Lawrence Steinman

Steinman was born in Los Angeles and grew up in Culver City, California. His mother, born in Brooklyn, was the daughter of immigrants from the Pale of Settlement, while his father immigrated from the Zhitomir area in Ukraine around 1921. After World War II, where his father served in combat in the Philippines, his parents settled in Los Angeles, raising their four children near his father's pharmacy, where he worked part-time during high school. Working in the neighborhood pharmacy helped spark his interest in medicine. His sister's battle with poliomyelitis in 1951 influenced his focus on inflammatory brain diseases. He gained early lab experience at the Salk Institute working alongside Jacob Bronowski, Jonas Salk, Seymour Benzer and Stephen Kuffler to research the genetic control of immune responses to viruses.{{cite journal|title=Profile of Lawrence Steinman|date=2016 |pmc=4760808 |last1=Davis |first1=T. |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=113 |issue=6 |pages=1468–1470 |doi=10.1073/pnas.1600083113 |doi-access=free |pmid=26811468 }}

Following the launch of Sputnik, the U.S. invested heavily in science education, providing Steinman with opportunities in math and physics, including a summer program at Oregon State University sponsored by the National Science Foundation.{{cite journal|url=https://www.sciencedirect.com/science/article/pii/S0896627322009163|title=Larry Steinman|journal=Neuron |date=2 November 2022 |volume=110 |issue=21 |pages=3412–3414 |doi=10.1016/j.neuron.2022.10.012 }} He attended Dartmouth College, graduating in Physics, and then pursued his MD at Harvard Medical School. He furthered his training as a post-doctoral fellow in chemical immunology at the Weizmann Institute of Science in Israel.{{cite web|url=https://loop.frontiersin.org/people/39131/bio|title=Brief Bio}}

Steinman joined Stanford University Hospital as a resident in pediatric and adult neurology before joining the faculty in 1980.{{cite web|url=https://health.usnews.com/doctors/lawrence-steinman-590185|title=Dr. Lawrence Steinman MD}} In the biotech industry, he co-founded Neurocrine Biosciences in 1990.{{cite web|url=https://www.metabesity2021.org/lawrence-steinman.html|title=Lawrence Steinman, MD — Co-Chair}} From 2018 to 2022, he chaired the Research Advisory Committee on Gulf War Illness for the US Veteran's Administration. His contributions include chairing the Interdepartmental Program in Immunology at Stanford for 10 years and co-founding companies, including Bayhill Therapeutics (Tolerion),{{cite web|url=https://tolerion.bio/about/|title=About Tolerion}} Nuon Therapeutics, Transparency Life Sciences,{{cite web|url=https://www.biospace.com/b-transparency-life-sciences-b-awarded-1-4-million-ncats-sbir-grant-to-conduct-innovative-trial-of-lisinopril-in-multiple-sclerosis|title=Transparency Life Sciences Awarded $1.4 Million NCATS SBIR Grant To Conduct Innovative Trial Of Lisinopril In Multiple Sclerosis|date=8 September 2014 }} Pasithea Therapeutics, and Atreca.{{cite journal|url=https://www.nature.com/articles/nbt.3226|title=Startups on the menu: Atreca|journal=Nature Biotechnology |date=2015 |volume=33 |issue=5 |page=444 |doi=10.1038/nbt.3226 }} He holds several patents in immunology and therapies that target MS, Huntington's disease, ALS, and Type 1 diabetes.{{cite web|url=http://neurosciencecme.com/cmea_popup_faculty.asp?ID=432|title=Lawrence Steinman, MD}}

Steinman has focused his research on the pathogenesis of multiple sclerosis and related neuroinflammatory diseases, as well as the development of antigen-specific tolerance therapies for autoimmune conditions such as type 1 diabetes and neuromyelitis optica. His laboratory also investigates the role of amyloid structures in diseases like MS, Huntington and Alzheimer.{{cite web|url=https://nrc88.nas.edu/pnas_search/memberDetails.aspx?ctID=14142|title=About the PNAS Member Editor}}

Steinman was a senior author of the 1992 Nature article that identified α4 integrin's crucial role in brain inflammation, emphasizing its role in lymphocyte homing to the MS-affected brain.{{cite journal|url=https://www.nature.com/articles/356063a0|title=Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin|date=1992 |doi=10.1038/356063a0 |last1=Yednock |first1=Ted A. |last2=Cannon |first2=Catherine |last3=Fritz |first3=Lawrence C. |last4=Sanchez-Madrid |first4=Francisco |last5=Steinman |first5=Lawrence |last6=Karin |first6=Nathan |journal=Nature |volume=356 |issue=6364 |pages=63–66 |pmid=1538783 }} Using microarray analysis, he identified distinct transcriptional profiles between acute and chronic MS lesions, pinpointing key inflammatory cytokines and differentially expressed genes.{{cite journal|url=https://www.nature.com/articles/nm0502-500|title=Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis|date=2002 |doi=10.1038/nm0502-500 |last1=Lock |first1=Christopher |last2=Hermans |first2=Guy |last3=Pedotti |first3=Rosetta |last4=Brendolan |first4=Andrea |last5=Schadt |first5=Eric |last6=Garren |first6=Hideki |last7=Langer-Gould |first7=Annette |last8=Strober |first8=Samuel |last9=Cannella |first9=Barbara |last10=Allard |first10=John |last11=Klonowski |first11=Paul |last12=Austin |first12=Angela |last13=Lad |first13=Nagin |last14=Kaminski |first14=Naftali |last15=Galli |first15=Stephen J. |last16=Oksenberg |first16=Jorge R. |last17=Raine |first17=Cedric S. |last18=Heller |first18=Renu |last19=Steinman |first19=Lawrence |journal=Nature Medicine |volume=8 |issue=5 |pages=500–508 }} He continued this analysis of MS brain tissue to identify critical proteins,{{cite journal|url=https://www.annualreviews.org/content/journals/10.1146/annurev-immunol-032713-120227|title=Immunology of Relapse and Remission in Multiple Sclerosis|date=2014 |doi=10.1146/annurev-immunol-032713-120227 |last1=Steinman |first1=Lawrence |journal=Annual Review of Immunology |volume=32 |pages=257–281 |pmid=24438352 }} sugars and lipids{{cite web|url=https://go.gale.com/ps/i.do?id=GALE%7CA185469986&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=00280836&p=AONE&sw=w&userGroupName=anon%7Ed3ec345d&aty=open-web-entry|title=Design of effective immunotherapy for human autoimmunity}}{{cite journal|title=Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation|date=2012 |doi=10.1126/scitranslmed.3003831 |last1=Ho |first1=Peggy P. |last2=Kanter |first2=Jennifer L. |last3=Johnson |first3=Amanda M. |last4=Srinagesh |first4=Hrishikesh K. |last5=Chang |first5=Eun-Ju |last6=Purdy |first6=Timothy M. |last7=Van Haren |first7=Keith |last8=Wikoff |first8=William R. |last9=Kind |first9=Tobias |last10=Khademi |first10=Mohsen |last11=Matloff |first11=Laura Y. |last12=Narayana |first12=Sirisha |last13=Hur |first13=Eun Mi |last14=Lindstrom |first14=Tamsin M. |last15=He |first15=Zhigang |last16=Fiehn |first16=Oliver |last17=Olsson |first17=Tomas |last18=Han |first18=Xianlin |last19=Han |first19=May H. |last20=Steinman |first20=Lawrence |last21=Robinson |first21=William H. |journal=Science Translational Medicine |volume=4 |issue=137 |pages=137ra73 |pmid=22674551 |pmc=3953135 }} involved in acute and chronic pathology in MS brain. These studies on MS brain lesions identified guardian molecules that protect MS brain from injury.{{cite journal|url=https://www.jci.org/articles/view/74255|title=No quiet surrender: molecular guardians in multiple sclerosis brain|date=2015 |doi=10.1172/JCI74255 |last1=Steinman |first1=Lawrence |journal=Journal of Clinical Investigation |volume=125 |issue=4 |pages=1371–1378 |pmid=25831441 |pmc=4396493 }}{{cite journal|url=https://www.nature.com/articles/nri2548|title=A molecular trio in relapse and remission in multiple sclerosis|date=2009 |doi=10.1038/nri2548 |last1=Steinman |first1=Lawrence |journal=Nature Reviews Immunology |volume=9 |issue=6 |pages=440–447 |pmid=19444308 }} Furthermore, he was the global chief investigator on two Phase 3 clinical trials with glycoengineered monoclonal antibodies targeting B cells.{{cite journal|url=https://www.nejm.org/doi/full/10.1056/NEJMoa2201904|title=Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis|date=2022 |doi=10.1056/NEJMoa2201904 |last1=Steinman |first1=Lawrence |last2=Fox |first2=Edward |last3=Hartung |first3=Hans-Peter |last4=Alvarez |first4=Enrique |last5=Qian |first5=Peiqing |last6=Wray |first6=Sibyl |last7=Robertson |first7=Derrick |last8=Huang |first8=Deren |last9=Selmaj |first9=Krzysztof |last10=Wynn |first10=Daniel |last11=Cutter |first11=Gary |last12=Mok |first12=Koby |last13=Hsu |first13=Yanzhi |last14=Xu |first14=Yihuan |last15=Weiss |first15=Michael S. |last16=Bosco |first16=Jenna A. |last17=Power |first17=Sean A. |last18=Lee |first18=Lily |last19=Miskin |first19=Hari P. |last20=Cree |first20=Bruce A.C. |journal=New England Journal of Medicine |volume=387 |issue=8 |pages=704–714 |pmid=36001711 }}

Steinman has conducted various studies on immunology to develop novel therapeutic strategies. While conducting research on the roles of lipids and proteins in MS lesions, he uncovered protective fatty acids and phospholipids, and highlighted αB crystallin as a prevalent transcript with potential as a therapeutic target with guardian properties. His work led to several clinical trials, including an investigation into antigen-specific tolerance for MS, where an engineered DNA plasmid encoding myelin basic protein showed promising results in a phase 2 trial.{{cite journal|url=https://onlinelibrary.wiley.com/doi/full/10.1002/ana.21370|title= Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis|date= 2008|doi= 10.1002/ana.21370|last1= Garren|first1= Hideki|last2= Robinson|first2= William H.|last3= Krasulová|first3= Eva|last4= Havrdová|first4= Eva|last5= Nadj|first5= Congor|last6= Selmaj|first6= Krzysztof|last7= Losy|first7= Jacek|last8= Nadj|first8= Ilinka|last9= Radue|first9= Ernst-Wilhelm|last10= Kidd|first10= Brian A.|last11= Gianettoni|first11= Jill|last12= Tersini|first12= Karen|last13= Utz|first13= Paul J.|last14= Valone|first14= Frank|last15= Steinman|first15= Lawrence|author16= BHT-3009 Study Group|journal= Annals of Neurology|volume= 63|issue= 5|pages= 611–620|pmid= 18481290}} He also demonstrated that T-cell receptors are highly restricted in targeting specific protein segments presented by major histocompatibility complex molecules.{{cite journal|url=https://www.nature.com/articles/345344a0|title=Limited heterogeneity of rearranged T-cell receptor Vα transcripts in brains of multiple sclerosis patients|date=1990 |doi=10.1038/345344a0 |last1=Oksenberg |first1=Jorge R. |last2=Stuart |first2=Simon |last3=Begovich |first3=Ann B. |last4=Bell |first4=Robert B. |last5=Erlich |first5=Henry A. |last6=Steinman |first6=Lawrence |last7=Bernard |first7=Claude C. A. |journal=Nature |volume=345 |issue=6273 |pages=344–346 |pmid=1971424 }}{{cite journal|url=https://www.nature.com/articles/362068a0|title=Selection for T-cell receptor Vβ–Dβ–Jβ gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis|date=1993 |doi=10.1038/362068a0 |last1=Oksenberg |first1=Jorge R. |last2=Panzara |first2=Michael A. |last3=Begovich |first3=Ann B. |last4=Mitchell |first4=Dennis |last5=Erlich |first5=Henry A. |last6=Murray |first6=Ronald S. |last7=Shimonkevitz |first7=Richard |last8=Sherritt |first8=Martina |last9=Rothbard |first9=Jonathan |last10=Bernard |first10=Claude C. A. |last11=Steinman |first11=Lawrence |journal=Nature |volume=362 |issue=6415 |pages=68–70 }}

Steinman's research into the higher prevalence of autoimmune diseases in females revealed the roles of peroxisome proliferator-activated receptors (PPARs) and sex hormones in regulating immune responses.{{cite journal|title=Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific way|date=2012 |doi=10.1073/pnas.1118458109 |last1=Zhang |first1=Monan Angela |last2=Rego |first2=Dorothy |last3=Moshkova |first3=Marina |last4=Kebir |first4=Hania |last5=Chruscinski |first5=Andrzej |last6=Nguyen |first6=Hoangkim |last7=Akkermann |first7=Rainer |last8=Stanczyk |first8=Frank Z. |last9=Prat |first9=Alexandre |last10=Steinman |first10=Lawrence |last11=Dunn |first11=Shannon E. |journal=Proceedings of the National Academy of Sciences |volume=109 |issue=24 |pages=9505–9510 |doi-access=free |pmid=22647601 |pmc=3386070 }} His studies on amyloid fibrils showed that fibrils, such as those derived from β-amyloid and αB crystallin, can suppress inflammation and autoimmune responses.{{cite journal|title=Small Heat Shock Proteins, Amyloid Fibrils, and Nicotine Stimulate a Common Immune Suppressive Pathway with Implications for Future Therapies|date=2019 |pmc=6601455 |last1=Rothbard |first1=J. B. |last2=Kurnellas |first2=M. P. |last3=Ousman |first3=S. S. |last4=Brownell |first4=S. |last5=Rothbard |first5=J. J. |last6=Steinman |first6=L. |journal=Cold Spring Harbor Perspectives in Medicine |volume=9 |issue=7 |pages=a034223 |doi=10.1101/cshperspect.a034223 |pmid=30249602 }}

==Awards and honors==

• 2004 – John Dystel Prize, National Multiple Sclerosis Society
• 2009 – Elected, National Academy of Medicine
• 2011 – Charcot Prize for Lifetime Achievement, International Federation of Multiple Sclerosis Societies
• 2015 – Elected, National Academy of Science
• 2016 – Cerami Prize, Feinstein Institutes for Medical Research
• 2023 – Pioneer in Medicine Award, Society for Brain Mapping & Therapeutics{{cite web|url=https://multiplesclerosisnewstoday.com/lawrence-steinman-honored-research-ties-between-ebv-ms/|title=Lawrence Steinman honored for research on ties between EBV, MS|date=20 February 2023 }}{{cite web|url=https://www.worldbrainmapping.org/lawrence-steinman/|title=Lawrence Steinman|date=6 April 2023 }}

• Yednock, T. A., Cannon, C., Fritz, L. C., Sanchez-Madrid, F., Steinman, L., & Karin, N. (1992). Prevention of experimental autoimmune encephalomyelitis by antibodies against α 4 β l integrin. Nature, 356(6364), 63-66.
• Steinman, L. (2012). The discovery of natalizumab, a potent therapeutic for multiple sclerosis. The Journal of Cell Biology, 199(3), 413. doi: https://doi.org/10.1083/jcb.201207175
• Lock, C., Hermans, G., Pedotti, R., Brendolan, A., Schadt, E., Garren, H., ... & Steinman, L. (2002). Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nature Medicine, 8(5), 500-508.
• Ousman, S. S., Tomooka, B. H., Van Noort, J. M., Wawrousek, E. F., O’Conner, K., Hafler, D. A., ... & Steinman, L. (2007). Protective and therapeutic role for αB-crystallin in autoimmune demyelination. Nature, 448(7152), 474-479.
• Han, M. H., Hwang, S. I., Roy, D. B., Lundgren, D. H., Price, J. V., Ousman, S. S., ... & Steinman, L. (2008). Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature, 451(7182), 1076-1081.
• Ho, P. P., Kanter, J. L., Johnson, A. M., Srinagesh, H. K., Chang, E. J., Purdy, T. M., ... & Robinson, W. H. (2012). Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. Science Translational Medicine, 4(137), 137ra73-137ra73.
• Rothbard, J. B., Kurnellas, M. P., Ousman, S. S., Brownell, S., Rothbard, J. J., & Steinman, L. (2019). Small heat shock proteins, amyloid fibrils, and nicotine stimulate a common immune suppressive pathway with implications for future therapies. Cold Spring Harbor Perspectives in Medicine, 9(7), a034223.
• Steinman, L., Fox, E., Hartung, H. P., Alvarez, E., Qian, P., Wray, S., ... & Cree, B. A. (2022). Ublituximab versus teriflunomide in relapsing multiple sclerosis. New England Journal of Medicine, 387(8), 704-714. doi: 10.1056/NEJMoa2201904.
• Lanz, T. V., Robinson, W. H., Ho, P. P., & Steinman, L. (2023). Roadmap for understanding mechanisms on how Epstein–Barr virus triggers multiple sclerosis and for translating these discoveries in clinical trials. Clinical & Translational Immunology, 12(2), e1438. doi: 10.1002/cti2.1438.
• Chiot, A., Roemer, S. F., Ryner, L., Bogachuk, A., Emberley, K., Brownell, D., ... & Ajami, B. (2023). Elevated α5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target. Proceedings of the National Academy of Sciences, 120(32), e2306731120.

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