Donald B. Kohn, M.D.
Professor, Microbiology, Immunology & Molecular Genetics; Pediatrics (Hematology/Oncology); Molecular & Medical Pharmacology. Member: Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, Tumor Immunology Program at the Jonsson Comprehensive Cancer Center (JCCC), UCLA Children’s Discovery and Innovation Institute; Immunity, Microbes & Molecular Pathogenesis GPB Home Area, Molecular Pharmacology GPB Home Area, Genetics & Genomics GPB Home Area; Center for Duchenne Muscular Dystrophy; Blood and Marrow Transplant Center, CTSI; Pilot and Collaborative Translational Clinical Studies Program.
The research in the Kohn lab focuses on the development of new methods to treated genetic diseases of blood cells by gene modification of hematopoietic stem cells. Dr. Kohn’s group was the first (and still the only one) to perform a clinical trial with gene transfer to umbilical cord blood CD34+ cells for a genetic disorder (ADA-SCID in 1993) and the first in the U.S. to initiate clinical trials of gene therapy for pediatric HIV/AIDS using bone marrow stem cells. Current projects include (1) performing clinical trials for ADA-deficient SCID, XSCID, Sickle Cell Disease and X-linked Chronic Granulomatous Disease, (2) developing new lentiviral vectors for regulated gene expression, (3) advancing techniques for site-specific gene editing for sickle cell disease and primary immune deficiency diseases, and (4) improving clinical hematopoietic stem cell processing. Our research group spans the bench-to-bedside spectrum and provides an excellent training environment for physician/scientists.
Donald B. Kohn, M.D. is Distinguished Professor of Microbiology, Immunology & Molecular Genetics (MIMG), Pediatrics and Molecular & Medical Pharmacology, the Director of the UCLA Human Gene and Cell Therapy Program, and is a member of the Broad Stem Cell Research Center, the Jonsson Comprehensive Cancer Center and the UCLA Children’s Discovery and Innovation Institute. He joined the faculty of UCLA in 2009. He received a B.S in Biology and an M.S. in Microbiology from the University of Illinois-Urbana and his MD in 1982 at the University of Wisconsin-Madison. He performed Pediatric Internship and Residency at the University of Wisconsin Hospitals and then a Medical Staff Fellowship in the Metabolism Branch of the National Cancer Institute of the NIH. He was at Children’s Hospital Los Angeles, USC Keck School of Medicine for 21 years, where he rose to the rank of Professor and served as the Head of the Division of Research Immunology/Bone Marrow Transplantation from 2002-2009. His research program studies gene therapy using hematopoietic stem cells, performing basic studies of gene transfer and expression and translating these findings to clinical trials of gene therapy for congenital immune deficiencies, sickle cell disease and other blood cell diseases. He was the President of the American Society of Gene and Cell Therapy (2003-2004) and President of the Clinical Immunology Society (2013-2014), served as a member (2010-15) and Chair (2013-15) of the Recombinant DNA Advisory Committee (RAC) for the NIH Office of Biotechnology. He was the recipient of an Elizabeth Glaser Scientist Award from the Pediatric AIDS Foundation and a Distinguished Clinical Scientist Award from the Doris Duke Charitable Foundation, and recently received a Lifetime Achievement Award from the Pediatric Blood & Marrow Transplant Consortium.
Masiuk KE, Laborada J, Roncarolo MG, Hollis RP and Kohn DB. Lentiviral Gene Therapy in HSCs Restores Lineage-Specific Foxp3 Expression and Suppresses Autoimmunity in a Mouse Model of IPEX Syndrome. Cell Stem Cells, In Press.
Lomova A, Clark DN, Miyahira EY, … and Kohn DB. Improving Gene Editing Outcomes in Human Hematopoietic Stem and Progenitor Cells by Temporal Control of DNA Repair. Stem Cells, In Press. PMID: 30372555
Kuo CY, Long JD, Campo-Fernandez B, … Hollis RP, Kohn DB. Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome. Cell Rep 23:2606-2616, 2018.
Urbinati F, Campo Fernandez B, Masiuk KE, Poletti V, Hollis RP, Koziol C, Kaufman ML, Brown D, Mavilio F, Kohn DB. Gene Therapy for Sickle Cell Disease: A Lentiviral Vector Comparison Study. Hum Gene Ther. 29:1153-1166, 2018. PMID: 30198339
Kohn DB, Hershfield MS, Puck JM, Aiuti A, Blincoe A, Gaspar HB, Notarangelo LD, Grunebaum E. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. 2018 Sep 5. [Epub ahead of print] PMID: 30194989
Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, Sadelain M. Gene therapy comes of age.
Science. 359(6372), 2018. Review. PMID: 29326244
Long J, Hoban MD, Cooper AR, Kaufman ML, Kuo CY, Campo-Fernandez B, Lumaquin D, Hollis RP, Wang X, Kohn DB, Romero Z. Characterization of Gene Alterations following Editing of the β-Globin Gene Locus in Hematopoietic Stem/Progenitor Cells. Mol Ther. 26:468-479, 2018. PMID: 29221806
Shaw KL, Garabedian E, Mishra S, …Kohn DB. Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency J Clin Invest, 127:1689-1699, 2017. PMID: 28346229
Morgan RA, Gray D, Lomova A, Kohn DB. Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned. Cell Stem Cell. 21:574-590, 2017. Review. PMID: 29100011
Masiuk KE, Brown D, Laborada J, Hollis RP, Urbinati F, and Kohn DB. Improving gene therapy efficiency through the enrichment of human hematopoietic stem cells. Mol Ther, 25:2163-2175, 2017. PMID: 28663101
Cooper AR, Lill GR, Shaw K, Carbonaro D, Davila A, Sokolic R, Candotti F, Pellegrini M, and Kohn DB. Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients. Blood, 129:2624-2635, 2017. PMID: 28351939 PMCID: PMC5428461
Hematol Oncol Clin North Am. 31:721-735, 2017. Review. PMID: 28895843
Kohn DB, Porteus MH, Scharenberg AM. Ethical and regulatory aspects of genome editing. Blood. 127:2553-60, 2016. Review. PMID: 27053531
Hoban MD, Lumaquin D, Kuo CY, …Kohn DB. CRISPR/Cas9-mediated correction of the sickle mutation in human CD34+ cells. Mol Ther. 24:1561-9, 2016.
Hoban MD, Cost GJ, Mendel MC, … and Kohn DB. Correction of the sickle-cell disease mutation in human hematopoietic stem/progenitor cells. Plenary Paper. Blood,125:2597-2604, 2015.
Baldwin K, Urbinati F, Romero Z, Campo-Fernandez B, Kaufman ML, Cooper AR, Masiuk K, Hollis RP, Kohn DB. Enrichment of human hematopoietic stem/progenitor cells facilitates transduction for stem cell gene therapy. Stem Cells. 33:1532-42, 2015. PMID: 25588820
Carbonaro DA, Zhang L, Jin X, Montiel-Equihua C, Geiger S, Carmo M, Cooper A, Fairbanks L, Kaufman ML, Sebire NJ, Hollis RP, Blundell MP, Senadheera S, Fu PY, Sahaghian A, Chan RY, Wang X, Cornetta K, Thrasher AJ, Kohn DB, Gaspar HB. Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Mol Ther. 22:607-622, 2014. PMID: 24256635
De Oliveira SN, Ryan C, Giannoni F, Hardee CL, Tremcinska I, Katebian B, Wherley J, Sahaghian A, Tu A, Grogan T, Elashoff D, Cooper LJ, Hollis RP, Kohn DB. Modification of hematopoietic stem/progenitor cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy.
Hum Gene Ther. 24:824-39, 2013. PMID: 23978226
Romero Z, Urbinati F, Geiger S, Cooper AR, Wherley J, Kaufman ML, Hollis RP, de Assin RR, Senadheera S, Sahagian A, Jin X, Gellis A, Wang X, Gjertson D, Deoliveira S, Kempert P, Shupien S, Abdel-Azim H, Walters MC, Meiselman HJ, Wenby RB, Gruber T, Marder V, Coates TD, Kohn DB. β-globin gene transfer to human bone marrow for sickle cell disease. J Clin Invest. 2013 Jul 1. PMID: 23863630
Giannoni F, Hardee CL, Wherley J, Gschweng E, Senadheera S, Kaufman ML, Chan R, Bahner I, Gersuk V, Wang X, Gjertson D, Baltimore D, Witte ON, Economou JS, Ribas A, Kohn DB. Allelic exclusion and peripheral reconstitution by TCR transgenic T cells arising from transduced human hematopoietic stem/progenitor cells. Mol Ther. 21:1044-54, 2013. PMID: 23380815
Carbonaro DA, Jin X, Wang X, Yu XJ, Rozengurt N, Kaufman ML, Wang X, Gjertson D, Zhou Y, Blackburn MR,and Kohn DB. Gene therapy/bone marrow transplant in ADA-deficient mice: roles of enzyme replacement therapy and cytoreduction. Blood. 120:3677-87, 2012.
Corrigan-Curay J, Cohen-Haguenauer O, O’Reilly Ma, … Zaia J, and Kohn DB. Challenges in vector and trial design using retroviral vectors for long-term gene correction in hematopoietic stem cell gene therapy. Molecular therapy : the journal of the American Society of Gene Therapy. 2012; 20(6): 1084-94.
Candotti F, Shaw KL, Muul L, …Kohn DB. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Plenary Paper. Blood 120: 3635-3646, 2012. PMCID: PMC3488882
Kohn Donald B, Candotti Fabio. Gene therapy fulfilling its promise. The New England journal of medicine. 2009; 360(5): 518-21.
Sumiyoshi T, Holt NG, Hollis RP, Ge S, Cannon PM, Crooks GM, Kohn DB. Stable transgene expression in primitive human CD34+ hematopoietic stem/progenitor cells, using the Sleeping Beauty transposon system. Hum Gene Ther. 20:1607-26, 2009.PMID: 19689196
Bahner I, Sumiyoshi T, Kagoda M, Swartout R, Peterson D, Pepper K, Dorey F, Reiser J, Kohn DB. Lentiviral vector transduction of a dominant-negative rev gene into human CD34+ hematopoietic progenitor cells potently inhibits human immunodeficiency virus-1 replication. Mol Ther 15:76-85, 2007. PMID: 17164778.
Podsakoff GM, Engel BC, Carbonaro DA, …Kohn DB. Selective survival of peripheral blood lymphocytes in children with HIV-1 following delivery of an anti-HIV gene to bone marrow CD34(+) cells. Mol Ther 12:77-86, 2005. PMID: 15963923.
Chan B, Wara D, Bastian J, Hershfield MS, Bohnsack J, Azen CG, Parkman R, Weinberg K, Kohn DB. Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID). Clin Immunol. 117:133-43, 2005. PMID: 16112907
Case S, Price M, Jordan CT, Xu D, Bauer G, Yu XJ, Wang L, Stripecke R, Naldini L, Kohn DB, and Crooks GM. Stable and efficient transduction of CD34+/CD38- human hematopoietic cells by HIV-1 based lentiviral vectors. Proc Natl Acad Sci (USA) 96:2988-93, 1999. PMCID: PMC15882
Kohn DB, Bauer G, Rice CR, … Church J. A clinical trial of retroviral-mediated transfer of a REV-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children. Blood 94:368-71, 1999. PMID: 10381536.
Kohn DB, Hershfield MS, Carbonaro D, Shigeoka A, Brooks J, Smogorzewska EM, Barsky LW, Chan R, Burotto F, Annett G, Nolta JA, Crooks G, Kapoor N, Elder M, Wara D, Bowen T, Madsen E, Snyder FF, Bastian J, Muul L, Blaese RM, Weinberg K, Parkman R. T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates. Nat Med. 1998 Jul;4(7):775-80. PMID: 9662367
Nolta JA, Dao MA, Wells S, Smogorzewska EM, Kohn DB. Transduction of pluripotent human hematopoietic stem cells demonstrated by clonal analysis after engraftment in immune deficient mice. Proc Natl Acad Sci USA 93:2414-19, 1996. PMCID: PMC39811
Kohn DB, Weinberg K, Nolta, J, et al. Engraftment of gene-modified umbilical cord blood cells in neonates with adenosine deaminase deficiency. Nature Medicine, 1:1017-23, 1995. PMC3013367
Bahner I, Zhou C, Yu XJ, Hao QL, Guatelli JC, Kohn DB. Comparison of trans-dominant inhibitory mutant human immunodeficiency virus type 1 genes expressed by retroviral vectors in human T lymphocytes. J Virol 67:3199-207, 1993. PMC237659.
Nolta JA, Crooks GM, Overell RW, Williams DE, Kohn DB. Retroviral vector-mediated gene transfer into primitive human hematopoietic progenitor cells: effects of mast cell growth factor (MGF) combined with other cytokines. Exp Hematol. 20:1065-71, 1992. PMID: 1281784
Nolta JA, Kohn DB. Comparison of the effects of growth factors on retroviral vector-mediated gene transfer and the proliferative status of human hematopoietic progenitor cells. Human Gene Ther 1:257-68, 1990. PMID: 2081193