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 laboratory 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 cell nuclei to the oocyte-like state after transfer into oocyte cytoplasm. Specifically, we are interested in the role of oocyte cytoplasmic factors including mitochondria and mitochondrial genome (mtDNA) in reprogramming and re-setting the developmental program in transplanted nuclei. The objective is to develop efficient protocols for deriving "reconstructed" primate gametes via nuclear transfer into oocyte cytoplasm. Another goal is to test the developmental potential of experimental gametes and totipotent and pluripotent cells in monkeys. 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. Inherited pathogenic mutations contribute to a diverse range of still incurable human diseases. Mitalipov's team has pioneered the mitochondrial replacement therapy (MRT) and demonstrated that the entire mtDNA complement in oocytes can be replaced with the donor material. Reconstructed oocytes with donor mtDNA are capable of supporting normal fertilization, embryo development and produced healthy monkey offspring. This discovery suggest that the mutant mtDNA from a patient's egg could be removed, and replaced with 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 of MRT in families affected by mtDNA disease.
For more information visit Mitalipov Lab webpage.
Shoukhrat Mitalipov is a Professor in the Division of Reproductive &Developmental Sciences of ONPRC, and a Director of the OHSU 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 ONPRC in 1998.
KEY PUBLICATIONSTachibana 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, 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
See a full listing of Dr. Mitalipov's publications