This application seeks support for advanced laboratory training for a specialty board certified (ACVIM) veterinarian completing the finals stages of preparation for a career as a translational scientist. The applicant would work in the laboratory of Dr. Douglas F. Antczak at the Baker Institute for Animal Health in the College of Veterinary Medicine at Cornell University. The proposed mentor has a 30 year history of NIH support for basic research in pregnancy immunology, and an outstanding record of training graduate students and post-doctoral scientists. The overall research environment at Cornell is exceptionally strong in the relevant disciplines of immunology, genetics, and reproductive biology. The applicant's project would use a unique model in pregnancy immunology to address important issues in immune tolerance and delivery of biologically active molecules through allogeneic cell therapy. Studies in several species of mammals have identified novel mechanisms that protect the developing fetus from recognition and / or destruction by the maternal immune system during pregnancy, but much remains to be discovered. The Antczak laboratory has developed a system for transplanting invasive trophoblast cells to ectopic sites outside the uterus in non-pregnant recipient animals. The research would focus on the effects of serial transplantation of invasive trophoblast into individual recipients. The experiments would test the hypothesis that established, functional trophoblast grafts create a tolerogenic local immunological environment dominated by regulatory T cells, and that these grafts would influence the immune responses mounted to secondary and subsequent trophoblast grafts. In the initial years the applicant would work closely with Dr. Antczak to master new techniques and to learn approaches to establishing and maintaining a basic research program. In the final years it is expected that the candidate would make the transition to independence, either remaining at the Baker Institute as a junior faculty member or moving to another institution in a permanent faculty position.

Public Health Relevance

This research would exploit a new model for unraveling the mechanisms by which the mammalian fetus escapes recognition and destruction by the maternal immune system during pregnancy. The experiments would focus on the trophoblast cells of the placenta that form the barrier between mother and fetus. This research has relevance to human fertility and infertility, and also to clinical organ transplantation.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Clinical Investigator Award (CIA) (K08)
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Pediatrics Subcommittee (CHHD)
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Yoshinaga, Koji
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Cornell University
Veterinary Sciences
Schools of Veterinary Medicine
United States
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Brosnahan, Margaret M; Silvela, Emily J; Crumb, Jessica et al. (2016) Ectopic Trophoblast Allografts in the Horse Resist Destruction by Secondary Immune Responses. Biol Reprod 95:135
Brosnahan, Margaret M; Miller, Donald C; Adams, Mackenzie et al. (2012) IL-22 is expressed by the invasive trophoblast of the equine (Equus caballus) chorionic girdle. J Immunol 188:4181-7
Brosnahan, M M; Brooks, S A; Antczak, D F (2010) Equine clinical genomics: A clinician's primer. Equine Vet J 42:658-70