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Investigating Immune Response

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  • Title: Assistant Professor, North Carolina State University
  • Education: PhD, Harvard University, 1998
  • Recommended by: Barbara Sherry

As a self-described evolutionary immunologist, North Carolina State University’s Jeff Yoder spends a lot of time tracking immune response in zebrafish. Part of his research focuses on identifying and characterizing novel immune type receptors in bony fish. A second focus of his research is using zebrafish larvae to study innate immunity — at this stage of development, zebrafish do not yet have a functioning adaptive immune system, so it’s possible to probe innate immunity and thereby get at the genes that give rise to the ability to produce antibodies. “I’m using a microarray approach to identify novel immune response genes,” Yoder says, “and then ultimately, we’ll be partnering the experimental strengths of both zebrafish and mouse for future functional studies.”

In one approach, he and his team feed the zebrafish lipopolysaccharide, which induces a whole organism immune response. They then measure differential gene expression with microarrays to pinpoint immune response genes of interest. They’re finding both immune and stress response genes, which is the result of dosing the whole animal. “When a whole organism sees these things, it’s not just the immune cells,” Yoder says. “And so now we’re working on ways of filtering through all that and prioritizing the genes of interest.”

Yoder became interested in using zebrafish as a model for immunity as a postdoc in Gary Litman’s lab at the University of South Florida. Prior to that, he was in Tim Bestor’s Harvard lab, where he got his PhD in cell and developmental biology.

A big part of Yoder’s approach involves seeking out genes that don’t have much coverage yet on PubMed. “I’m trying to create what I like to call my ‘balance portfolio’ of genes, where I’m trying to include early and late response genes after exposure to [lipopolysaccharide], trying to include genes that appear to be transcription factor-related, proteins that appear to be membrane-bound, proteins that appear to be secreted.”

What really drives Yoder’s work is a desire to blaze his own path, meaning discovering novel genes. “I sort of have this history of working on novel genes,” he says. “When you start working on a novel gene or gene family that has not yet been reported or characterized, then anything and everything is possible for an experimental approach. And that’s what I like.”

Looking ahead

One of the biggest challenges for the field is the paucity of molecular tools available for monoclonal antibodies. However, Yoder says, the zebrafish community has created some clever workarounds, specifically by creating various transgenic strains in which specific cells light up with GFP. As for Yoder’s future, he’ll be working on finding new genes, and hopefully one or a few will become the foundation for the rest of his research career. In the meantime, the best technology to speed up his research would be “affordable ways to define the entire transcriptional profile within a single cell.”

Publications of note

Last year, Yoder published a paper in Science that identified the mammalian DNMT2 to be a RNA methyltransferase, contrary to conventional belief that it was a DNA methyltransferase (“Methylation of tRNAAsp by the DNA Methyltrans-ferase Homolog Dnmt2.”).

And the Nobel goes to …

If he won the Nobel Prize, Yoder says, “It would be great if we could develop engineered NK cells that would be designed on a patient-to-patient basis, so that you could use these engineered cells to target patient specific tumor cells,” he says. “And then you could theoretically program the NK cells based on the tumor type. I don’t know how you would do this, but I think that would be cool.”

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