Ted Golos, PhD

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Endocrinology-Reproductive Physiology Program
Stem Cell and Regenerative Medicine Center

ALIGNED RESEARCH FOCUS

The maternal-fetal interface and reproductive tract immunology, embryonic genomic editing

ORGAN SYSTEM/DISEASE FOCUS

Recurrent pregnancy loss, female reproductive tract immunology, embryo implantation and placental biology, intrauterine/prenatal programming

RESEARCH DESCRIPTION

The Golos laboratory has two areas of focus. The lab examines questions of placental and reproductive tract biology relevant to human health and disease, using nonhuman primate models and trophoblast stem cells. Study of the maternal-fetal interface include the impact of pathogens (Zika virus, Listeria monocytogenes) on pregnancy success and the immune cell responses to maternal infection. In particular, why endometrial and placental immune cells can fail to protect the fetus from vertical pathogen transmission, while the mother may have little or no symptomatic disease. Placental cells are used to determine if extracellular vesicles shed into the circulation may provide a readout of placental health, and nanoparticles are being designed to target the placenta to be able to “treat the placenta” in cases of fetal growth restriction or other placental maladaptation. Finally, advanced techniques with magnetic resonance imaging have been developed and are being used in experimental models to induce inflammation and infarction at the maternal-fetal interface. Irregular or compromised utero-placental blood flow or placental function is associated with pregnancies that result in preeclampsia, miscarriage, preterm birth, and stillbirth. The ability to image utero-placental blood flow could be a predictive tool in adverse outcomes, and help develop ways to increase pregnancy success rates.

The lab also is working to develop of non-human primate models of human disease using embryonic genome editing. Recent advances in genetic engineering, by way of CRISPR-Cas9-mediated gene editing technology, provides a method for creating genetic mutations associated with human disease conditions in animal models. The non-human primate model more closely parallels humans allowing for the study of disease physiology to develop therapies and treatments of human diseases. Our lab is currently focusing on two targets, CCR5 which is associated with protection from AIDS, and CYP19A1, which is a critical gene in steroid hormone synthesis and associated with, for one example, with androgen excess in polycystic ovary syndrome. Using an in vitro fertilization system, we can introduce the CRISPR-Cas9 gene editing components into the early embryo, and transfer embryos to a surrogate monkey to initiate a pregnancy. The babies will be monitored as they develop and genetically tested to confirm that they have the genetic mutation. Those carrying the mutation can then be utilized for collaborating neurodevelopment studies to develop treatments and therapies for the disease.

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