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

Overview:
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
  • March 1, 1982 - May 31, 2015 - Bio-Organic Biomedical Mass Spectrometry Resource , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41RR001614
  • June 1, 1975 - April 30, 2015 - California National Primate Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P51RR000169
  • December 1, 1974 - March 31, 2009 - General Clinical Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: M01RR000079
  • December 1, 1981 - March 31, 2007 - PEDIATRIC CLINICAL RESEARCH CENTER , Co-Investigator . Sponsor: NIH, Sponsor Award ID: M01RR001271
  • January 1, 1998 - March 31, 2006 - Tolerance post in utero transplantation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL058842
  • September 30, 1993 - June 30, 2003 - GENE LINKAGE STUDY OF IMMUNODEFICIENCY IN NAVAJO INDIANS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI028339
  • August 1, 1990 - July 31, 1995 - INDUCTION OF TOLERANCE IN MARROW TRANSPLANTATION , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P01AI029512
  • September 30, 1986 - March 31, 1993 - HIV INFECTION IN CHILDREN OF IV DRUG ABUSING WOMEN , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DA004331

Education

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. Jacovas VC, Zelnick M, McNulty S, Ross JE, Khurana N, Pan X, Nieto A, Martin S, McLean B, Elnagheeb MA, Cowan MJ, Puck JM, Hershfield M, Verbsky J, Walter J, Allenspach E, Chan AY, van Oers NSC, Ghosh R, Piazza M, Yuan B, Notarangelo LD, Johnson BA, Chinn IK. The ClinGen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications for classification of variants in ADA , DCLRE1C , IL2RG , IL7R , JAK3 , RAG1 , and RAG2. medRxiv. 2025 Feb 13.  View on PubMed
  2. Dvorak CC, Temple WC, Cisneros GS, Chu J, Winestone LE, Higham CS, Shimano KA, Kharbanda S, Avagyan S, Pauerstein P, Huang JN, Cheng G, Waters E, Winger BA, Cowan MJ, Long-Boyle JR. Younger children with nonmalignant disease have increased incidence of mixed myeloid chimerism after allogeneic hematopoietic cell transplantation with busulfan-based conditioning. Transplant Cell Ther. 2025 Apr; 31(4):259.e1-259.e15.  View on PubMed
  3. Eissa H, Cowan MJ, Heimall J. Late effects following hematopoietic cell transplantation for severe combined immunodeficiency: critical factors and therapeutic options. Expert Rev Clin Immunol. 2025 Jan; 21(1):73-82.  View on PubMed
  4. Miranda MA, Tsalatsanis A, Trotter JR, Arnold DE, Squire JD, Kidd S, Parikh S, Marsh RA, Griffith LM, Mallhi K, Chellapandian D, Lim SS, Grunebaum E, Sullivan KE, Newburger PE, Dinauer MC, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Malech HL, Kang EM, Morton FB, Leiding JW. High symptom burden in female X-linked chronic granulomatous disease carriers. Clin Immunol. 2024 Nov; 268:110364.  View on PubMed
  5. Abraham RS, Basu A, Heimall JR, Dunn E, Yip A, Kapadia M, Kapoor N, Satter LF, Buckley R, O'Reilly R, Cuvelier GDE, Chandra S, Bednarski J, Chaudhury S, Moore TB, Haines H, Dávila Saldaña BJ, Chellapandian D, Rayes A, Chen K, Caywood E, Chandrakasan S, Lugt MTV, Ebens C, Teira P, Shereck E, Miller H, Aquino V, Eissa H, Yu LC, Gillio A, Madden L, Knutsen A, Shah AJ, DeSantes K, Barnum J, Broglie L, Joshi AY, Kleiner G, Dara J, Prockop S, Martinez C, Mousallem T, Oved J, Burroughs L, Marsh R, Torgerson TR, Leiding JW, Pai SY, Kohn DB, Pulsipher MA, Griffith LM, Notarangelo LD, Cowan MJ, Puck J, Dvorak CC, Haddad E. Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia. Clin Immunol. 2024 04; 261:109942.  View on PubMed
  6. Grunebaum E, Arnold DE, Logan B, Parikh S, Marsh RA, Griffith LM, Mallhi K, Chellapandian D, Lim SS, Deal CL, Kapoor N, Murguía-Favela L, Falcone EL, Prasad VK, Touzot F, Bleesing JJ, Chandrakasan S, Heimall JR, Bednarski JJ, Broglie LA, Chong HJ, Kapadia M, Prockop S, Dávila Saldaña BJ, Schaefer E, Bauchat AL, Teira P, Chandra S, Parta M, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Malech HL, Kang EM, Leiding JW. Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: A Primary Immune Deficiency Treatment Consortium study. J Allergy Clin Immunol. 2024 May; 153(5):1423-1431.e2.  View on PubMed
  7. Leiding JW, Arnold DE, Parikh S, Logan B, Marsh RA, Griffith LM, Wu R, Kidd S, Mallhi K, Chellapandian D, Si Lim SJ, Grunebaum E, Falcone EL, Murguia-Favela L, Grossman D, Prasad VK, Heimall JR, Touzot F, Burroughs LM, 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 LA, Ebens CL, Madden LM, DeSantes K, Milner J, Rangarajan HG, Shah AJ, Gillio AP, Knutsen AP, Miller HK, Moore TB, Graham P, Bauchat A, Bunin NJ, Teira P, Petrovic A, Chandra S, Abdel-Azim H, Dorsey MJ, 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 12 14; 142(24):2105-2118.  View on PubMed
  8. 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 10 06; 9(40):eadg9959.  View on PubMed
  9. Eissa H, Thakar MS, Shah AJ, Logan BR, Griffith LM, Dong H, Parrott RE, O'Reilly RJ, Dara J, Kapoor N, Forbes Satter L, 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, Vander Lugt MT, Mousallem TI, Oved JH, Dorsey M, Abdel-Azim H, Martinez C, Bleesing JH, 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. Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study. J Allergy Clin Immunol. 2024 01; 153(1):287-296.  View on PubMed
  10. 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 LD, 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 12; 152(6):1619-1633.e11.  View on PubMed
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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

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