford in 2010 as an Associate Professor. During this time his work has been the first to demonstrate that gene correction could be achieved in human cells at frequencies that were high enough to potentially cure patients and is considered one of the pioneers and founders of the field of genome editing—a field that now encompasses thousands of labs and several new companies throughout the world. His research program continues to focus on developing genome editing by homologous recombination as curative therapy for children with genetic diseases but also has interests in the clonal dynamics of heterogeneous populations and the use of genome editing to better understand diseases that affect children including infant leukemias and genetic diseases that affect the muscle. Clinically, Dr. Porteus attends at the Lucille Packard Children’s Hospital where he takes care of pediatric patients undergoing hematopoietic stem cell transplantation.
Associate Professor of Radiation Oncology (Radiation Physics)
Current Research and Scholarly InterestsThe Physical Oncology Lab is interested in making a lasting impact on translational cancer research by building novel physical tools and methods.