Sergiu P. Pașca

Sergiu P. Pașca(born January 30, 1982) is aRomanian-Americanscientist andphysicianatStanford Universityin California. He is renowned for his groundbreaking work creating and developing stem cell-based models of the human brain to gain insights into neuropsychiatric disease. His lab was the first to develop and nameassembloids: multi-unit self-organizing structures created in 3D cultures that allow for the study of human neural circuit and systems functionsin vitro.Pașca’s lab generated and published human cortico-striataland cortico-motorassembloids in 2020. Combining regionalized neural organoids pioneered in the lab and studies with human forebrain assembloidsand transplantation, in 2024, Pașca developed a therapeutic for a severe genetic disorder calledTimothy Syndrome,which was published on the cover ofNature.
Pașca is a pioneering neuroscientist and stem cell biologist and holds the Kenneth T. Norris Endowed Professorship in Psychiatry and Behavioral Sciences atStanford University.He founded and leads the Stanford Brain Organogenesis Programas the Bonnie Uytengsu and Family Founding Director. He is part of the Stanford Neurosciences Institute, Stanford Bio-X and he is a fellow of the ChEM-H Institute at Stanford.Pașca was listed amongNew York TimesVisionaries in Medicine and Sciences, he is the recipient of the 2018 Vilcek Award for Creative Biomedical Promise from theVlicek Foundation,and the 2022IBRO-Kemali Neuroscience Prize,and he holds aDoctor Honoris Causa.In 2022, he gave aTEDtalk on reverse engineering the human brain in the laboratoryand in 2023 he became a Knight of theOrder of Merit of Romania.
Pașca was born inCluj-Napoca, in the region ofTransylvania. He was raised in nearbyAiudduring the last years ofcommunism.Pașca showed early on an interest inchemistry. He set up his first science lab at the age of 11, in the basement of his parents’ house.In the final year of high school, he won a prize in the nationalchemistry Olympiad, earning a scholarship to attend the university of his choice in Romania. In 2001, Pașca enrolled in theIuliu Hațieganu University of Medicine and Pharmacyat Cluj-Napoca.As a medical student, he worked with Professor Maria Dronca to explore biochemical defects inautism spectrum disorders. At the same time, he studiedelectrophysiologyat theMax Planck Institute for Brain ResearchinFrankfurtin Germany under Dr Danko Nikolic. After obtaining his M.D. in 2007, Pașca went to Stanford University in early 2009 as apostdoctoral fellowwith ProfessorRicardo Dolmetsch. At Stanford, he developed methods to deriveneuronsfrominduced pluripotent stem cells(iPSC) and used these neural cultures to identify cellularphenotypesassociated withbrain disorders, includingTimothy syndromeandDravet syndrome.
In 2014, he was recruited as a tenure-track Assistant Professor at Stanford University and opened his own laboratory.He became a tenured Associate Professor in 2020 and full Professor in 2022. He was soon after named an Endowed Professor at Stanford University.
In 2023, he received a Doctor Honoris Causa (D.H.C.) fromIuliu Hatieganu Medical Schoolin Cluj-Napoca, Romania.
His personal trajectory was described in aQuantaprofileby the American journalistClaudia Dreyfus.
Pașca has two children.
Pașca’s laboratory at Stanford University explores the biological mechanisms ofneurodevelopmental disorders, such asautismspectrum disorders,epilepsyandschizophrenia, using cellular models of the human brain.Pașca developed some of the early in-a-dish models of disease by deriving neurons from skin cells taken from patients with genetic forms of autism and other neurodevelopmental disorders.These patient neurons helped uncover the cellular defects of genetic mutations and demonstrated the promise of this novel technology. In 2024, his lab reported a therapeutic developed exclusively with human stem cell-based models.
Neural organoids
In his laboratory, Pașca introduced the use of instructive signals to develop lab-grown self-assembling three-dimensional (3D) structures called regionalized neural spheroids ororganoids.Through application of various guidance molecules, Pașca ’s lab has developed about a dozen distinct neural organoids representing different brain areas, including thecerebral cortex, ventral forebrain,striatum,spinal cord,thalamusand others. This method was listed among the Key Advances in hiPSC Disease Modeling of the Last Decade by the journalCell Stem Cell,and Organoids were named Methods of the Year in 2017 byNature Methods.These 3D brain tissue resemble specific regions of the nervous systemand his laboratory has maintained these cultures for over 1000 daysin vitroand demonstrated advanced cell maturation, includingastrocytes, into postnatal stages according to an intrinsic clock. His work on astrocytes was inspired by the late Stanford neurobiologistBen Barres.
Assembloids
Pașca has demonstrated that brain-region specific organoids can be fused to form brainassembloids, which spontaneously integrate and demonstrate emergent properties. He has employed this preparation to study the cross-talk between cells in the developing human brain and to mimic human brain circuits in a dish. Pașca coined the termassembloidsin 2018referring to the first forebrain assembloids developed in early 2017.This work was listed among the Top Research Advances of 2017 by theNational Institutes of Health.His lab has subsequently developed cortico-striataland three-part cortico-spinal-muscle assembloids.By combining assembloids withCRISPRscreening, Pașca lab mapped hundreds of autism-related genes tointerneurondevelopment stages, which also revealed an unknown role of theendoplasmic reticulumin migration.
In 2024, his lab reported the first four-partassembloidsthat model the somatosensory pathway,enabling activity monitoring of the entire circuit and response to noxious stimuli. Assembloids are now widely used to model complex cell-cell interactions in other systems and organs, including the gut, immune system, cancer, etc.
Assembloids have been useful for studying neural migration, circuit formation, and unveiling a surprising ability of neural circuits to self-assemble,ex vivo, from parts.
Transplantation of organoids
In 2022, his group demonstrated the successful integration of human cortical organoids into the developing rat cerebral cortex. Human neurons displayed advanced maturationin vivo, responded to whisker stimulation and were capable of influencing the behavior of the rat in a reward task.
This work was extensively covered by the press.Pașca discussed the ethical implications of his work with the ethicistInsoo Hyunin a video materialfilmed at theBoston Science Museum. Pașca acknowledged that organoid transplantation offers great promise for characterizing human cellular processesin vivobut encourages caution and ethical consideration in pursuing these experiments.
Stanford Brain Organogenesis
In 2019, Pașca founded theStanford Brain Organogenesis Program, which is a university wide effort to leverage technologies developed at Stanford to advance our understanding of human brain development and circuit assembly. The program includesKarl Deisseroth,Zhenan Bao,Bianxiao Cui,Michael Lin, Sarah Heilshorn andHank Greely. Pașca serves as the Bonnie Uytengsu and Family Director. The program is also broadly sharing organoid and assembloids technologies through a free, hands-on course course that brings student from all over the world.
Teaching and public engagement
At Stanford, Pașca teaches neural development and principles of drug discovery in neuroscience. Pașca is also the co-director of the CSHL Workshop on autism spectrum disorders.
In 2022, he gave a TED talkat the Vancouver event describing the potential of human cellular models to understand disease.
Pașca is aChan Zuckerberg InitiativeBen BarresInvestigator and aCZ BioHubInvestigator. He was aNew York Stem Cell FoundationRoberston Stem Cell Investigator. His researched activity gained him several awards:
In Romania, he was recognized as the Best Romanian student studying abroad in 2012.