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Katherine A. High

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Katherine A. High
BERJAYA
High in 2026
Born
High Point, North Carolina
Alma materHarvard College, University of North Carolina School of Medicine
Known forGene Therapy
Childrenthree, including Sarah Steele
Scientific career
FieldsHematology
InstitutionsUniversity of Pennsylvania, Spark Therapeutics
Academic advisors
Edward J. Benz Jr.

Katherine A. High is an American physician-scientist who is an emeritus professor at the Perelman School of Medicine at the University of Pennsylvania. She was the co-founder, president, and chief scientific officer of Spark Therapeutics and currently serves as CEO of the ophthalmology gene therapy company RhyGaze.[1][2] She has been recognized for her contributions to the field of gene therapy, having designed, sponsored, and conducted the first clinical trial of an adeno-associated viral vector (AAV) gene therapy injected into the skeletal muscle (1999),[3] the first trial of AAV gene therapy introduced into the liver (2001),[4] and the first trial in the US of an AAV gene therapy injected into the subretinal space (2007).[5] She was among the first to elucidate human immune responses to systemically administered AAV vectors, and developed solutions that are used in clinical gene therapy.[6][7][8][9] High is an elected member of the National Academy of Medicine,[10] the National Academy of Sciences,[11] the American Academy of Arts and Sciences,[12] and the Royal College of Physicians.[13]

Education

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High received an A.B. in chemistry at Harvard University in 1972.[14][15] She started her medical training at the University of North Carolina (UNC) School of Medicine, during which she took a leave of absence to work in a chemistry research lab at UNC.[16] After returning and completing her medical degree in 1978, High continued with a residency in internal medicine.[17] She then became a hematology fellow at Yale University under the supervision of Edward J Benz Jr, during which she worked on the molecular genetics of globin genes and oncogenes.[18][17]

Career and research

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Research on hemophilia gene therapy

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High was a faculty member at the University of North Carolina - Chapel Hill for seven years,[19][17] where she started her career by cloning the normal canine Factor IX gene and then characterizing the mutation in a naturally occurring canine model of hemophilia B, to enable gene therapy studies for the disease in a canine model.[20] She also identified several mutations responsible for human hemophilia B,[21][22] as well as Factor VII,[23][24] and Factor X[25][26]-deficient blood clotting disorders.[27] High moved to the University of Pennsylvania and Children's Hospital of Philadelphia, where she began pioneering clinical trials of gene therapy for blood disorders.[28] During her career at the University of Pennsylvania, High expanded her research into gene therapy solutions for hereditary blindness together with Dr. Jean Bennett.[29]

She was the director of the Center for Cellular and Molecular Therapeutics, and beginning in 2001, head of hematology research,[2] at the Children's Hospital of Philadelphia, where she was also an investigator of the Howard Hughes Medical Institute.[30][31]

Spark Therapeutics

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From 2014 to 2020, High served as the co-founder, President, Chief Scientific Officer/Head of R&D and a Member of the Board of Directors of Spark Therapeutics, a fully integrated, commercial gene therapy company in Philadelphia. While at Spark Therapeutics, Dr. High led the team that obtained the first FDA approval of an AAV therapeutic (Voretigene neparvovec for the treatment of an inherited disorder causing blindness) in December 2017 and led the teams that obtained Breakthrough Therapy designation and FDA approval for Fidanacogene elaparvovec to treat Hemophilia B and Breakthrough Therapy designation for Dirloctogene samoparvovec to treat Hemophilia A.

Spark Therapeutics was bought by Swiss pharma company Roche in December 2019 for $4.3 billion. In February 2020, High stepped down from her position at the company.[32]

Post-Spark Therapeutics

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In January 2021, High joined Asklepios Biopharmaceutical, or AskBio, a clinical-stage adeno-associated virus (AAV) gene therapy company and wholly owned subsidiary of Bayer AG, as the company's new President of Therapeutics and as a board member for AskBio. In 2024 she became Chief Executive Officer of the genetic medicine company RhyGaze.[33]

Other activities

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Dr. High has served on NIH study sections for hematology and for therapeutic approaches to genetic disease.[34] She served on the National Heart, Lung and Blood Advisory Council,[34] on the NIH Clinical Center Advisory Council, and on the Board of Scientific Counsellors for the National Eye Institute. She served a 4 year term on the FDA Advisory Committee on Cell, Tissue and Gene Therapy (2001–2005)[35] and served as the President of the American Society of Gene and Cell Therapy (2004–2005).[35]

Awards

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  • 2000 – National Bleeding Disorders Foundation, Researcher of the Year award[36]
  • 2009 – Foundation Fighting Blindness, Board of Directors Award[37]
  • 2010 – American Society of Gene and Cell Therapy, Outstanding Achievement Award[38]
  • 2014 – Human Gene Therapy, Pioneer Award[39]
  • 2018 – Sanford Health's $1 million Lorraine Cross Award for innovation in medicine and science, shared with Jean Bennett[40]
  • 2022 – American Society of Gene and Cell Therapy, Jerry Mendell Award for Translational Science[41]
  • 2022 – Children's Hospital of Philadelphia, Gold Medal for transformative impact on children's health through gene therapy[42]
  • 2026 – Breakthrough Prize in Life Sciences[43]

Personal life

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High is married to George Steele, an internist who was on the faculty of the University of Pennsylvania School of Medicine.[44][45] She has three children, one of whom is actress Sarah Steele.[46][47]

References

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  1. ^ "Spark co-founder Katherine High leads RhyGaze – Bizwomen". Pacific Business News. Retrieved 2026-04-17.
  2. ^ a b Yarbrough, Cathy (3 September 2018). "Gene Therapy Pioneer's 30 Years Of Problem-Solving". Life Science Leader.
  3. ^ Kay MA, Manno CS, Ragni MV, Larson PJ, Couto LB, McClelland A, Glader B, Chew AJ, Tai SJ, Herzog RW, Arruda V, Johnson F, Scallan C, Skarsgard E, Flake AW, High KA (2000). "Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector". Nature Genetics. 24 (3): 257–261. doi:10.1038/73464. PMID 10700178. S2CID 12650196.
  4. ^ Manno CS, Arruda VR, Pierce GF, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt, P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA (2006). "Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response". Nature Medicine. 12 (3): 342–347. doi:10.1038/nm1358. PMID 16474400. S2CID 14664182.
  5. ^ Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (April 28, 2008). "Safety and efficacy of gene transfer for Leber's Congenital Amaurosis". New England Journal of Medicine. 358 (21): 2240–2248. doi:10.1056/NEJMoa0802315. PMC 2829748. PMID 18441370.
  6. ^ "Human Immune Responses to AAV-2 Capsid May Limit Duration of Expression in Liver-Directed Gene Transfer in Humans with Hemophilia B." ashpublications.
  7. ^ Manno, Catherine S.; Pierce, Glenn F.; Arruda, Valder R.; Glader, Bertil; Ragni, Margaret; Rasko, John J.; Ozelo, Margareth C.; Hoots, Keith; Blatt, Philip; Konkle, Barbara; Dake, Michael; Kaye, Robin; Razavi, Mahmood; Zajko, Albert; Zehnder, James (2006-03-01). "Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response". Nature Medicine. 12 (3): 342–347. doi:10.1038/nm1358. ISSN 1078-8956. PMID 16474400.
  8. ^ Mingozzi, Federico; High, Katherine A. (2011-08-01). "Immune responses to AAV in clinical trials". Current Gene Therapy. 11 (4): 321–330. doi:10.2174/156652311796150354. ISSN 1875-5631. PMID 21557723.
  9. ^ Mingozzi, Federico; High, Katherine A. (2013-07-04). "Immune responses to AAV vectors: overcoming barriers to successful gene therapy". Blood. 122 (1): 23–36. doi:10.1182/blood-2013-01-306647. ISSN 1528-0020. PMC 3701904. PMID 23596044.
  10. ^ "Katherine Ann High - NAM". nam.edu. Retrieved 2026-04-17.
  11. ^ "Katherine Ann High – NAS". nasonline. Retrieved 2026-04-17.
  12. ^ "Katherine Ann High | American Academy of Arts and Sciences". www.amacad.org. 2026-03-18. Retrieved 2026-04-17.
  13. ^ Philadelphia, The Children's Hospital of. "Children's Hospital of Philadelphia Awards Gold Medal to Dr. Katherine High, Gene Therapy Pioneer | Children's Hospital of Philadelphia". www.chop.edu. Retrieved 2026-04-17.
  14. ^ "Katherine A. High | Faculty | About Us | Perelman School of Medicine | Perelman School of Medicine at the University of Pennsylvania". med.upenn.edu. Retrieved 6 November 2019.
  15. ^ "Katherine High, M.D. | Board Member". Spark Therapeutics Inc. – IR Site. Archived from the original on 23 December 2019. Retrieved 6 November 2019.
  16. ^ Wilson, James M. (1 December 2016). "Interview with Katherine A. High, MD". Human Gene Therapy Clinical Development. 27 (4): 127–131. doi:10.1089/humc.2016.29021.int. ISSN 2324-8637. PMID 27983889.
  17. ^ a b c "Katherine A. High, MD". IHG Symposium 2015. 1 September 2015. Archived from the original on 14 September 2018. Retrieved 6 November 2019.
  18. ^ Wilson, James M. (December 2016). "Interview with Katherine A. High, MD". Human Gene Therapy Clinical Development. 27 (4): 127–131. doi:10.1089/humc.2016.29021.int. ISSN 2324-8637. PMID 27983889.
  19. ^ "Factor This! Series: An Interview with Dr. Katherine A. High ·". onthepulseconsultancy.com. 19 January 2018. Retrieved 6 November 2019.
  20. ^ Evans, J. P.; Watzke, H. H.; Ware, J. L.; Stafford, D. W.; High, K. A. (July 1989). "Molecular cloning of a cDNA encoding canine factor IX". Blood. 74 (1): 207–212. doi:10.1182/blood.V74.1.207.207. ISSN 0006-4971. PMID 2752110.
  21. ^ Monroe, D. M.; McCord, D. M.; Huang, M. N.; High, K. A.; Lundblad, R. L.; Kasper, C. K.; Roberts, H. R. (1989-05-01). "Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo". Blood. 73 (6): 1540–1544. ISSN 0006-4971. PMID 2713493.
  22. ^ Lozier, J. N.; Monroe, D. M.; Stanfield-Oakley, S.; Lin, S. W.; Smith, K. J.; Roberts, H. R.; High, K. A. (1990-03-01). "Factor IX New London: substitution of proline for glutamine at position 50 causes severe hemophilia B". Blood. 75 (5): 1097–1104. ISSN 0006-4971. PMID 2306516.
  23. ^ Chaing, S.; Clarke, B.; Sridhara, S.; Chu, K.; Friedman, P.; VanDusen, W.; Roberts, H. R.; Blajchman, M.; Monroe, D. M.; High, K. A. (1994-06-15). "Severe factor VII deficiency caused by mutations abolishing the cleavage site for activation and altering binding to tissue factor". Blood. 83 (12): 3524–3535. ISSN 0006-4971. PMID 8204879.
  24. ^ Arbini, A. A.; Pollak, E. S.; Bayleran, J. K.; High, K. A.; Bauer, K. A. (1997-01-01). "Severe factor VII deficiency due to a mutation disrupting a hepatocyte nuclear factor 4 binding site in the factor VII promoter". Blood. 89 (1): 176–182. ISSN 0006-4971. PMID 8978290.
  25. ^ Watzke, H. H.; Wallmark, A.; Hamaguchi, N.; Giardina, P.; Stafford, D. W.; High, K. A. (1991-11-01). "Factor XSanto Domingo. Evidence that the severe clinical phenotype arises from a mutation blocking secretion". The Journal of Clinical Investigation. 88 (5): 1685–1689. doi:10.1172/JCI115484. ISSN 0021-9738. PMC 295703. PMID 1939653.
  26. ^ Racchi, M.; Watzke, H. H.; High, K. A.; Lively, M. O. (1993-03-15). "Human coagulation factor X deficiency caused by a mutant signal peptide that blocks cleavage by signal peptidase but not targeting and translocation to the endoplasmic reticulum". The Journal of Biological Chemistry. 268 (8): 5735–5740. ISSN 0021-9258. PMID 8449937.
  27. ^ Chaing, S.; Clarke, B.; Sridhara, S.; Chu, K.; Friedman, P.; VanDusen, W.; Roberts, H. R.; Blajchman, M.; Monroe, D. M.; High, K. A. (1994-06-15). "Severe factor VII deficiency caused by mutations abolishing the cleavage site for activation and altering binding to tissue factor". Blood. 83 (12): 3524–3535. doi:10.1182/blood.V83.12.3524.3524. ISSN 0006-4971. PMID 8204879.
  28. ^ Herzog, R. W.; Yang, E. Y.; Couto, L. B.; Hagstrom, J. N.; Elwell, D.; Fields, P. A.; Burton, M.; Bellinger, D. A.; Read, M. S.; Brinkhous, K. M.; Podsakoff, G. M. (January 1999). "Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector". Nature Medicine. 5 (1): 56–63. doi:10.1038/4743. ISSN 1078-8956. PMID 9883840. S2CID 21832836.
  29. ^ "Dr. Jean Bennett & Dr. Katherine High Win $1 Million Sanford Lorraine Cross Award". Smithsonian. Retrieved 6 November 2019.
  30. ^ "Katherine High" (PDF). Retrieved 1 October 2017.[permanent dead link]
  31. ^ "Katherine A. High, MD – IHG Symposium 2015". IHG Symposium 2015. 1 September 2015. Archived from the original on 14 September 2018. Retrieved 1 October 2017.
  32. ^ "Spark Co-Founder Katherine High Departs Company Ahead of Merger with Roche". BioSpace. Retrieved 25 February 2020.
  33. ^ "RhyGaze". RhyGaze. Retrieved 2026-04-17.
  34. ^ a b "Katherine High, M.D." National Heart, Lung, and Blood Institute (NHLBI). Retrieved 2024-05-22.
  35. ^ a b "Katherine High". Gairdner Foundation. Retrieved 2024-05-22.
  36. ^ "Historical Awards of Excellence Winners". National Bleeding Disorders Foundation. Retrieved 2024-05-22.
  37. ^ "Katherine High". Gairdner Foundation. Retrieved 2024-05-22.
  38. ^ "Outstanding Achievement Award". American Society of Gene and Cell Therapy. Retrieved 2024-05-22.
  39. ^ "Pioneer Award". EurekAlert!. Retrieved 2024-05-22.
  40. ^ "Sanford Health awards $1 million Lorraine Cross Award". Sanford Health. Retrieved 2024-05-22.
  41. ^ "Dr. Katherine High Receives Award from American Society of Gene and Cell Therapy". AskBio. Retrieved 2024-05-22.
  42. ^ "Children's Hospital of Philadelphia Awards Gold Medal to Dr. Katherine High". Children's Hospital of Philadelphia. Retrieved 2024-05-22.
  43. ^ Breakthrough Prize in Life Sciences 2026
  44. ^ "Growing into her biggest film role". Los Angeles Times. 26 December 2004. Retrieved 17 July 2020.
  45. ^ Elkin, Michael (26 July 2013). "Sarah Steele finding herself on everybody's to-hire list". inquirer.com. Retrieved 17 July 2020.
  46. ^ admin (30 May 2018). "Pulling Back the Curtain: Katherine A. High, MD". ASH Clinical News. Retrieved 17 July 2020.
  47. ^ Healy, Patrick (28 June 2012). "Role After Role, She Cuts Years Off Her Age". The New York Times. ISSN 0362-4331. Retrieved 17 July 2020.
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