Research Interests

Multigene families of Ig domain-containing innate immune receptors

The genomes of teleost fish, including zebrafish, possess many multigene families that encode cell surface receptors involved in innate immunity. The majority of these receptors transduce either inhibitory or activating signals across the cell membrane and utilize different types of extracellular Ig domains for ligand recognition that, unlike Ig domains involved in adaptive immunity, do not undergo somatic recombination. Several of these innate immune receptors appear restricted to the Osteichthyes class of fish. The immunological needs of these fish species, which are egg-laying with ex-utero embryonic development, may be related with the emergence and expansion of these gene families. These multigene families include novel immune-type receptors (NITRs), which have been proposed as NK receptors, diverse immunoglobulin domain containing proteins (DICPs) and polymeric immunoglobulin receptor (pIgR) like (PIGRL) proteins. Select DICP and PIGRL Ig domains proteins bind different phospholipids, an ability shared with the mammalian CD300 and TREM family of receptors. In addition, some of these gene families are located in areas of the zebrafish genome that exhibit copy number variation (CNVs). The presence of CNVs in immunological genes has been related with either resistance or susceptibility to different infections and autoimmune diseases.
It is evident that many more multigene receptor families remain to be discovered and much work is left to fully understand these families. Research into these gene families will provide a better understanding on alternative pathways of innate immunity and cross species analyses.



There are more than 80,000 chemicals in production globally; however, toxicity data for most of these chemicals are limited for both humans and environmental species. Zebrafish have quickly become a laboratory workhorse in the toxicology field to help evaluate and prioritize potentially toxic chemicals. Zebrafish possess all the major hematopoietic lineages as mammals and their embryos provide a whole animal model for studying innate immunity with no interference from adaptive immunity. By 72 hr post fertilization (hpf), embryos can clear infections with fully functional macrophages and neutrophils independent of B and T cells which are not functional until ~3 weeks after fertilization. Their ex-utero development and small size renders zebrafish embryos ideal for medium- to high-throughput screens. In addition, orthologs of ~70% of all human protein coding genes are present in the zebrafish making them a strong model for human immmunogenetics.  We employ the zebrafish embryo model to study the effects of environmental chemicals on innate immunity in a biologically relevant manner. Using the zebrafish as a whole animal screening tool, we can identify compounds for follow-up studies in human cells. To date, we have screened more than 20 chemicals in immunotoxicity assays to test whether various classes of compounds are able to suppress or stimulate the innate immune system. Most recently, our lab has begun to explore the per- and polyfluoroalkyl substances (PFASs). These anthropogenic compounds are an emerging class of toxicants used in the production of nonstick coatings, food wrappers, and fire-fighting foams. Their unique chemistry has made them highly persistent within the environment and living organisms, with adverse effects having been reported in the cardiovascular, nervous, and adaptive immune systems. We hope to expand the field to find the harmful effects of these compounds on the innate immune system using novel in vivo and in vitro approaches. This research will allow for better understanding of how environmental toxicants contribute to human health and disease with hopes to increase awareness and regulations involving these chemicals.

Conserved innate immune response genes

Although humans and zebrafish have several hundred million years of evolutionary divergence between them, they still share many conserved, homologous genes. The immense evolutionary pressure to maintain the homology among these conserved genes suggests that they carry vital functions in the vertebrate system. Deciphering these functions in the zebrafish model carries the potential of translational applications including identifying new therapeutic targets in human and animal disease. With this in mind, one focus of the lab is to identify and understand novel immune related genes that are maintained across multiple species. Using the zebrafish model and gene expression analyses, we have defined a whole-organism innate immune response transcriptome and identified multiple genes that are transcriptionally up-regulated in zebrafish larvae after immune stimulation with bacterial and viral mimics. Ongoing investigation and characterization of these novel genes is an exciting area of interest that garners the potential of advancing our understanding of the innate immune system as well as identification of some translational targets of future pharmaceuticals.


Zebrafish MHC Class I

The major histocompatibility complex class I (MHCI) genes play a central role in vertebrate immunity. Classical MHCI proteins are expressed on nearly all cells and present peptide antigens to cytotoxic T-cells in order to initiate an immune response. In addition, the presence of MHCI molecules on the cell surface provides a protective mark of “self” to surveillant cytotoxic (natural killer) cells. While zebrafish are known to express orthologs of mammalian MHCI, the characterization of the genetic and functional diversity of zebrafish MHCI genes is incomplete. Zebrafish MHCI genes are classified into three different lineages: the “U” genes on chromosome 19, the “Z” genes on chromosomes 1 and 3, and the “L” genes on chromosomes 3, 8, and 25. The U genes possess features characteristic of classical MHCI function, the L genes exhibit features of non-classical MHCI function, and the Z genes display features of both classical and non-classical MHCI. With the availability of individual animals from diverse genetic backgrounds, both laboratory-raised and wild-caught, zebrafish are a great model for investigating the intraspecific diversity of this highly polymorphic and rapidly evolving multi-gene family. Zebrafish studies are being partnered with cell-based studies to determine the functional diversity of the different MHCI lineages in zebrafish.