OHSU

Shoukhrat Mitalipov

Totipotent and pluripotent stem cells are important as a unique research tool that allows investigation of the mechanisms regulating early primate development and differentiation. Human stem cells also provide the far-reaching foundation for the field of regenerative medicine and offer hope for the treatment of a wide range of clinical conditions that can be attributed to the loss or malfunction of specific cell types. Translational research in the clinically relevant nonhuman primate model is highly desirable to evaluate the safety, feasibility and efficacy of cell-based therapies. The basic research conducted in the lab provides new insights into the generation, maintenance and developmental potential of primate totipotent and pluripotent stem cells.


The overall research goal of Dr. Mitalipov's lab is to use molecular and cellular approaches to answer scientifically and clinically pertinent questions regarding gamete, embryo and stem cell biology. The main focus of ongoing and future studies is to understand the genetic and epigenetic mechanisms responsible for reprogramming of somatic cells to the totipotent and/or pluripotent state using somatic cell nuclear transfer (SCNT) and iPS cell technologies. Specifically, we are interested in the role of mitochondria and mitochondrial genome (mtDNA) in reprogramming and re-setting the developmental program in experimental totipotent and pluripotent cells derived from aged somatic cells. The objective is to develop efficient protocols for deriving "naïve" primate pluripotent cells via SCNT into oocytes or direct reprogramming.  Another goal is to test the developmental potential of experimental totipotent and pluripotent cells generated from somatic cells in chimera assays. Several other projects in the lab are focused on the assessment of the safety and efficacy of stem cell based therapies by transplantation studies in a clinically relevant nonhuman primate model.

The Mitalipov lab also investigates novel gene therapy approaches designed to prevent transmission of gene defects from parents to their children. Mutations in mtDNA contribute to a diverse range of still incurable human diseases that are maternally inherited through the egg's cytoplasm.  It is estimated that at least 1 in 200 born children inherit mtDNA mutation that may lead to disease. Mitalipov's team has pioneered the mitochondrial genome replacement approach in mature oocytes and demonstrated that the reconstructed oocytes with the donor mtDNA are capable of supporting normal fertilization, embryo development and produced healthy monkey offspring. This discovery suggest that the nuclear genetic material from a patient's egg containing mtDNA mutations could be removed, and transplanted into an enucleated egg containing normal mtDNA donated by a healthy female. A child born following fertilization with the husband's sperm would be free of risk from maternal mtDNA mutations as well as the authentic biological child of the patients. The overall goal of ongoing research initiative in Mitalipov lab is to translate these preclinical and clinical studies into clinical trials evaluating efficacy and long-term safety in families affected by mtDNA disease.

For more information visit Mitalipov Lab webpage.

 

BIOGRAPHY   

Shoukhrat Mitalipov is a Senior Scientist in the Division of Reproductive & Developmental Sciences of ONPRC, and a Director of the newly formed Center for Embryonic Cell and Gene Therapy. He earned his Ph.D. degree in Developmental & Stem Cell Biology at the Research Center for Medical Genetics in Moscow, Russia. He came to Utah State University in 1995 to conduct his postdoctoral research in stem cell and developmental biology. Dr. Mitalipov moved to the center in 1998.


KEY PUBLICATIONS

Kang E, Wu G, Ma H, Li Y, Tippner-Hedges R, Tachibana M, Sparman M, Wolf DP, Schöler HR, Mitalipov S. Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos. Nature. 2014 Mar 26. PMID: 24670652

Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R, Ma H, Kang E, Fulati A, Lee HS, Sritanaudomchai H, Masterson K, Larson J, Eaton D, Sadler-Fredd K, Battaglia D, Lee D, Wu D, Jensen J, Patton P, Gokhale S, Stouffer RL, Wolf D, Mitalipov S. Human embryonic stem cells derived by somatic cell nuclear transfer. Cell. 2013 Jun 6;153(6):1228-38. PMID: 23683578

Tachibana M, Amato P, Sparman M, Woodward J, Sanchis DM, Ma H, Gutierrez NM, Tippner-Hedges R, Kang E, Lee HS, Ramsey C, Masterson K, Battaglia D, Lee D, Wu D, Jensen J, Patton P, Gokhale S, Stouffer R, Mitalipov S. Towards germline gene therapy of inherited mitochondrial diseases. Nature. 2013 Jan 31;493(7434):627-31. PMID:23103867
 
Tachibana M, Sparman M, Ramsey C, Ma H, Lee HS, Penedo MC, Mitalipov S. Generation of chimeric rhesus monkeys. Cell. 2012 Jan 20;148(1-2):285-95. PMID: 22225614

Tachibana M, Sparman M, Sritanaudomchai H, Ma H, Clepper L, Woodward J, Li Y, Ramsey C, Kolotushkina O, Mitalipov S. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature. 2009 Sep 17;461(7262):367-72. PMID: 19710649

Byrne JA, Pedersen DA, Clepper LL, Nelson M, Sanger WG, Gokhale S, Wolf DP, Mitalipov SM. Producing primate embryonic stem cells by somatic cell nuclear transfer.  Nature. 2007 Nov 22;450(7169):497-502. PMID: 18004281

 

See a full listing of Dr. Mitalipov's publications