Jason L. Kubinak, Ph.D.
Assistant Professor
Postdoctoral Training
2011-2016, University of Utah School of Medicine, Department of Pathology

Educational Background:
B.S. - Cook College, Rutgers University, NJ
M.S. - James Cook University, QLD, AUS
Ph.D. - University of Utah, UT

Contact Information:
Phone: (803) 216-3421
Email: Jason.Kubinak@uscmed.sc.edu

Research Focus

I am a broadly trained immunologist with research interests that lie at the intersection of multiple fields including evolutionary biology, ecology, immunology, and microbiology. Broadly, my laboratory is interested in defining the molecular mechanisms that facilitate crosstalk between B cells and members of the symbiotic community of microbes that reside on the gut mucosa (the gut microbiota). Members of the gut microbiota can influence the quality and quantity of the secretory antibody response that develops in an individual, and the secretory antibody response can regulate species composition and the functional capacity of this microbial community. Understanding the molecular mechanisms governing this interaction will yield important insights into the nature of antigen recognition and epitope selection in the gut that could aid in the development of more efficacious oral vaccines. My doctoral work focused on evolutionary concepts regarding the nature of selection maintaining the extreme allelic diversity observed at MHCII loci in humans (e.g. there are over 1000 functional alleles maintained at the DR locus in humans alone). My postdoctoral work focused on characterizing the role of innate (TLR) and adaptive (MHCII) immune recognition pathways in the development of anti-commensal immunoglobulin A (IgA) antibody responses in the gut. As a new member of the PMI Department, my current work is focused in three main areas that I briefly highlight below:

  • Defining how innate and adaptive signaling pathways influence gut antibody repertoire development: Vertebrates are unique in their ability to generate antigen-specific immune responses and form long-lasting immunological memory. Toll-like receptors (TLRs) and classical major histocompatibility complex (MHC) molecules are central to both of these phenomena because they coordinate a process of epitope selection that focuses the immune response towards certain antigens over others. Current research in my laboratory is focused on understanding how these two immune recognition pathways influence antibody repertoire development in the gut, and how this in turn influences antibody targeting of the microbiota and susceptibility to infection of the gut as well as systemic compartment. This work is currently funded by a K22 Career Development Award (K22AI123481).
  • Understanding the impact of histocompatibility gene polymorphisms on anti-commensal antibody responses and their effect on host physiology: Classical major histocompatibility complex class II (MHCII) genes encode cell surface molecules that bind protein antigens and facilitate crosstalk between B and T cells. Interestingly, these are also some of the most polymorphic genes within vertebrates. For the past ten years I have been developing an expertise in MHC congenic mouse models, which are essential tools for assessing the health consequences of MHCII variation in humans (e.g. the two H2 genes in mice, IE and IA, are homologous by decent to the human HLA-DR and HLA-DQ genes). MHC allele variants have been identified as risk factors for almost all known infectious, inflammatory, and autoimmune diseases in humans, and it is generally assumed that this is due to the ability of MHC molecules to skew immune responses among individuals. Research in my lab seeks to characterize the mechanism by which MHCII gene polymorphisms skew antibody responses in the gut and how this influences host physiology. Gut antibody responses are important for promoting benign symbiotic associations between vertebrate hosts and the microbial species that inhabit the gut (the microbiota), but can also protect against invading pathogens through the production of cross-reactive antibody specificities. This work seeks to characterize the molecular mechanism linking MHCII polymorphism with antibody deficiencies in humans, and to provide deeper insight into the role anti-commensal antibody responses play in protecting from systemic disease.
  • Exploring the link between primary antibody deficiency (PAD) and inflammation caused by host-microbiome dysbiosis: Primary immunodeficiency diseases are heritable disorders of immune system function that most commonly manifest as a PAD. Infectious and non-infectious enteropathies are commonly observed in PAD patients, suggesting that aberrant antibody responses may perturb gut homeostasis and increase risk of pathologic interactions (i.e. dysbiosis) with commensal microbes. Work with mouse models strongly support this, and epidemiological data has linked IgA deficiency with other diseases now understood to be associated with an underlying alteration to gut microbial communities like inflammatory bowel disease and celiac disease. A third area of ongoing research in the lab seeks to understand how alterations to microbiome form (species composition) and function (gene content, transcriptome) is influenced by IgA deficiency, and how this in turn influences susceptibility to acute and chronic diseases associated with the resulting inflammation. This is in an attempt to 1) characterize novel disease risks associated with IgA deficiency and 2) identify novel therapeutic treatments that alleviate gut inflammation that results from antibody deficiency.