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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD065914-04
Application #
8508992
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Yoshinaga, Koji
Project Start
2010-08-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$131,718
Indirect Cost
$9,757
Name
Cornell University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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