University of Wisconsin–Madison

Regenerative and Reproductive Medicine (RRM) Scientific Working Group

Mother with babyThe RRM program is one of the core strengths of the WNPRC and a key component of the Stem Cell and Regenerative Medicine Center at UW-Madison. The first successful derivation of nonhuman primate and human embryonic stem cells by Dr. James Thomson positioned the WNPRC as a leader in stem cell biology and regenerative medicine. With advances in the understanding of pluripotent stem cell (PSC) biology and the derivation of induced pluripotent stem cells (iPSCs) from nonhuman primates and humans, WNPRC researchers collaborate with numerous campus and outside investigators on translational studies aimed at generating novel stem cell-based therapies for neurological disorders, blood and vascular diseases, HIV, diabetes, myocardial dysfunction, autoimmune diseases and musculoskeletal disorders and injuries.

The WNPRC has a long history of advances in reproductive health research, including the world’s first monkey born through in vitro fertilization. Major reproductive medicine studies today focus on understanding and treating a number of women’s health problems, such as pregnancy and birth complications, polycystic ovary syndrome and other infertility causes, and endometriosis.

Accomplishments:

  • The worlds first monkey born in 1984 through in vitro fertilization, leading to improvements in IVF techniques for animals and people. (Barry Bavister, Steve Eisele and colleagues)
  • Discovering that fetal testosterone exposure programs polycystic ovary syndrome (PCOS)-like neuroendocrine and metabolic dysfunction in female rhesus monkeys, leading to earlier diagnoses and interventions in treating PCOS in women. (David Abbott, Daniel Dumesic and Andrea Dunaif groups)
  • Successful isolation and culture of monkey embryonic stem cells at the Primate Center in 1995, human embryonic stem cells off site with private funding in 1998, and human induced pluripotent (iPS) cells in 2007. (James Thomson and colleagues: iPS cells by Thomson and Junying Yu and WNPRC support)
  • Establishing nonhuman primate models for preclinical evaluation of PSC-based therapies of Parkinson’s Disease. (Marina Emborg and Su-Chun Zhang groups)
  • Establishing MHC defined nonhuman primate models for bone marrow transplantation and transfusion of iPSC-derived blood products. (Igor Slukvin and James Thomson groups)
  • Successful gene modification in iPSCs using the CRISPR/Cas9 system, positioning the WNPRC to generate innovative models for gene and stem cell therapies for a number of diseases. (Su-Chun Zhang, James Thomson, Igor Slukvin groups)
  • Developing a new Precision Medicine Core, which will develop unique resources for the broad scientific community to study the pathogenesis of human genetic disease and provide the  platforms to test novel therapeutic approaches, including regenerative medicine induced pluripotent stem cells (iPSCs) therapies. (Igor Slukvin and James Thomson groups)

  • Establishing nonhuman primate models of renal and donor hematopoetic stem cell infusion to create conditions for mixed chimerism and drug free acceptance of the renal transplant (Dixon Kaufman, Peiman Hematti, Samuel Strober at Stanford Medicine)

Additional progress:

  • Cutting-edge imaging modalities for monitoring adverse pregnancy outcomes, focusing on pathogen-induced pregnancy loss, such as studying the impact of early pregnancy infection of macaques with Listeria monocytogenes on fetal and maternal well-being. (Ted Golos and collaborators in the Department of Pathobiological Sciences and the School of Veterinary Medicine.)
  • Establishing infrastructure and SOPs for daily monitoring of infected pregnant females for signs of adverse outcomes, and the experimental use of ultrasound for monitoring fetal well-being and placental integrity. (Ted Golos lab and infectious disease colleagues at the School of Veterinary Medicine)
  • Studying adverse pregnancy outcome in infection with Porphyromonas gingivalis, an oral pathogen associated with preterm labor and other adverse outcomes. (Leticia Reyes group)
  • Developing advanced, sensitive and safe MRI imaging to monitor placental function in normal and obese pregnancies, as obesity is often associated with adverse outcomes such as preeclampsia and fetal growth restriction. (Golos group and collaborators in Radiology and Medical Physics)
  • The infrastructure for monitoring adverse pregnancy outcomes, and the use of advanced imaging for placental and fetal well-being, perfectly positioned the WNPRC to be able to quickly initiate a study of the impact of maternal infection with Zika virus in pregnant rhesus monkeys, a major cross-disciplinary effort between the WNPRC Global Infectious Diseases group, the Regenerative and Reproductive Medicine group, collaborating UW-Madison arbovirologists, and infectious disease specialists in the US and Brazil. This is an outstanding example of the importance of the availability of broad scientific expertise at the NPRCs to be able to mount a nimble response to emerging national and international health challenges. (Numerous collaborating groups)
  • Using CRISPR Cas9 genome editing to target genes for novel models of Parkinson’s Disease in the common marmoset, and HIV infection in Mauritian cynomolgus macaques. (Ted Golos, Marina Emborg and Igor Slukvin).
  • Developing a novel monkey model for studying Type 1 ovarian cancer. (Manish Patankar OB/GYN group)
  • Developing marmoset models for safe administration of dexrazoxane to protect the ovaries and fertility of young female chemotherapy patients. (Sana Salih and David Abbott groups)
  • Developing a rhesus model for developing novel therapies for induction of labor in post-date patients, prediction of patients at greatest risk for preterm delivery, and monitoring of treatments for complications due to preterm or post-term births. (Tim Hall, Medical Physics, and Helen Feltovich, University of Utah)
  • Identifying genes and novel gene-environment interactions associated with the development of endometriosis through comparative studies with rhesus monkeys and women. (Joe Kemnitz, UW ICTR and collaborators at the Marshfield Clinic and Oxford University)
  • Studying neuroendocrine dysfunction in monkey and human models of polycystic ovary syndrome. (David Abbott and J. Levine groups, with John Marshall at the University of Virginia)
  • Developing MHC-defined NHP and CCR5-mutant NHP models for stem cell-based therapies of hematologic disorders and AIDS. (Igor Slukvin, Ted Golos, Reynolds, Peiman Hematti, Christian Capitini)
  • Developing nonhuman primate model for preclinical evaluation of haplotype-based iPSC banking for HLA-matched blood products. (Igor Slukvin, James Thomson, Matthew Reynolds, Thomas Raife)
  • Developing a MHC-defined non-human primate vascular transplant model to assess efficacy of HLA homozygous iPSC banks and preclinical evaluation of iPSC-based therapies for vascular disease. (James Thomson, Igor Slukvin, John Maufort, William Burlingham)

The RRM Working Group includes approximately 50 scientists, veterinarians and physicians from 17 universities, clinics and institutions.

Please direct research and collaboration queries to:

Ted Golos, Ph.D.
Phone: (608) 263-3567
Send email to Dr. Golos

Igor Slukvin, Ph.D.
Phone: (608) 265-8984
Send email to Dr. Slukvin