Igor Slukvin, MD, PhD

Portrait of Igor Slukvin, MD, PhD
Professor
Pathology and Laboratory Medicine
Address: 
Room 102 Primate
1220 Capitol Court
Madison, WI 53715
Telephone: 
(608) 263-0058
Focus Groups: 
Immunology/Immunopathology
Education: 
MD, Kiev Medical Institute, Kiev, Ukraine
PhD, Kiev Institute of Pediatrics, Obstetrics, and Gynecology
Research Summary: 
Hematopoietic development from pluripotent stem cells; de novo generation of hematopoietic stem cells, modeling leukemia stem cells using reprogramming technologies
Research Detail: 

Hematopoietic stem cell transplantation has become the standard of care for treatment of many otherwise incurable diseases such as leukemia, lymphoma and multiple myeloma. In addition, hematopoietic stem cell transplantation is used for treatment of hereditary disorders such as anemia (sickle-cell anemia, beta-thalassemia, and aplastic anemia), inborn errors of metabolism, immunodeficiencies, and autoimmune diseases. However, insufficient numbers of hematopoietic stem cells, graft failure, inadequate anti-tumor immune response after transplantation, and graft-versus- host disease remain significant limitations to the success of hematopoietic stem cell transplantation. The main focus of research in my lab is to significantly advance the clinical use of stem cells through development of novel sources of hematopoietic stem cells and mature blood cells for transplantation, transfusion and cancer immunotherapy. We focused on the following strategies to generate alternative sources of therapeutic blood cells:

  1. Directed differentiation of human embryonic stem (hES) cells and inducedpluripotent stem (iPS) cells into the hematopoietic stem and mature blood cells.
  2. Reprogramming of pluripotent stem cells and non-hematopoietic somatic cells into the blood cells.

Using these methodologies, we anticipate generating immunologically compatible hematopoietic stem and immunotherapeutic cells in large quantities. In this way we can eliminate serious complications of bone marrow transplantation such as graft-versus-host disease and transplant failure, and at the same time generate a significant anti-tumor immune response.

We use integrative approaches, including genomics, proteomics and bioinformatics, to achieve the outlined goals and to understand important cellular, and molecular events leading to blood cell development and diversification. We already developed a very efficient system for hematopoietic and endothelial differentiation of hES and iPS cells, and directed differentiation of hES cells toward red blood cells, dendritic cells, macrophages, osteoclasts, and granulocytes. In addition, we defined the major cellular pathways leading to formation of blood cells and identified several novel hematoendothelial, hematopoietic and mesenchymal progenitors. Through comparative analysis of transcriptome and engraftment properties of these novel progenitors and fetal primitive blood cells as well as employing loss-of- and gain-on-function and lienage-tracing experiments, we expect to gain fundamental insights into molecular mechanisms leading to blood cell development. These studies could ultimately revolutionize cellular therapies for blood cancer and hereditary blood disease, and can be exploited for discovery of new drugs regulating hematopoietic stem cells, as well.

Selected Publications: 
GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition.Kang H, Mesquitta WT, Jung HS, Moskvin OV, Thomson JA, Slukvin II.Stem Cell Reports. 2018 May 24. pii: S2213-6711(18)30219-4. doi: 10.1016/j.stemcr.2018.05.002. [Epub ahead of print]PMID: 29861167
Activation of the Arterial Program Drives Development of Definitive Hemogenic Endothelium with Lymphoid Potential.Park MA, Kumar A, Jung HS, Uenishi G, Moskvin OV, Thomson JA, Slukvin II.Cell Rep. 2018 May 22;23(8):2467-2481. doi: 10.1016/j.celrep.2018.04.092.PMID: 29791856
NOTCH signaling specifies arterial-type definitive hemogenic endothelium from human pluripotent stem cells.Uenishi GI, Jung HS, Kumar A, Park MA, Hadland BK, McLeod E, Raymond M, Moskvin O, Zimmerman CE, Theisen DJ, Swanson S, J Tamplin O, Zon LI, Thomson JA, Bernstein ID, Slukvin II.Nat Commun. 2018 May 8;9(1):1828. doi: 10.1038/s41467-018-04134-7.PMID: 29739946
Functional Heterogeneity of Endothelial Cells Derived from Human Pluripotent Stem Cells.D'Souza SS, Kumar A, Slukvin II.Stem Cells Dev. 2018 Apr 15;27(8):524-533. doi: 10.1089/scd.2017.0238. Epub 2018 Mar 27.PMID: 29583085
Optimization of Synthetic mRNA for Highly Efficient Translation and its Application in the Generation of Endothelial and Hematopoietic Cells from Human and Primate Pluripotent Stem Cells.Suknuntha K, Tao L, Brok-Volchanskaya V, D'Souza SS, Kumar A, Slukvin I.Stem Cell Rev. 2018 Mar 8. doi: 10.1007/s12015-018-9805-1. [Epub ahead of print]PMID: 29520567
Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts.Kumar A, D'Souza SS, Moskvin OV, Toh H, Wang B, Zhang J, Swanson S, Guo LW, Thomson JA, Slukvin II.Cell Rep. 2017 May 30;19(9):1902-1916. doi: 10.1016/j.celrep.2017.05.019.PMID: 28564607
Reprogramming cell fate with a genome-scale library of artificial transcription factors.Eguchi A, Wleklinski MJ, Spurgat MC, Heiderscheit EA, Kropornicka AS, Vu CK, Bhimsaria D, Swanson SA, Stewart R, Ramanathan P, Kamp TJ, Slukvin I, Thomson JA, Dutton JR, Ansari AZ. Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):E8257-E8266. doi: 10.1073/pnas.1611142114. Epub 2016 Dec 5.PMID: 27930301
A human VE-cadherin-tdTomato and CD43-green fluorescent protein dual reporter cell line for study endothelial to hematopoietic transition.Jung HS, Uenishi G, Kumar A, Park MA, Raymond M, Fink D, McLeod E, Slukvin I.Stem Cell Res. 2016 Sep;17(2):401-405. doi: 10.1016/j.scr.2016.09.004. Epub 2016 Sep 13.PMID: 27879215
Wnt signaling inhibitor FH535 selectively inhibits cell proliferation and potentiates imatinib-induced apoptosis in myeloid leukemia cell lines.Suknuntha K, Thita T, Togarrati PP, Ratanachamnong P, Wongtrakoongate P, Srihirun S, Slukvin I, Hongeng S.Int J Hematol. 2017 Feb;105(2):196-205. doi: 10.1007/s12185-016-2116-x. Epub 2016 Oct 20.PMID: 27766528
Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity.Hafner AL, Contet J, Ravaud C, Yao X, Villageois P, Suknuntha K, Annab K, Peraldi P, Binetruy B, Slukvin II, Ladoux A, Dani C.Sci Rep. 2016 Aug 31;6:32490. doi: 10.1038/srep32490.PMID: 27577850