Igor I. Slukvin, MD, PHD

Position title: Professor, Pathology & Laboratory Medicine

Email: islukvin@wisc.edu

Phone: 608-263-0058

Organ System/Disease Focus:
Blood development/disease
Aligned Research Focus:
Hematopoietic and endothelial development from human pluripotent stem cells, hematopoietic stem cell (HSC) biology
Igor Sluvkin headshot

Pubmed

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Research Description:

Pluripotent stem (PS) cells, including embryonic stem (ES) and induced pluripotent stem (iPS) cells, represent a unique population of cells capable of self-renewal and differentiation. PS cells can form any cell type in the body and serve as a scalable cell source for transplantation and tissue engineering. The main focus of my research is to establish the differentiation of human PS cells into hematopoietic progenitors and mature blood cells in order to understand molecular mechanisms of early hematopoietic specification and provide a novel source of cells for bone marrow transplantation, transfusion and cancer immunotherapy. My laboratory identified the major cellular and molecular pathways leading to blood, endothelial, and mesenchymal stem/stromal cell formation from human and nonhuman primate (NHP) pluripotent stem cells (ESC/iPSCs), and was the first to identify a set of markers and assays that precisely distinguishes hematopoietic progenitors, hemogenic, non-hemogenic endothelium and arterial hemogenic endothelium, and mesenchymal progenitors in PS cell cultures. We also contributed to the initial reports on reprogramming primate somatic cells to iPS cells, and pioneered a transgene-free technology for the reprogramming of blood cells to iPS cells. We developed several protocols for scalable production of hematopoietic progenitors and mature cells of erythroid, myeloid and lymphoid lineages from human and NHP iPS cells and mastered novel technologies for genetic engineering of iPS cells. Currently, my laboratory is working on 1) identification of cellular pathways leading to specification hemogenic endothelium with definitive lymphomyeloid potential, 2) developing preclinical models for novel bone marrow transplantation technologies, including iPSC-based therapies for bone marrow failure and immunotherapies for AIDS, and 3) developing of novel iPS cell-based immunotherapies for solid cancers.

Selected References:
  • D’Souza SS, Kumar A, Maufort J, Weinfurter JT, Raymond M, Strelchenko N, Perrin E, Coonen J, Mejia A, Simmons H, Torbett BE, Reynolds M, Thomson JA, Slukvin I. Assessment of Safety and Immunogenicity of MHC homozygous iPSC-derived CD34+ Hematopoietic Progenitors in a NHP Model. Blood Adv. 2022 Apr 11:bloodadvances.2022006984. doi: 10.1182/bloodadvances.2022006984. Online ahead of print.
  • Jung HS, Uenishi G, Park MA, Liu P, Suknuntha K, Raymond M, Choi YJ, Thomson JA, Ong IM, Slukvin II. SOX17 integrates HOXA and arterial programs in hemogenic endothelium to drive definitive lympho-myeloid hematopoiesis. Cell Rep. 2021 Feb 16;34(7):108758. doi: 10.1016/j.celrep.2021.108758. PMID: 33596423
  • D’Souza SS, Bennett S, Kumar A, Kelnhofer LE, Weinfurter J, Suknuntha K, Coonen J, Mejia A, Simmons H, Golos T, Hematti P, Capitini CM, Reynolds MR, Slukvin II. Transplantation of T-cell receptor α/β-depleted allogeneic bone marrow in nonhuman primates.
    Exp Hematol. 2021 Jan;93:44-51. doi: 10.1016/j.exphem.2020.09.198. Epub 2020 Nov 8.
    PMID: 33176119
  • Bloor AJC, Patel A, Griffin JE, Gilleece MH, Radia R, Yeung DT, Drier D, Larson LS, Uenishi GI, Hei D, Kelly K, Slukvin I, Rasko JEJ. Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Nature Medicine. 2020 Nov;26(11):1720-1725. doi: 10.1038/s41591-020-1050-x. Epub 2020 Sep 14. PMID: 32929265.
  • Brok-Volchanskaya V.S., Bennin D. A., Suknuntha K, Klemm L. C., Huttenlocher A., Slukvin I. Effective and rapid generation of functional neutrophils from induced pluripotent stem cells using ETV2 modified mRNA. Stem Cell Reports. 2019 Dec 10;13(6):1099-1110.