The immune system is the most complex genetic system described to date. Using a number of different approaches, studies originated in the laboratory of Gary Litman, Ph.D. (emeritus) helped redefine our understanding of the phylogeny of immune response genes. Currently led by Larry Dishaw, Ph.D, the molecular genetics laboratory is studying how diverse components of the immune system maintain normal and healthy interactions with microbial communities that colonize various surfaces of the body, i.e., the microbiome. Since mucosal surfaces are key interfaces between host and the environment, simple disruptions can contribute to instabilities such as loss of homeostasis, inflammation, allergy, autoimmune-like conditions, etc.
Over the years, the molecular genetics laboratory has utilized diverse model systems to identify novel families of immune receptors possessing distinct structural and regulatory features. These innate immune molecules, in some cases, also appear to utilize alternative signaling pathways for mediating immune function and as such have enhanced our understanding of integration of regulatory networks that factor into host protection.
A recently utilized model, for example, was the zebrafish, which afforded unique experimental advantages. Zebrafish was found to possess two major (and novel) families of immune receptor genes that encode variable region domains in addition to those that function in the mammalian-like adaptive immune system of this species. Although one of the gene families, novel immune-type receptors (NITRs), appears to encode natural killer (NK) receptors, the role of the other multigene family, diverse immunoglobulin domain-containing proteins (DICPs), presently is not understood. DICPs bind lipid ligands and lack a homolog outside of bony fish. Various in vitro and in vivo approaches were used to determine how these extraordinarily diverse genes function in innate immunity; efforts revealed lipid binding as a basic mechanism in modulating innate immune function in the CD300/TREM gene families in higher vertebrate models.
Molecular Genetics Laboratory faculty include: