Sergiu P. Pașca

Sergiu P. Pașca (born January 30, 1982) is a Romanian-American scientist and physician at Stanford University in California. He is known for creating and developing stem cell-based models of the human brain and applying organoids and assembloids to gain insights into neuropsychiatric disease.

Sergiu P. Pașca
Pașca in 2018
Born(1982-01-30)January 30, 1982
NationalityAmerican & Romanian
Alma materIuliu Hațieganu University of Medicine and Pharmacy
Scientific career
FieldsNeuroscience, Biology, Stem Cell
InstitutionsStanford University
Academic advisorsRicardo Dolmetsch
Websitewww.pascalab.org

Pașca is the Kenneth T. Norris Endowed Professor of Psychiatry and Behavioral Sciences at Stanford University[1] and the Bonnie Uytengsu and Family Founding Director of Stanford Brain Organogenesis,[2] a neuroscientist and stem cell biologist. He is part of the Stanford Neurosciences Institute, Stanford Bio-X and a fellow of the ChEM-H Institute at Stanford.[1] Pașca was listed among New York Times Visionaries in Medicine and Sciences, he is the recipient of the 2018 Vilcek Award for Creative Biomedical Promise from the Vlicek Foundation[3], and the 2022 IBRO-Kemali Neuroscience Prize[4], and he holds a Doctor Honoris Causa[5]. In 2022, he gave a TED talk on reverse engineering the human brain in the laboratory[6] and in 2023 he became a Knight of the Order of Merit[7].

Early life and education

Pașca was born in Cluj-Napoca in the western part of Romania also known as Transylvania. He was raised in nearby Aiud during the last years of communism.[8] Pașca showed early on an interest in chemistry. He set up his first science lab at the age of 11, in the basement of his parents’ house.[9] In the final year of high school, he won a prize in the national chemistry Olympiad, earning a scholarship to attend the university of his choice in Romania. In 2001, Pașca enrolled in the Iuliu Hațieganu University of Medicine and Pharmacy at Cluj-Napoca.[1] As a medical student, he worked with Professor Maria Dronca to explore biochemical defects in autism spectrum disorders. At the same time, he studied electrophysiology at the Max Planck Institute for Brain Research in Frankfurt in Germany under Dr Danko Nikolic. After obtaining his M.D. in 2007, Pașca went to Stanford University in early 2009 as a postdoctoral fellow with Professor Ricardo Dolmetsch. At Stanford, he developed methods to derive neurons from induced pluripotent stem cells (iPSC) and used these neural cultures to identify cellular phenotypes associated with brain disorders, including Timothy syndrome and Dravet syndrome.[10][11][12][13]

Research

Pașca’s laboratory at Stanford University explores the biological mechanisms of brain disorders using cellular models of the human brain.[14] 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.[15][16] These patient neurons helped uncover the cellular defects of genetic mutations and demonstrated the promise of this novel technology. In his laboratory, Pașca went further to develop a novel platform that allows to take iPSC from any individuals and engineer lab-grown self-assembling three-dimensional (3D) structures called brain region-specific spheroids or organoids.[17] This method was listed among the Key Advances in hiPSC Disease Modeling of the Last Decade by the journal Cell Stem Cell,[18] and Organoids were named Methods of the Year in 2017 by Nature Methods.[19] These 3D brain tissue resemble specific regions of the nervous system[20][21] and his laboratory has maintained these cultures for over 800 days in vitro to show maturation of cells, including astrocytes, into postnatal stages. His work on astrocytes was inspired by the late Stanford neurobiologist Ben Barres. Pașca has also demonstrated that brain-region specific organoids can be fused to form brain assembloids and employed this preparation to study the cross-talk between cells in the developing human brain and to mimic human brain circuits in a dish.[22] This work was listed among the Top Research Advances of 2017 by the National Institutes of Health.[23] In 2022, his group demonstrated the successful integration of human cortical organoids into the developing rat cerebral cortex. Human neurons displayed advanced maturation in vivo, responded to whisker stimulation and were capable of influencing the behavior of the rat in a reward task.[24]

Pașca is the co-director of the CSHL Workshop on autism spectrum disorders.[25]

Honors

Pașca is a New York Stem Cell Foundation Roberston Stem Cell Investigator, a Chan Zuckerberg Initiative Ben Barres Investigator and a CZ BioHub Investigator. His researched activity gained him several awards:

  • IBRO Dargut and Milena Kemali International Prize for Basic and Clinical Neurosciences (2022)[26]
  • Judson Daland Prize for Outstanding Achievement in Clinical Investigation, American Society of Philosophy (2021)[27]
  • Joseph Altman Award in Developmental Neuroscience (2021)[28]
  • Schizophrenia Basic Research Award (2021)[29]
  • C.J. Herrick Award in Neuroanatomy (2020)
  • A.E.Bennett Award, Society of Biological Psychiatry (2018)[30]
  • Daniel H. Efron Award, American College of Neuropsychopharmacology (2018)[31]
  • Günter Blobel Award, American Society of Cell Biology (2018)[32]
  • New York Times Visionaries in Science and Medicine (2018)[33]
  • Vilcek Award for Creative Biomedical Promise (2018)[34]
  • Jordi Folch-Pi Award, American Society for Neurochemistry (2017)[35]
  • NARSAD Independent Investigator Award (2017)[36]
  • NIMH Director's BRAINS Award (2015)
  • MQ Fellow Award for Transforming Mental Health (2014)[37]
  • Sammy Kuo Award (2012)[38]
  • IBRO Outstanding Research Fellow (2009)

In Romania, he was recognized as the Best Romanian student studying abroad in 2012.[39]

References

  1. "Sergiu P. Pașca's Profile | Stanford Profiles". Profiles.stanford.edu. Retrieved 2018-06-07.
  2. "Stanford Brain Organogenesis Program". 8 October 2018.
  3. Lisa M. Krieger (February 1, 2018). "Stanford scientist wins award for immigrant scientists". The Mercury News. Retrieved January 13, 2018.
  4. admin (2021-09-20). "IBRO-Kemali Prize Awarded to Dr. Sergiu P. Pasca". IBRO. Retrieved 2023-10-23.
  5. "Sergiu Pașca a primit titlul de Doctor Honoris Causa al UMF Cluj. Fostul student al universității, un lider internațional în neuroștiințe: „E important ca tinerii să se pregătească în străinătate și să se întoarcă în țară"". monitorulcj.ro (in Romanian). 2023-04-29. Retrieved 2023-10-23.
  6. "Sergiu P. Pasca: How we're reverse engineering the human brain in the lab". 24 August 2022.
  7. "Stanford University researcher Sergiu Pasca decorated by President Klaus Iohannis". Stiri pe surse. 2023-03-28. Retrieved 2023-10-23.
  8. "The Vilcek Foundation - Sergiu P. Pașca". www.vilcek.org. Retrieved 7 June 2018.
  9. "Rising Star: Sergiu Pașca, scientist at play | Spectrum | Autism Research News". Spectrum | Autism Research News. 19 February 2015. Retrieved 7 June 2018.
  10. Krey, Jocelyn F.; Pașca, Sergiu P.; Shcheglovitov, Aleksandr; et al. (2013). "Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons". Nature Neuroscience. 16 (2): 201–209. doi:10.1038/nn.3307. ISSN 1546-1726. PMC 3568452. PMID 23313911.
  11. Paşca, Sergiu P.; Portmann, Thomas; Voineagu, Irina; et al. (27 November 2011). "Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome". Nature Medicine. 17 (12): 1657–1662. doi:10.1038/nm.2576. ISSN 1546-170X. PMC 3517299. PMID 22120178.
  12. Sun, Yishan; Paşca, Sergiu P; Portmann, Thomas; et al. (26 July 2016). "A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients". eLife. 5. doi:10.7554/eLife.13073. ISSN 2050-084X. PMC 4961470. PMID 27458797.
  13. Tian, Yuan; Voineagu, Irina; Paşca, Sergiu P.; et al. (2014). "Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome". Genome Medicine. 6 (10): 75. doi:10.1186/s13073-014-0075-5. ISSN 1756-994X. PMC 4213483. PMID 25360157.
  14. "Pașca Lab @ Stanford University - Home". Pascalab.org. 2018-05-24. Retrieved 2018-06-07.
  15. Paşca, Sergiu P.; Panagiotakos, Georgia; Dolmetsch, Ricardo E. (2014). "Generating human neurons in vitro and using them to understand neuropsychiatric disease". Annual Review of Neuroscience. 37: 479–501. doi:10.1146/annurev-neuro-062012-170328. ISSN 1545-4126. PMID 25002278.
  16. "The Vilcek Foundation - Sergiu P. Pașca". Vilcek.org. Retrieved 2018-06-07.
  17. Pașca, Sergiu P. (2018). "The rise of three-dimensional human brain cultures". Nature. 553 (7689): 437–445. Bibcode:2018Natur.553..437P. doi:10.1038/nature25032. ISSN 1476-4687. PMID 29364288. S2CID 205262820.
  18. Passier, Robert; Orlova, Valeria; Mummery, Christine (March 2016). "Complex Tissue and Disease Modeling using hiPSCs". Cell Stem Cell. 18 (3): 309–321. doi:10.1016/j.stem.2016.02.011. PMID 26942851.
  19. "Method of the Year 2017: Organoids". Nature Methods. 15: 1. 3 January 2018. doi:10.1038/nmeth.4575.
  20. Paşca, Anca M.; Sloan, Steven A.; Clarke, Laura E.; et al. (2015). "Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture". Nature Methods. 12 (7): 671–678. doi:10.1038/nmeth.3415. ISSN 1548-7105. PMC 4489980. PMID 26005811.
  21. Sloan, Steven A.; Darmanis, Spyros; Huber, Nina; et al. (16 August 2017). "Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells". Neuron. 95 (4): 779–790.e6. doi:10.1016/j.neuron.2017.07.035. ISSN 1097-4199. PMC 5890820. PMID 28817799.
  22. Birey, Fikri; Andersen, Jimena; Makinson, Christopher D.; et al. (2017). "Assembly of functionally integrated human forebrain spheroids". Nature. 545 (7652): 54–59. Bibcode:2017Natur.545...54B. doi:10.1038/nature22330. ISSN 1476-4687. PMC 5805137. PMID 28445465.
  23. "2017 Research Highlights — Insights from the Lab". National Institutes of Health (NIH). 15 December 2017. Retrieved 7 June 2018.
  24. Revah, Omer; Gore, Felicity; Kelley, Kevin W.; Andersen, Jimena; Sakai, Noriaki; Chen, Xiaoyu; Li, Min-Yin; Birey, Fikri; Yang, Xiao; Saw, Nay L.; Baker, Samuel W.; Amin, Neal D.; Kulkarni, Shravanti; Mudipalli, Rachana; Cui, Bianxiao (2022-10-13). "Maturation and circuit integration of transplanted human cortical organoids". Nature. 610 (7931): 319–326. Bibcode:2022Natur.610..319R. doi:10.1038/s41586-022-05277-w. ISSN 0028-0836. PMC 9556304. PMID 36224417.
  25. "Workshop on Autism Spectrum Disorders | CSHL". meetings.cshl.edu. Retrieved 2022-04-14.
  26. "IBRO-Kemali Prize Awarded to Dr. Sergiu P. Pasca". IBRO. 2021-09-20. Retrieved 2022-05-15.
  27. "2021 Judson Daland Prize". American Philosophical Society. Retrieved 2022-05-15.
  28. "Announcement of the Awardee of the 2021 Joseph Altman Award in Developmental Neuroscience". The Japan Neuroscience Society. Retrieved 2022-05-15.
  29. "2021 Basic Research Award | Schizophrenia International Research Society". Retrieved 2022-05-15.
  30. "A.E. Bennett Basic Research Award | Society of Biological Psychiatry". Retrieved 2022-05-15.
  31. "Daniel H. Efron Research Previous Award Winners". ACNP. Retrieved 2022-05-15.
  32. "Neuroscientist and Stem Cell Biologist Sergiu Pasca to Receive ASCB Early Career Life Scientist Award". ASCB. 2018-10-17. Retrieved 2022-05-15.
  33. Weintraub, Karen (2018-05-24). "Using Medicine and Science to Improve the Quality of Life". The New York Times. ISSN 0362-4331. Retrieved 2022-05-15.
  34. "Sergiu P. Pasca". Vilcek Foundation. Retrieved 2022-05-15.
  35. "American Society for Neurochemistry - Recipients of the Jordi Folch-Pi Award". www.asneurochem.org. Retrieved 2022-05-15.
  36. "Sergiu P. Pasca, M.D." Brain & Behavior Research Foundation. 2017-07-18. Retrieved 2022-05-15.
  37. "Identifying cellular mechanisms of disease and novel therapeutic targets in neurons derived from patients with schizophrenia | MQ Mental Health Research". www.mqmentalhealth.org. 2020-10-28. Retrieved 2022-05-15.
  38. University, © Stanford; Stanford; California 94305 (2017-07-03). "Sammy Kuo Award Winners". Wu Tsai Neurosciences Institute. Retrieved 2022-05-15.
  39. Craciun, Oana (14 January 2013). "EXCLUSIV Sergiu Pașca, studentul român al anului 2012 din străinătate: "Ar fi trebuit să plec la studii mai devreme"". Adevărul (in Romanian). Retrieved 13 March 2016.
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