Colin L. Sweeney, Ph.D.

Genetic Immunotherapy Section

Colin L. Sweeney, Ph.D.

Staff Scientist, Genetic Immunotherapy Section

Contact: For contact information, search the NIH Enterprise Directory.

Provides direct clinical care to patients at NIH Clinical Center

Major Areas of Research

  • Major areas of research: Induced pluripotent stem cells (reprogramming and differentiation), Hematopoietic stem cell biology and hematopoiesis, Genome editing of stem cells
  • Disease focus: Chronic Granulomatous Disease

Program Description

Colin Sweeney provides core expertise and training to laboratories in NIAID on induced pluripotent stem cells (iPSCs), including collaborations with investigators throughout NIAID to perform iPSC reprogramming of patient samples and differentiation of iPSCs into mature cell types of interest for the modeling of disease phenotypes and immune responses, as well as performing genome editing of iPSCs and other cell types with CRISPR/Cas9 for gene knockout studies, gene repair, or targeted transgene insertion. He has developed efficient iPSC reprogramming protocols using small volumes of patient blood samples or cryopreserved mononuclear cells as well as developing and utilizing iPSC differentiation protocols for production of specific cell lineages, including fibroblasts, neural stem cells, neurons, astrocytes, hematopoietic stem/progenitor cells, monocytes/macrophages, dendritic cells, and microglia. In his research as a member of the Malech lab in the Genetic Immunotherapy Section, he has utilized patient-derived iPSCs for preclinical modeling of gene therapy strategies for treatment of Chronic Granulomatous Disease (CGD), including testing of therapeutic gene vector designs and identifying critical regulatory elements within the CYBB gene that are necessary to achieve normal physiological levels of expression after gene editing for treatment of X-linked CGD, and subsequently confirmed these findings in X-linked CGD patient hematopoietic stem cells as a relevant target cell type for clinical gene therapy. In follow-up assessments of clinical trial patients receiving lentiviral vector-based gene therapy for treatment of X-linked severe combined immunodeficiency, he has utilized iPSCs derived from post-treatment patient hematopoietic stem cells to study the effects of cryptic transcript splicing from the therapeutic lentiviral vector on aberrant clonal hematopoietic outgrowth after hematopoietic stem cell transplant, to develop vector safety modifications that eliminate cryptic splice sites.



Ph.D., 2003, University of Minnesota

Colin Sweeney received baccalaureate degrees in Biology and Computer Science from the University of Minnesota – Morris in 1997 and a Ph.D. from the Microbiology, Immunology, and Molecular Pathobiology program at the University of Minnesota in 2003. He received further training as a Postdoctoral Fellow in the laboratory of Dr. Stanton Gerson at Case Western Reserve University and in the laboratory of Dr. Harry Malech at NIAID, before joining Dr. Malech’s lab as a Staff Scientist in 2016.

Selected Publications

De Ravin SS, Liu S, Sweeney C, Brault J, Whiting-Theobald N, Ma M, Liu T, Choi U, Lee J, Anaya-O'Brien S, Quackenbush P, Estwick T, Karra A, Docking E, Kwatemaa N, Guo S, Su L, Sun D, Zhou S, Puck J, Cowan M, Notarangelo L, Kang E, Malech H, Wu X. Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked Severe Combined Immunodeficiency. Nature Communications. In press.

Sweeney CL, Pavel-Dinu M, Choi U, Brault J, Liu T, Koontz S, Li L, Theobald N, Lee J, Bello EA, Wu X, Meis RJ, Dahl GA, Porteus MH, Malech HL, De Ravin SS. Correction of X-CGD patient HSPCs by targeted CYBB cDNA insertion using CRISPR/Cas9 with 53BP1 inhibition for enhanced homology-directed repair. Gene Ther. 2021 Jun;28(6):373-390.

Zhang ZZ, Zhang Y, He T, Sweeney CL, Baris S, Karakoc-Aydiner E, Yao Y, Ertem D, Matthews HF, Gonzaga-Jauregui C, Malech HL, Su HC, Ozen A, Smith KGC, Lenardo MJ. Homozygous IL37 mutation associated with infantile inflammatory bowel disease. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2009217118.

Sweeney CL, Merling RK, De Ravin SS, Choi U, Malech HL. Gene Editing in Chronic Granulomatous Disease. Methods Mol Biol. 2019;1982:623-665.

Sweeney CL, Zou J, Choi U, Merling RK, Liu A, Bodansky A, Burkett S, Kim JW, De Ravin SS, Malech HL. Targeted Repair of CYBB in X-CGD iPSCs Requires Retention of Intronic Sequences for Expression and Functional Correction. Mol Ther. 2017 Feb 1;25(2):321-330.

Sweeney CL, Teng R, Wang H, Merling RK, Lee J, Choi U, Koontz S, Wright DG, Malech HL. Molecular Analysis of Neutrophil Differentiation from Human Induced Pluripotent Stem Cells Delineates the Kinetics of Key Regulators of Hematopoiesis. Stem Cells. 2016 Jun;34(6):1513-26.

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