User:Marcelosca/sandbox

Marcelosca/sandbox
Born	(1969-03-07) March 7, 1969 Cali, Colombia
Nationality	Colombia
Alma mater	Brown University, Stanford University
Known for	Regulation of gene transcription by calcium signaling, lymphocyte activation, models of human disease using [[induced pluripotent stem cells]], gene therapy
Awards	NIH Director’s Pioneer Award (2008)
Scientific career
Fields	Neurobiology, calcium cell signaling
Institutions	Tempero Bio, Stanford University
Doctoral advisor	Richard Lewis
Other academic advisors	Michael Greenberg

Ricardo Dolmetsch is a Colombian American neuroscientist, Stanford University professor and biotechnology innovator. He is known for his research on calcium signaling in neurons <ref name="MAPK">Dolmetsch RE, Pajvani U, Fife K, Spotts JM, Greenberg ME (Oct 12, 2001). "Signaling to the nucleus by an L- type calcium channel-calmodulin complex through the MAP kinase pathway". Science. 294 (5541): 333–9. doi:10.1126/science.1063395. PMID 11598293. {{cite journal}}: line feed character in |title= at position 34 (help); line feed character in |vauthors= at position 14 (help)</ref> and lymphocytes <ref name="Healy">Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI (April 24, 1997). "Differential activation of transcription factors induced by Ca2+ response amplitude and duration". Nature. 386 (6627): 855–8. doi:10.1038/386855a0. PMID 9126747. {{cite journal}}: line feed character in |pages= at position 5 (help); line feed character in |title= at position 74 (help); line feed character in |vauthors= at position 36 (help)</ref>, and for his work in neuropsychiatric disease <ref name =Miller>Miller, Greg (2014-11-05). "Lab-Grown Neurons Could Help Scientists Repair Damaged Brains, Study Autism". Wired. Retrieved February 17, 2024. {{cite web}}: line feed character in |title= at position 69 (help)</ref><ref name="Dreifus">Dreifus, Claudia (2014-03-24). [https://www.nytimes.com/2014/03/25/science/seeking-autisms-biochemical- roots.html "Seeking Autism's Biochemical Roots"]. The New York Times. Retrieved January 3, 2024. {{cite news}}: Check |url= value (help); line feed character in |title= at position 17 (help); line feed character in |url= at position 72 (help)</ref>. He was an early developer of human stem cell models for studying diseases of the brain<ref name="Miller" /> and heart <ref>Steenhuysen, Julie (2011-02-09). [https://www.reuters.com/article/us-heart-stemcells- idUSTRE7185KF20110209/ "Scientists use stem cells to create heart tissue"]. Reuters. Retrieved February 17, 2024. {{cite web}}: Check |url= value (help); Check date values in: |access-date= (help); line feed character in |access-date= at position 9 (help); line feed character in |title= at position 36 (help); line feed character in |url= at position 52 (help)</ref>, both in his laboratory at Stanford University and at the [[Allen Institute for Brain Science]]. As the Global Head of Neuroscience at Novartis, he developed a neuropsychiatric drug pipeline <ref>Sangamo and Novartis partner on gene therapies for autism. Ben Hargreaves. BioPharma Reporter 03-Aug- 2020</ref><ref>Novartis and Sangamo partner on zinc finger therapies for autism and intellectual disability. Ryan Cross. Chemical and Engineering News, July 30 2020</ref><ref name="Rotman"> Shining Light on Madness. David Rotman, MIT Technology Review. June 17, 2014</ref>, pioneered the use of human stem cell models as tools for drug discovery in neuroscience <ref name="iBiology">"Ricardo Dolmetsch". iBiology. iBiology Inc. Retrieved January 7, 2024.</ref><ref name="Straight talk"> "Straight talk with...Ricardo Dolmetsch". Nat Med. 19: 1360. 2013. doi:[https://doi.org/10.1038%2Fnm1113-%0A1360 10.1038/nm1113- 1360]. {{cite journal}}: Check |doi= value (help); line feed character in |doi= at position 16 (help)</ref> and contributed to the development of several treatments for brain disorders that are now in the clinic including Aimovig (Erenumab) for migraine and Kesimpta (Ofatumumab) for multiple sclerosis. Dolmetsch was also involved in early successes in gene therapy, including two approved therapies - Zolgensma

(a cure for spinal muscular atrophy, sold by Novartis) and Hemgenix (the first gene therapy for hemophilia, made by uniQure and sold by CSL Limited). Dolmetsch is currently the President of Tempero Bio, a biotech company seeking to cure substance use disorders, and an Adjunct Professor in Neurobiology at Stanford University.

Biography and education

Dolmetsch was born and raised in Cali, Colombia and attended Colegio Bolivar. He was a member of the Colombian National Track team, winning the Colombian National Championships and representing his county in both the Pan American and 1986 World Junior Championships in Athletics – Men's long jump. Dolmetsch migrated to the United States to earn a Bachelor in Science from Brown University. He obtained a doctorate in Neuroscience from Stanford University in 1997 under the supervision of Richard Lewis <ref>"People - Alumni". Stanford Medicine. Stanford University. Retrieved January 8, 2024. {{cite web}}: Check date values in: |access-date= (help); line feed character in |access-date= at position 11 (help)</ref>, where he worked on the role of calcium oscillations in lymphocyte activation <ref name="Healy" /><ref>Dolmetsch RE, Xu K, Lewis RS (April 30, 1998). "Calcium oscillations increase the efficiency and specificity of gene expression". Nature. 392 (6679): 933–6. doi:10.1038/31960. PMID 9582075. {{cite journal}}: line feed character in |title= at position 69 (help); line feed character in |vauthors= at position 20 (help)</ref> He completed a postdoctoral fellowship with Michael E. Greenberg at Harvard Medical School where he studied excitation-transcription coupling, specifically the role of voltage-gated calcium channels in controlling the activation of transcription factors in neurons <ref name="MAPK" />. His graduate and postdoctoral work established a role for intracellular calcium oscillation frequency and amplitude in regulating transcription in eukaryotic cells. Dolmetsch was also a co-inventor of the split-enzyme system for detecting protein-protein interactions <ref>Sports JM, Dolmetsch RE, Greenberg ME (Nov 12, 2002). "Time-lapse imaging of a dynamic phosphorylation-dependent protein-protein interaction in mammalian cells". Proc Natl Acad Sci U S A. 99 (23): 15142–7. doi:10.1073/pnas.232565699. PMID 12415118. {{cite journal}}: Check date values in: |date= (help); line feed character in |date= at position 4 (help); line feed character in |title= at position 32 (help); line feed character in |vauthors= at position 11 (help)</ref>

Career

Dolmetsch led a laboratory at Stanford University from 2002-2013 that studied the influence of electrical activity and calcium signals on early brain development <ref name="Poh">Poh, Alyssa (2018-04-08). [https://med.stanford.edu/news/all-news/2008/04/a-young-and-slightly-off-kilter-scientist- thrives.html?microsite=news&tab=news "A young and slightly off- kilter scientist thrives"]. Stanford Medicine. {{cite magazine}}: Check |url= value (help); line feed character in |title= at position 26 (help); line feed character in |url= at position 90 (help)</ref> For two years he was also a Senior Director at the Allen Institute for Brain Science <ref>Herper, Matthew (2012-09-18). [https://www.forbes.com/sites/matthewherper/2012/09/18/inside- paul-allens-quest-to-reverse-engineer-the-brain/?sh=2566575453c6 "Inside Paul Allen's Quest To Reverse Engineer The Brain"]. Forbes. Retrieved 2024- 02-03. {{cite web}}: Check |url= value (help); Check date values in: |access-date= (help); line feed character in |access-date= at position 6 (help); line feed character in |title= at position 12 (help); line feed character in |url= at position 62 (help)</ref><ref>Gewin, V. (2012). "Turning point: Ricardo Dolmetsch". Nature. 485: 537. doi:10.1038/nj7399-537a.</ref>. Early work in the Dolmetsch lab described some of the signaling pathways that connect [[L-type calcium channels]] to gene activation <ref>Gomez-Ospina, N.; Panagiotakos, G.; Portmann, T.; Pasca, S.P.; Rabah, D.; Budzillo, A.; Kinet, J.P.; Dolmetsch, R.E. (2013-04-16). "A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT". PLoS One. 8 (4): e60526. doi:10.1371/journal.pone.0060526. PMID 23613729. {{cite journal}}: line feed character in |title= at position 47 (help)CS1 maint: unflagged free DOI (link)</ref>, and identified the link between voltage gated calcium channels and store-operated calcium channels. <ref>Park, C.Y.; Shcheglovitov, A.; Dolmetsch, R. (2010-10-01). "The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channels". Science. 330 (6000): 101–105. doi:10.1126/science.1191027. PMID 20929812. {{cite journal}}: line feed character in |title= at position 52 (help)</ref> The lab developed technologies to study cell signaling, including light-activated signaling proteins to control biochemical cascades <ref>Yazawa, M.; Sadaghiani, A.M.; Hsueh, B.; Dolmetsch, R.E. (2009-10-04). "Induction of protein-protein interactions in live cells using light". Nat Biotechnol. 27 (10): 941–945. doi:10.1038/nbt.1569. PMID 19801976.</ref>, and induced pluripotent stem cell (iPSC)-based models of cardiac <ref>Yazawa, M.; Hsueh, B.; Jia, X.; Pasca, A. M.; Bernstein, J. A.; Hallmayer, J.; Dolmetsch, R. E. (2011-03-10). "Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome". Nature. 471 (7337): 230–234. doi:10.1038/nature09855. PMID 21307850. {{cite journal}}: line feed character in |title= at position 6 (help)</ref> and neuronal cells. His lab was one of the first to use neurons differentiated from human iPSCs to model neurodevelopmental and neuropsychiatric diseases, both at Stanford and at the [[Allen Institute for Brain Science]]. <ref name="Dreifus" /> His papers on Timothy Syndrome <ref>Paşca, S.P.; Portmann, T.; Voineagu, I.; Yazawa, M.; Shcheglovitov, A.; Paşca, A.M.; Cord, B.; Palmer, T.D.; Chikahisa, S.; Nishino, S.; Bernstein, J.A.; Hallmayer, J.; Geschwind, D.H.; Dolmetsch, R.E. (2011-11-27). "Using iPSC- derived neurons to uncover cellular phenotypes associated with Timothy syndrome". Nat Med. 17 (12): 1657–1662. doi:10.1038/nm.2576. PMID 22120178. {{cite journal}}: line feed character in |title= at position 12 (help)</ref> and Phelan McDermid Syndrome <ref>Shcheglovitov, A.; Shcheglovitova, O.; Yazawa, M.; Portmann, T.; Shu, R.; Sebastiano, V.; Krawisz, A.; Froehlich, W.; Bernstein, J.A.; Hallmayer, J.F.; Dolmetsch, R.E. (2013-11-14). "SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients". Nature. 503 (7475): 267–271. doi:10.1038/nature12618. {{cite journal}}: line feed character in |title= at position 64 (help)|</ref> were among the first to show cellular defects in induced pluripotent stem cells from patients <ref>[https://www.nih.gov/news-events/news-releases/neurons-grown-skin-cells-may- hold-clues-autism "Neurons grown from skin cells may hold clues to autism"]. NIH News Releases. National Institutes of Health. February 17, 2024. {{cite web}}: Check |url= value (help); line feed character in |url= at position 76 (help)</ref><ref name = “Goldman”>Goldman, Bruce (February 17, 2024). [https://stanmed.stanford.edu/brain-tissue-assembloids-expand-brain- understanding/ "Brain tissue 'assembloids' expand brain understanding"]. Stanford Medicine. Stanford University. {{cite web}}: Check |url= value (help); line feed character in |url= at position 68 (help)</ref>, and set the stage for the use of these models for drug development. In 2013, Dolmetsch accepted a position as the Global Head of Neuroscience at the Novartis Institute of Biological Research (NIBR) <ref name="Weintraub">Weintraub, Karen (2013-09-17). [https://www.bostonglobe.com/business/2013/09/17/novartis-cambridge-campus- begins-neuroscience-research/eMmPoRiFEwwh52JCEQtQhJ/story.html?event=event12 "Novartis' Cambridge campus begins neuroscience research"]. The Boston Globe. Retrieved 2024-02-03. {{cite news}}: Check |url= value (help); line feed character in |title= at position 47 (help); line feed character in |url= at position 75 (help)</ref><ref>Weintraub, Karen (2015-12-15). "Academic scientists increasingly turn to industry for research support". STAT News. Retrieved 2024-02-03.</ref><ref name="Dreifus" /><ref name="Straight talk" />. At NIBR, he founded a research and early development team and curated a drug development pipeline that included treatments for rare orphan disorders, neurodegenerative diseases, calcium channelopathies and neuropsychiatric disorders such as autism, schizophrenia and addiction <ref name="Rotman" /> <ref>Branca M (May 2021). "Slivers of the spectrum". Nat Biotechnol. 39 (5). doi:10.1038/s41587-021-00913-8. PMID 33888895.</ref>. His group pioneered the use of human stem cell-derived cellular models <ref>{{cite journal | vauthors = Sun Y, Dolmetsch RE | title = How induced pluripotent stem cells are informing drug discovery in psychiatry | journal = Swiss Med Wkly | volume = 146 | issue = w14241 | date = Jan 11, 2016 | pmid = 26752334 | doi = 10.4414/smw.2016.14241}}</ref> and genome-scale CRISPR screens <ref>{{Cite journal |last1=Ihry |first1=R.J. |last2=Worringer |first2=K.A. |last3=Salick |first3=M.R. |last4=Frias |first4=E. |last5=Ho |first5=D. |last6=Theriault |first6=K. |last7=Kommineni |first7=S. |last8=Chen |first8=J. |last9=Sondey |first9=M. |last10=Ye |first10=C. |last11=Randhawa |first11=R. |last12=Kulkarni |first12=T. |last13=Yang |first13=Z. |last14=McAllister |first14=G. |last15=Russ |first15=C. |last16=Reece-Hoyes |first16=J. |last17=Forrester |first17=W. |last18=Hoffman |first18=G.R. |last19=Dolmetsch |first19=R. |last20=Kaykas |first20=A. |title=p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells |journal=Nat Med |date=July 2018 |volume=24 |issue=7 |pages=939–946 |doi=10.1038/s41591-018-0050-6 |pmid=29892062}}</ref><ref>{{Cite journal |last1=Ihry |first1=R.J. |last2=Salick |first2=M.R. |last3=Ho |first3=D.J. |last4=Sondey |first4=M. |last5=Kommineni |first5=S. |last6=Paula |first6=S. |last7=Raymond |first7=J. |last8=Henry |first8=B. |last9=Frias |first9=E. |last10=Wang |first10=Q. |last11=Worringer |first11=K.A. |last12=Ye |first12=C. |last13=Russ |first13=C. |last14=Reece-Hoyes |first14=J.S. |last15=Altshuler |first15=R.C. |last16=Randhawa |first16=R. |last17=Yang |first17=Z. |last18=McAllister |first18=G.

|last19=Hoffman |first19=G.R. |last20=Dolmetsch |first20=R. |last21=Kaykas |first21=A. |title=Genome-Scale CRISPR Screens Identify Human Pluripotency-Specific Genes |journal=Cell Rep |date=2019-04-09 |volume=27 |issue=2 |pages=616–630.e6 |doi=10.1016/j.celrep.2019.03.043 |pmid=30970262}}</ref> in neuroscience drug development <ref name="iBiology" /> and invested in adeno-associated (AAV) gene therapies <ref>Sabatino DE, Bushman FD, Chandler RJ, Crystal RG, Davidson BL, Dolmetsch R, Eggan KC, Gao G, Gil-Farina I, Kay MA, McCarty DM, Montini E, Ndu A, Yuan J (Aug 3, 2022). "American Society of Gene and Cell Therapy (ASGCT) Working Group on AAV Integration. Evaluating the state of the science for adeno-associated virus integration: An integrated perspective". Mol Ther. 30 (8): 2646–2663. doi:10.1016/j.ymthe.2022.06.004. PMID 35690906. {{cite journal}}: line feed character in |journal= at position 4 (help); line feed character in |title= at position 34 (help); line feed character in |vauthors= at position 38 (help)</ref>. His team at NIBR helped bring several therapies to the clinic, including Erenumab (Aimovig) for migraine, Siponimod (Mayzent) and Ofatumumab (Kesimpta) for multiple sclerosis, and AVX001 (Zolgensma), the first gene therapy for SMA <ref>Stix, Gary (2018-06-06). [https://blogs.scientificamerican.com/talking-back/brain-science-ascends-an- intellectual-mount-everest/ "Brain Science Ascends an Intellectual Mount Everest"]. Scientific American Blog. Retrieved 2024-02-03. {{cite web}}: Check |url= value (help); line feed character in |url= at position 76 (help)</ref><ref> AveXis receives FDA approval for Zolgensma®, the first and only gene therapy for pediatric patients with spinal muscular atrophy (SMA), Novartis Press Release May 14,2019</ref>.

After seven years at Novartis, Dolmetsch was appointed President of Research and Development at uniQure <ref>uniQure Announces Appointment of Ricardo Dolmetsch, Ph.D., as President, Research & Development. Yahoo! Finance August 26, 2020</ref>, a company developing gene therapies for the liver and the central nervous system; he was later promoted to Chief Scientific Officer. Under his leadership uniQure built a broad gene therapy pipeline that included AMT-130, the first gene therapy for Huntington’s disease, AMT260, the first gene therapy for temporal lobe epilepsy, and AMT-191, a treatment for Fabry. He also led uniQure’s successful clinical testing and registration of Hemgenix, a cure for hemophilia that received FDA approval in 2022. Hemgenix received the 2023 Prix Galien USA Award in the category of Rare/Orphan Diseases <ref name = “Prix”>Buntz, Brian (2023-11-01). "Prix Galien Awards: The most innovative biotech, pharma, and orphan drugs of 2023". Drug Discovery and Development. Retrieved January 3, 2024. {{cite web}}: line feed character in |title= at position 12 (help); line feed character in |website= at position 5 (help)</ref>.

Impact and awards

Dolmetsch has published over 70 scientific papers and received numerous awards for his research, including an Andrew Carnegie Prize in Mind and Brain Sciences <ref>[https://www.cmu.edu/news/stories/archives/2014/april/april7_carnegieprizemindbrai

n.html "Press Release: Carnegie Mellon To Present Ricardo Dolmetsch with Andrew Carnegie Prize in Mind and Brain Sciences"]. Carnegie Mellon University. 2014-04-07. Retrieved January 2, 2024. {{cite web}}: Check |url= value (help); line feed character in |publisher= at position 16 (help); line feed character in |title= at position 60 (help); line feed character in |url= at position 82 (help)</ref>, the 2007 Society for Neuroscience Young Investigator Award <ref>[http://agenda- salud.univalle.edu.co/SalaDePrensa/articulos/autismo_3_dic1708_6556.htm "Un caleño revela los secretos del autismo"]. Agenda Salud - Universidad del Valle. 2008-12-17. Retrieved February 17, 2024. {{cite web}}: Check |url= value (help); line feed character in |title= at position 3 (help); line feed character in |url= at position 15 (help); line feed character in |website= at position 15 (help)</ref> <ref>"Breves El Pais". El Tiempo. 2008-01-31. Retrieved February 17, 2024.</ref><ref name="Poh" />, a McKnight Foundation technology award in neuroscience and an NIH Director’s Pioneer Award. While at Stanford he was named a Simons Foundation Autism Research Initiative investigator and a Barbara and John Packard Faculty Scholar. The gene therapy Hemgenix, which he helped shepherd into the clinic at uniQure, was awarded the 2023 Prix Galien Award for Best Product for Rare/Orphan Diseases. <ref name = “Prix”/> Dolmetsch has mentored many scientists that have gone on to successful careers in business and academia including Sergiu P. Pașca <ref name = “Goldman” /><ref>Khan, T.A.; Revah, O.; Gordon, A.; Yoon, S.J.; Krawisz, A.K.; Goold, C.; Sun, Y.; Kim, C.H.; Tian, Y.; Li, M.Y.; Schaepe, J.M.; Ikeda, K.; Amin, N.D.; Sakai, N.; Yazawa, M.; Kushan, L.; Nishino, S.; Porteus, M.H.; Rapoport, J.L.; Bernstein, J.A.; O'Hara, R.; Bearden, C.E.; Hallmayer, J.F.; Huguenard, J.R.; Geschwind, D.H.; Dolmetsch, R.E.; Paşca, S.P. (Dec 2020). "Neuronal defects in a human cellular model of 22q11.2 deletion syndrome". Nat Med. 26 (12): 1888–1898. doi:[https://doi.org/10.1038%2Fs41591-020-%0A1043-9 10.1038/s41591-020- 1043-9]. PMID 32989314. {{cite journal}}: Check |doi= value (help); line feed character in |doi= at position 20 (help); line feed character in |title= at position 9 (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)</ref> Alexander Shcheglovitov, Masayuki Yazawa, Eric Green, Natalia Gomez-Ospina, Ajamete Kaykas, Fiona Elwood <ref>[https://www.pharmavoice.com/news/woman-of-the-week-janssens-fiona- elwood/633362/ "Woman of the Week: Janssen's Fiona Elwood"]. PharmaVoice. Retrieved January 7, 2024. {{cite web}}: Check |url= value (help); line feed character in |url= at position 67 (help)</ref>, Gopi Shankar, Rajeev Sivasankaran and Melvin Evers. He is currently the President of the clinical-stage biotechnology company Tempero Bio that is developing novel medicines to help patients recover from addiction. He is also an Adjunct Professor at Stanford University, where he teaches courses in neurobiology, biotechnology and drug development.