Research Summary

Current Non-NIH Awards:
TR3-05535 Cowan (PI) 11/01/2012-10/31/2015
California Institute of Regenerative Medicine vGene Correction of Autologous Hematopoietic Stem Cells in Artemis Deficient SCID
Goal is to complete the preclinical testing necessary for a clinical gene therapy trial in children with Artemis-SCID. The focus is on optimizing non-chemotherapy approaches to opening marrow niches, studying potential genotoxicity, and demonstrating that gene transduced Artemis deficient hematopoietic stem cells mature in vitro and in vivo into T and B cells.
Role: PI

DR2A-05365 Shizuru (PI) 07/01/2013-06/30/2017
California Institute of Regenerative Medicine vA monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplants
Goal is to bring to a clinical trial a monoclonal antibody that targets hematopoietic stem cells. The antibody will be evaluated in a non-human primate model followed by a prospective phase I/II clinical trial in children with SCID.
Role: Co-PI

I am a pediatric immunologist, Professor of Pediatrics and Chief, Allergy Immunology and BMT Division at UCSF. I led the planning for what ultimately became the Primary Immune Deficiency Treatment Consortium (PIDTC), an NIH-funded group of 43 centers in the US and Canada focused on PID in which I am the PI and UCSF is the lead institution since 2009. I am on the Steering and Executive Committees of the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and established and led for three years the Pediatric Special Interest Group within the American Society of Blood and Marrow Transplantation. My career has focused on children with PID, with over 180 peer-reviewed publications. My major research interests include SCID in Athabascan-speaking Native Americans (SCIDA), gene therapy for children with Artemis-deficient SCID, non-chemotherapy approaches to opening marrow niches, and the use of haploidentical donors and reduced-toxicity transplantation for childhood diseases. I performed one of the initial haplocompatible T cell depleted marrow transplants for SCID in North America in 1982 and reported one of the first in utero transplants in the world, the first patient with multiple biotin-dependent carboxylase deficiencies and immune deficiency, and the first children with HIV infection. I have treated the largest cohort of children with SCIDA and the largest number of babies diagnosed through newborn screening with SCID in North America, mapped the genetic locus of the gene for SCIDA and radiation sensitive SCID (RS-SCID), and identified the mutation in DCLRE1C responsible for SCIDA in Navajo and Apache children. I designed and completed one of the few prospective single institution trials of haplocompatible HCT for children with SCID and initiated and completed the first large study of children with SCID transplanted in North America and reported by the PIDTC.

Research Funding

  • September 12, 2009 - August 31, 2024 - Primary Immune Deficiency Treatment Consortium , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U54AI082973
  • May 1, 2018 - April 30, 2023 - Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency Using a Lentiviral Vector to Transduce Autologous CD34 Hematopoietic Stem Cells , Principle Investigator . Sponsor: California Institute of Regenerative Medicine, Sponsor Award ID: CLIN2-10830
  • April 1, 2017 - March 31, 2022 - Lentiviral Gene Therapy for Infants with X-linked Severe Combined Immunodeficiency using Autologous Bone Marrow Stem Cells and Busulfan Conditioning , Co-PI . Sponsor: California Institute of Regenerative Medicine, Sponsor Award ID: CLIN2-09504
  • March 2, 2011 - February 28, 2021 - Annual Primary Immune Deficiency Treatment Consortium (PIDTC) Workshop and Education Day , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13AI094943


Massachusetts Institute of Technology, Cambridge, MA, B.S., 1966, Electrical Engineering
University of Pennsylvania, Philadelphia, PA, M.D., 1970, Medicine
University of California, San Francisco, Intern/Resident, 1975-77, Pediatrics
University of California, San Francisco, Fellow, 1977-79, Immunology

Honors & Awards

  • 1966
    Tau Beta Pi, Engineer Honor Society
  • 1968-70
    Charles Hovies Scholarship
  • 1979-82
    Pediatric Clinical Research Center Investigator Award

Selected Publications

  1. Yan KK, Condori J, Ma Z, Metais JY, Ju B, Ding L, Dhungana Y, Palmer LE, Langfitt DM, Ferrara F, Throm R, Shi H, Risch I, Bhatara S, Shaner B, Lockey TD, Talleur AC, Easton J, Meagher MM, Puck JM, Cowan MJ, Zhou S, Mamcarz E, Gottschalk S, Yu J. Integrome signatures of lentiviral gene therapy for SCID-X1 patients. Sci Adv. 2023 Oct 06; 9(40):eadg9959.  View on PubMed
  2. Eissa H, Thakar M, Shah AJ, Logan B, Griffith LM, Dong H, Parrott RE, O'Reilly R, Dara J, Kapoor N, Satter LF, Chandra S, Kapadia M, Chandrakasan S, Knutsen A, Jyonouchi SC, Molinari L, Rayes A, Ebens CL, Teira P, Dávila Saldaña BJ, Burroughs LM, Chaudhury S, Chellapandian D, Gillio AP, Goldman F, Malech HL, DeSantes K, Cuvelier GDE, Rozmus J, Quinones R, Yu LC, Broglie L, Aquino V, Shereck E, Moore TB, Lugt MV, Mousallem TI, Oved JH, Dorsey M, Azim HA, Martinez C, Bleesing J, Prockop S, Kohn DB, Bednarski JJ, Leiding J, Marsh RA, Torgerson T, Notarangelo LD, Pai SY, Pulsipher MA, Puck JM, Dvorak CC, Haddad E, Buckley RH, Cowan MJ, Heimall J. Post-Transplant Late Complications Increase Over Time for Patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) Landmark Study. J Allergy Clin Immunol. 2023 Oct 02.  View on PubMed
  3. Chandrasekaran P, Han Y, Zerbe CS, Heller T, DeRavin SS, Kreuzberg SA, Marciano BE, Siu Y, Jones DR, Abraham RS, Stephens MC, Tsou AM, Snapper S, Conlan S, Subramanian P, Quinones M, Grou C, Calderon V, Deming C, Leiding JW, Arnold DE, Logan BR, Griffith LM, Petrovic A, Mousallem TI, Kapoor N, Heimall JR, Barnum JL, Kapadia M, Wright N, Rayes A, Chandra S, Broglie LA, Chellapandian D, Deal CL, Grunebaum E, Lim SS, Mallhi K, Marsh RA, Murguia-Favela L, Parikh S, Touzot F, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo L, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Kang EM, Malech HL, Segre JA, Bryant CE, Holland SM, Falcone EL. Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease. J Allergy Clin Immunol. 2023 Aug 31.  View on PubMed
  4. Leiding JW, Arnold DE, Parikh SH, Logan BR, Marsh RA, Griffith LM, Wu R, Kidd S, Mallhi KK, Chellapandian D, Si Lim S, Grunebaum E, Falcone EL, Murguia-Favela L, Grossman D, Prasad VK, Heimall JR, Touzot F, Burroughs L, Bleesing J, Kapoor N, Dara J, Williams O, Kapadia M, Oshrine BR, Bednarski JJ, Rayes A, Chong H, Cuvelier GDE, Forbes Satter LR, Martinez C, Vander Lugt MT, Yu LC, Chandrakasan S, Joshi A, Prockop SE, Dávila Saldaña BJ, Aquino V, Broglie L, Ebens CL, Madden LM, DeSantes K, Milner J, Rangarajan HG, Shah A, Gilio AP, Knutsen AP, Miller HK, Moore TB, Graham P, Bauchat A, Bunin NJ, Teira P, Petrovic A, Chandra S, Abdel-Azim H, Dorsey M, Birbrayer O, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Malech HL, Kang EM. Genotype, Oxidase Status, and Preceding Infection or Autoinflammation Do Not Affect Allogeneic HCT Outcomes for CGD. Blood. 2023 Aug 10.  View on PubMed
  5. Thakar MS, Logan BR, Puck JM, Dunn EA, Buckley RH, Cowan MJ, O'Reilly RJ, Kapoor N, Satter LF, Pai SY, Heimall J, Chandra S, Ebens CL, Chellapandian D, Williams O, Burroughs LM, Saldana BD, Rayes A, Madden LM, Chandrakasan S, Bednarski JJ, DeSantes KB, Cuvelier GDE, Teira P, Gillio AP, Eissa H, Knutsen AP, Goldman FD, Aquino VM, Shereck EB, Moore TB, Caywood EH, Lugt MTV, Rozmus J, Broglie L, Yu LC, Shah AJ, Andolina JR, Liu X, Parrott RE, Dara J, Prockop S, Martinez CA, Kapadia M, Jyonouchi SC, Sullivan KE, Bleesing JJ, Chaudhury S, Petrovic A, Keller MD, Quigg TC, Parikh S, Shenoy S, Seroogy C, Rubin T, Decaluwe H, Routes JM, Torgerson TR, Leiding JW, Pulsipher MA, Kohn DB, Griffith LM, Haddad E, Dvorak CC, Notarangelo LD. Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium. Lancet. 2023 07 08; 402(10396):129-140.  View on PubMed
  6. Schuetz C, Gerke J, Ege M, Walter J, Kusters M, Worth A, Kanakry JA, Dimitrova D, Wolska-Kusnierz B, Chen K, Unal E, Karakukcu M, Pashchenko O, Leiding J, Kawai T, Amrolia PJ, Berghuis D, Buechner J, Buchbinder D, Cowan MJ, Gennery AR, Güngör T, Heimall J, Miano M, Meyts I, Morris EC, Rivière J, Sharapova SO, Shaw PJ, Slatter M, Honig M, Veys P, Fischer A, Cavazzana M, Moshous D, Schulz A, Albert MH, Puck JM, Lankester AC, Notarangelo LD, Neven B. Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT. Blood. 2023 02 16; 141(7):713-724.  View on PubMed
  7. Tomomasa D, Isoda T, Mitsuiki N, Inoue K, Nishimura A, Uda K, Uchiyama T, Yamashita M, Kamiya T, Endo A, Takagi M, Imai K, Kajiwara M, Cowan MJ, Morio T, Kanegane H. Successful TCRαβ/CD19-Depleted Hematopoietic Cell Transplantation for a Patient With Artemis Deficiency. J Pediatr Hematol Oncol. 2023 03 01; 45(2):e285-e289.  View on PubMed
  8. Cowan MJ, Yu J, Facchino J, Fraser-Browne C, Sanford U, Kawahara M, Dara J, Long-Boyle J, Oh J, Chan W, Chag S, Broderick L, Chellapandian D, Decaluwe H, Golski C, Hu D, Kuo CY, Miller HK, Petrovic A, Currier R, Hilton JF, Punwani D, Dvorak CC, Malech HL, McIvor RS, Puck JM. Lentiviral Gene Therapy for Artemis-Deficient SCID. N Engl J Med. 2022 12 22; 387(25):2344-2355.  View on PubMed
  9. Forlanini F, Chan A, Dara J, Dvorak CC, Cowan MJ, Puck JM, Dorsey MJ. Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders. J Clin Immunol. 2023 04; 43(3):636-646.  View on PubMed
  10. Dvorak CC, Haddad E, Heimall J, Dunn E, Buckley RH, Kohn DB, Cowan MJ, Pai SY, Griffith LM, Cuvelier GDE, Eissa H, Shah AJ, O'Reilly RJ, Pulsipher MA, Wright NAM, Abraham RS, Satter LF, Notarangelo LD, Puck JM. The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions. J Allergy Clin Immunol. 2023 02; 151(2):539-546.  View on PubMed
  11. Dvorak CC, Haddad E, Heimall J, Dunn E, Cowan MJ, Pai SY, Kapoor N, Satter LF, Buckley RH, O'Reilly RJ, Chandra S, Bednarski JJ, Williams O, Rayes A, Moore TB, Ebens CL, Davila Saldana BJ, Petrovic A, Chellapandian D, Cuvelier GDE, Vander Lugt MT, Caywood EH, Chandrakasan S, Eissa H, Goldman FD, Shereck E, Aquino VM, Desantes KB, Madden LM, Miller HK, Yu L, Broglie L, Gillio A, Shah AJ, Knutsen AP, Andolina JP, Joshi AY, Szabolcs P, Kapadia M, Martinez CA, Parrot RE, Sullivan KE, Prockop SE, Abraham RS, Thakar MS, Leiding JW, Kohn DB, Pulsipher MA, Griffith LM, Notarangelo LD, Puck JM. The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions. J Allergy Clin Immunol. 2023 02; 151(2):547-555.e5.  View on PubMed
  12. Inoue K, Miyamoto S, Tomomasa D, Adachi E, Azumi S, Horikoshi Y, Ishihara T, Osone S, Kawahara Y, Kudo K, Kato Z, Ohnishi H, Kashimada K, Imai K, Ohara O, van Zelm MC, Cowan MJ, Morio T, Kanegane H. Clinical and Genetic Characterization of Patients with Artemis Deficiency in Japan. J Clin Immunol. 2023 Apr; 43(3):585-594.  View on PubMed
  13. Cuvelier GDE, Logan BR, Prockop SE, Buckley RH, Kuo CY, Griffith LM, Liu X, Yip A, Hershfield MS, Ayoub PG, Moore TB, Dorsey MJ, O'Reilly RJ, Kapoor N, Pai SY, Kapadia M, Ebens CL, Forbes Satter LR, Burroughs LM, Petrovic A, Chellapandian D, Heimall J, Shyr DC, Rayes A, Bednarski JJ, Chandra S, Chandrakasan S, Gillio AP, Madden L, Quigg TC, Caywood EH, Dávila Saldaña BJ, DeSantes K, Eissa H, Goldman FD, Rozmus J, Shah AJ, Vander Lugt MT, Thakar MS, Parrott RE, Martinez C, Leiding JW, Torgerson TR, Pulsipher MA, Notarangelo LD, Cowan MJ, Dvorak CC, Haddad E, Puck JM, Kohn DB. Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC. Blood. 2022 08 18; 140(7):685-705.  View on PubMed
  14. Labrosse R, Boufaied I, Bourdin B, Gona S, Randolph HE, Logan BR, Bourbonnais S, Berthe C, Chan W, Buckley RH, Parrott RE, Cuvelier GDE, Kapoor N, Chandra S, Dávila Saldaña BJ, Eissa H, Goldman FD, Heimall J, O'Reilly R, Chaudhury S, Kolb EA, Shenoy S, Griffith LM, Pulsipher M, Kohn DB, Notarangelo LD, Pai SY, Cowan MJ, Dvorak CC, Haddad É, Puck JM, Barreiro LB, Decaluwe H. Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation. J Allergy Clin Immunol. 2023 01; 151(1):260-271.  View on PubMed
  15. De Ravin SS, Liu S, Sweeney CL, Brault J, Whiting-Theobald N, Ma M, Liu T, Choi U, Lee J, O'Brien SA, Quackenbush P, Estwick T, Karra A, Docking E, Kwatemaa N, Guo S, Su L, Sun Z, Zhou S, Puck J, Cowan MJ, Notarangelo LD, Kang E, Malech HL, Wu X. Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency. Nat Commun. 2022 06 28; 13(1):3710.  View on PubMed
  16. Arnold DE, Chellapandian D, Parikh S, Mallhi K, Marsh RA, Heimall JR, Grossman D, Chitty-Lopez M, Murguia-Favela L, Gennery AR, Boulad F, Arbuckle E, Cowan MJ, Dvorak CC, Griffith LM, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson T, Kang EM, Malech HL, Leiding JW. Granulocyte Transfusions in Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Cell Transplantation or Gene Therapy. J Clin Immunol. 2022 07; 42(5):1026-1035.  View on PubMed
  17. Bognàr T, Bartelink IH, Egberts TCG, Rademaker CMA, Versluys AB, Slatter MA, Kletzel M, Nath CE, Cuvelier GDE, Savic RM, Dvorak C, Long-Boyle JR, Cowan MJ, Bittencourt H, Bredius RGM, Güngör T, Shaw PJ, Ansari M, Hassan M, Krajinovic M, Hempel G, Marktel S, Chiesa R, Théoret Y, Lund T, Orchard PJ, Wynn RF, Boelens JJ, Lalmohamed A. Association Between the Magnitude of Intravenous Busulfan Exposure and Development of Hepatic Veno-Occlusive Disease in Children and Young Adults Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation. Transplant Cell Ther. 2022 04; 28(4):196-202.  View on PubMed
  18. Kovac V, Shapiro EG, Rudser KD, Mueller BA, Eisengart JB, Delaney KA, Ahmed A, King KE, Yund BD, Cowan MJ, Raiman J, Mamak EG, Harmatz PR, Shankar SP, Ali N, Cagle SR, Wozniak JR, Lim KO, Orchard PJ, Whitley CB, Nestrasil I. Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I. Mol Genet Metab. 2022 02; 135(2):122-132.  View on PubMed
  19. Delmonte OM, Castagnoli R, Yu J, Dvorak CC, Cowan MJ, Dávila Saldaña BJ, De Ravin SS, Mamcarz E, Chang CK, Daley SR, Griffith LM, Notarangelo LD, Puck JM. Poor T-cell receptor β repertoire diversity early posttransplant for severe combined immunodeficiency predicts failure of immune reconstitution. J Allergy Clin Immunol. 2022 03; 149(3):1113-1119.  View on PubMed
  20. Smith H, Scalchunes C, Cowan MJ, Puck J, Heimall J. Expectations and experience: Parent and patient perspectives regarding treatment for Severe Combined Immunodeficiency (SCID). Clin Immunol. 2021 08; 229:108778.  View on PubMed

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