MICaB Graduate Program
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Dan S. Kaufman, M.D., Ph.D.
Department of Medicine
Mayo Graduate School, 1994, Ph.D.
Mayo Medical School, 1996, M.D.
Hematopoietic and endothelial cell development from embryonic stem cells
Research in my lab uses embryonic stem (ES) cells to understand the earliest stages of blood development. Individuals produce billions of blood cells every day. The stimuli and genes that allow individual hematopoietic stem cells (HSCs) to produce mature progeny such as red blood cells, white blood cells, lymphocytes and platelets has been studied in considerable depth and serves as a model system in developmental biology. However, how the multipotent HSCs is derived during embryogenesis remains poorly understood, especially in the human system. My studies focus on this on this beginning stage of blood development: the transition from embryonic stem cell to hematopoietic stem cell.
Research in my lab has defined a method to derive multiple types of mature blood cells from human ES cells. In vitro and in vivo models are used to elucidate both extracellular protein interactions and intracellular genetic regulation that impact these developmental pathways. Currently, studies are underway to better define the conditions that support hematopoietic cells by addition of specific cytokines and growth factors, overexpression of exogenous genes in the ES cells, and by manipulation of the stromal cells to identify the role of specific proteins. Another portion of my current research aims to determine the in vivo potential of the human ES cell-derived hematopoietic cells. Proof of an ES cell-derived HSC requires evidence of long-term multilineage engraftment in vivo. Other aspects of my research involve use of human and rhesus monkey ES cells to study endothelial cell development and characterization of potential hemangioblast cells that serve as a common precursor to blood and endothelial cells.
Kaufman lab website
Selected Recent Publications:
- Ni, Zhenya, David A. Knorr, Laura Bendzick, Jeremy Allred and Dan S. Kaufman. (2014). Expression of chimeric receptor CD4ζ by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo. Stem Cells, 32:1021-31.
- Bock, Allison M., David A. Knorr, and Dan S. Kaufman. (2013). Development, expansion, and in vivo monitoring of human NK cells from hESCs and iPSCs. Journal of Visualized Experiments (JOVE). (74), e50337.
- Geller, Melissa A, David A. Knorr, David A. Hermanson, Lee Pribyl, Laura Bendzick, Valarie McCullar, Jeffrey S. Miller, and Dan S. Kaufman. (2013). Intraperitoneal delivery of human natural killer cells for treatment of ovarian cancer in a mouse xenograft model. Cytotherapy. 15, 1297-1306.
- Knorr, David A., Zhenya Ni, Melinda K. Hexum, Laura Bendzick, Laurence J. N. Cooper , Dean A. Lee,, and Dan S. Kaufman. (2013). Clinical Scale Derivation Of Natural Killer Cells From Human Pluripotent Stem Cells For Cancer Therapy. Stem Cells Translational Medicine. 2:274-83.
- Simara, Pavel, Jason A. Motl, and Dan S. Kaufman. Pluripotent Stem Cells and Gene Therapy. (2013). Translational Medicine (special issue on Gene Therapy). 161:284-92.
- Ni, Zhenya, David A. Knorr, Christine L. Clouser, Peter Southern, Louis M. Mansky, In-Hyun Park and Dan S. Kaufman. (2011).Human pluripotent stem cells produce natural killer cells that mediate anti-HIV-l activity by utilizing diverse cellular mechanisms. J. of Virology. 85:43-50.
- Kaufman, Dan S. (2009). Toward Clinical Therapies Utilizing Hematopoietic Cells Derived from Human Pluripotent Stem Cells. Blood, 114:3513-3523.
- Tian, Xinghui, Melinda K. Hexum, Vesselin R. Penchev, Russell J. Taylor, Leonard D. Shultz, and Dan S Kaufman. (2009). Bioluminescent imaging demonstrates transplanted human embryonic stem cell-derived CD34+ cells preferentially develop into endothelial cells. Stem Cells 27:2675-85.
- Woll, Petter S. Bartosz Grzywacz, Xinghui Tian, Rebecca Marcus, Michael R. Verneris and Dan S. Kaufman. (2009). Human embryonic stem cells differentiate into a unique population of natural killer cells with highly potent in vivo anti-tumor activity. Blood, 113:6094-6101.
- Martin, Colin H., Petter S. Woll, Juan-Carlos Zuniga-Pflucker and Dan S. Kaufman. (2008). Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells. Blood, 112: 2730-2737.
- Woll, Petter S. J.K. Morris, M.S. Painschab, R.K. Marcus, A.D. Kohn, T.L. Biechele, R.T. Moon, and D.S. Kaufman. 2008. Wnt signaling promotes hemato-endothelial cell development from human embryonic stem cells. Blood. 111: 122-131.
- Wilber, Andrew, Jonathan L. Linehan, Xinghui Tian, Petter S. Woll, Julie K. Morris, Lalitha R. Belur, R. Scott McIvor, and Dan S. Kaufman. 2007. Use of the Sleeping Beauty Transposon System for Genetic Engineering of Human Embryonic Stem Cell-derived Hematopoietic Cells. Stem Cells, 25; 2919-2927.
- Kaufman, Dan S., Eric T. Hanson, Rachel L. Lewis, Robert Auerbach, and James A. Thomson. 2001. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. USA. 98:10716-10721.