Jeffrey A Yoder, Ph.D.
Associate Professor, College of Veterinary Medicine, Department of Molecular Biomedical Sciences
B.S., Biotechnology - Worcester Polytechnic Institute, Worcester, MA, 1990
Ph.D., Cell and Developmental Biology - Harvard University, Cambridge, MA
(Tim Bestor), 1998
Post-doctoral fellow - University of South Florida, Children's Research
Institute, St. Petersburg, FL (Gary Litman), 1998-2002
The overall goal of the Yoder lab is to utilize comparative genomics, molecular biology and biochemistry to identify and functionally characterize novel innate immune response genes. The two major projects of the lab are listed below:
Species ranging from humans to fish, frogs and reptiles possess natural cytotoxic cells as part of the innate immune system that recognize and destroy “non-self” or foreign antigens. Mammalian natural killer (NK) cells utilize inhibitory and activating cell surface receptors to differentiate between “normal” cells and virally infected or transformed cells. In general, inhibitory (non-killing) NK receptors (NKRs) recognize MHCI as a marker of “self” which stimulates a signaling cascade leading to the inhibition of NK mediated target lysis. In contrast, certain activating (killing) NKRs have been shown to recognize virally encoded or stress-related proteins and stimulate a signaling cascade leading to target cell destruction. Such activation of NK cells can also occur when endogenous MHCI is down regulated as in certain types of tumors. These signaling cascades within NK cells must be carefully balanced because defects in NK function can result in tumor progression or an autoimmune response, both presenting dangerous consequences to the individual. Although much is known about mammalian NKRs, only limited information is known about NKRs in non-mammalian model species.
Multi-gene families of mammalian NKRs are encoded by the leukocyte receptor complex (e.g. KIRs), the natural killer complex (e.g. Ly49s) and the CD94/NKG2 complex. NKRs can be further classified based on their extra-cellular domains: possessing either immunogobulin domains (KIRs) or C-type lectin domains (Ly49s and NKG2). Our laboratory is working on identifying and characterizing the functional orthologs of NKRs in bony fish, primarily using zebrafish as a model species.
The vertebrate immune response is comprised of multiple molecular and cellular components that must interface to provide the host species with an adequate defense against pathogens. Although much information is available on how individual molecules or cells respond to infection, a complete understanding of the whole-organism response to pathogen exposure remains unresolved, due to the dynamic complexity of the immune system and its interdependent innate and adaptive functionality. The zebrafish larva provides a unique model for overcoming this obstacle as the larva successfully defends itself from pathogens while lacking a functional adaptive immune system for the first 4-6 weeks of life, making it possible to examine exclusively the innate immune response in a whole-organism context. In transcriptional profiling studies it was found that novel genes that respond to pathogen associated molecular patterns in the zebrafish larva, also respond to infection stimuli in adult zebrafish and mice, underscoring the utility of this novel innate immune model for gene discovery.
We hypothesize that the transcriptional response of zebrafish larvae to infection stimuli will reveal novel genes that mediate innate immunity in mammals. In order to test this hypothesis, we are employing a novel zebrafish larvae assay to determine the whole-organism transcriptional response to pathogen stimuli in the absence of adaptive immunity, and validating the role of functionally uncharacterized pathogen-responsive “target” genes in zebrafish, mouse and human innate immune response. The long range goal of the proposed research is to define and evaluate the role of these “target” genes during the immune response in the context of the whole organism. This and future research constitute a complementary, multi-organism paradigm for investigating, evaluating and modulating the vertebrate innate immune response.
See complete publication list at: http://publicationslist.org/Jeff_Yoder
Debra Tokarz, DVM: Graduate Student, email@example.com
Jessica Romanet: DVM/PhD Student, firstname.lastname@example.org
Iván Rodriguez, PhD: Post-doc, email@example.com
Hayley Dirscherl: Graduate Student, firstname.lastname@example.org
Dustin Wcisel: Graduate Student, email@example.com
Amanda Kortum: DVM/PhD student, firstname.lastname@example.org