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 three 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.
The zebrafish has become a powerful tool for dissecting vertebrate gene function during embryogenesis. Many systems have been developed for examining gene function in zebrafish, the most popular being transgenics for amplifying gene function and anti-sense strategies for knocking down gene function. However, only a few systems have been developed that permit spatio-temporal control of gene or transgene expression in the zebrafish embryo. More importantly, no system has been developed that is switchable, where individual genes or transgenes can be turned ON and OFF with a high degree of temporal, spatial, and quantitative control during development.
Our lab is collaborating with Alex Deiters' laboratory in the Department of Chemistry here at NCSU in order to develop and provide to the zebrafish community novel, switchable gene control systems for dissecting gene function in a spatio-temporal manner during zebrafish embryogenesis. The goal of our lab is to utilize these novel systems to inactivate immune-response genes during the larval stage of zebrafish development.
See complete publication list at: http://publicationslist.org/Jeff_Yoder
Yoder, J.A., M.G. Mueller, C. Wei, B. Corliss, D.M. Prather, T. Willis, R.T. Litman, J. Djeu and G.W. Litman. 2001. Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor complex. Proc Natl Acad Sci U S A. 98: 6771-6776. [MANUSCRIPT]
Litman, G.W., N.A. Hawke and J.A. Yoder. 2001. Novel immune-type receptors. Immunol Rev. 181: 250-259. [ABSTRACT]
Hawke, N.A., J.A. Yoder, R.N. Haire, M.G. Mueller, R.T. Litman, A.L. Miracle, T. Stuge, N. Miller and G.W. Litman. 2001. Extraordinary variation in a diversified family of immune-type receptor genes. Proc Natl Acad Sci U S A. 98: 13832-13837. [MANUSCRIPT]
Yoder, J.A. 2004. Investigating the function, morphology and genetics of cytotoxic cells in bony fish. Comp. Biochem. Physiol. C. 138: 271-280. [ABSTRACT]
Yoder JA, Litman RT, Mueller MG, Desai S, Dobrinski KP, Montgomery JS, Buzzeo MP, Ota T, Amemiya CT, Trede NS, Wei S, Djeu JY, Humphray S, Jekosch K, Hernandez Prada JA, Ostrov DA, Litman GW. 2004. Resolution of the novel immune-type receptor gene cluster in zebrafish. Proc Natl Acad Sci U S A. 101:15706-15711. [MANUSCRIPT]
P.G. Panagos, K.P. Dobrinski, X. Chen, A.W. Grant, D. Traver, J.Y. Djeu, S. Wei, J.A. Yoder. 2006. Immune-related, lectin-like receptors are differentially expressed in the myeloid and lymphoid lineages of zebrafish. Immunogenetics. 58: 31-40. [ABSTRACT]
A. Deiters, J.A. Yoder. 2006. Conditional Transgene and Gene Targeting Methodologies in Zebrafish. Zebrafish. 3: 415-429 [MANUSCRIPT]
Yoder, J.A., T.M. Orcutt, D. Traver and G.W. Litman. 2007. Structural characteristics of zebrafish orthologs of adaptor molecules that associate with transmembrane immune receptors. Gene. 401: 154-164. [ABSTRACT]
Wei, S., J-m Zhou, X. Chen, R.N. Shah, J. Liu, T.M. Orcutt, D. Traver, J.Y. Djeu, G.W. Litman and J.A. Yoder. 2007. The zebrafish activating immune receptor Nitr9 signals via Dap12. Immunogenetics. 59: 813-821.[ABSTRACT]
Yoder, J.A., J.P. Cannon, R.T. Litman, C. Murphy, J.L. Freeman and G.W. Litman. 2008. Evidence for a transposition event in a second NITR gene cluster in zebrafish. Immunogenetics. 60: 257-265. [ABSTRACT]
Desai, S., A.K. Heffelfinger, T.M. Orcutt, G.W. Litman, J.A. Yoder. 2008. The medaka novel immune-type receptor (NITR) gene clusters reveal an extraordinary degree of divergence in variable domains. BMC Evol. Biol. 8: 177. [MANUSCRIPT]
Young, D.D., H. Lusic, M.O. Lively, J. A. Yoder and A. Deiters. 2008. Gene silencing in mammalian cells with light-activated antisense agents. ChemBioChem. 9:2937-2940. ABSTRACT
Yoder, J.A. 2009. Form, function and phylogenetics of NITRs in bony fish . Dev. Comp. Immunol. 33: 135-144. ABSTRACT
Young, D.D., R.A. Garner, J. A. Yoder and A. Deiters. 2009. Light-activation of gene function in mammalian cells via ribozymes. Chem. Commun. 5: 568-570. ABSTRACT
D.D. Jima, R.N. Shah, T.M. Orcutt, D. Joshi, J.M. Law, G.W. Litman, N.S. Trede and J.A. Yoder. 2009. Enhanced transcription of complement and coagulation genes in the absence of adaptive immunity. Mol. Immunol. 46: 1505-1516. ABSTRACT
J.A. Yoder, P.M. Turner, P.D. Wright, V. Wittamer, J.Y. Bertrand, D. Traver, G.W. Litman. 2010. Developmental and tissue-specific expression of NITRs. Immunogenetics 62: 117-122 [MANUSCRIPT]
Deiters, A., R.A. Garner RA, H. Lusic, J.M. Govan, M. Dush, N.M. Nascone-Yoder, and J.A. Yoder. 2010. Photocaged morpholino oligomers for the light-regulation of gene function in zebrafish and Xenopus embryos. J. Am. Chem. Soc. 132:15644-50. PMID: 20961123
Yoder, J.A. and G.W. Litman. 2011. The phylogenetic origins of natural killer receptors and recognition: relationships, possibilities and realities. Immunogenetics. 63:123-141. PMID: 21191578
Poem Turner, Research Associate, Poem_Turner@ncsu.edu
Laila Farzana, Post-doc, firstname.lastname@example.org
Iván Rodriguez, Post-doc, email@example.com
Hayley Dirscherl, Biomedical Engineering Graduate Student, firstname.lastname@example.org