The overarching theme of our research is improving understanding of the evolution of immunogenetic variation and its impact on human health and disease. In practice, our work emphasizes the rigorous application of population genetics theory and methods with scrupulous attention to consistent and standardized management of diverse data sets. A primary focus is analysis of the highly polymorphic Human Leukocyte Antigen (HLA) loci for autoimmune disease association, transplant, population genetics and evolutionary studies. We also study a related gene system, the Killer-cell Immunoglobulin-like Receptor (KIR) loci. Because these receptors interact with HLA to mediate activity of natural killer cells, their variation alone, or in tandem with HLA, has a prominent role in many disease processes and the evolution of human immunity. 

We integrate our work in immunogenetics with new and ongoing research within the Department of Neurology, to advance efforts to elucidate the genetic basis of underlying immune dysregulation in neurological diseases such as multiple sclerosis (MS) and Parkinson’s Disease. In addition to basic research in immune response genetics, our work developing data management and analysis standards supports data-intensive projects within the MS researchgroup, including projects related to data integration for multicenter cohorts and tools for precision medicine. 

HLA and KIR associations in neurological disease

The overall goal of this project is to establish and refine the association of genetic polymorphism of the HLA and KIR loci with neurological disease. 

Mapping the intersection between self-identification and genetics

In order to improve analysis for disease association studies, matching for transplant, and data collection for population studies, our group has been investigating and assessing alternative approaches to measuring self-identified race and ethnicity, by direct comparison of ancestry survey responses with genetic markers in a very large (N>100,000) cohort. 

Immunogenetics of emerging pathogens

In collaboration with the Virgin Islands Department of Health and the Centers for Disease Control, our lab is examining the the role of immunogenetic variation in vulnerability to infection and long-term sequelae from Chikungunya virus. 

Integrated Immunogenetic Data Exchange, Storage and Analysis 

Our lab is developing bespoke data management and analysis software for immunogenetic research and clinical practice. 

Binding of HLA to human metabolites in multiple sclerosis

In this study, we hypothesize that naturally occurring small molecules may bind the MS susceptibility allele DRB1*15:01, resulting in conformational changes or causing a register shift to the bound peptide and thus altering T-cell recognition and responsiveness.

Other current collaborations

We provide analytical support for projects examining HLA disease associations and the populations genetics of the KIR loci (Stanford University), as well as fine-mapping variants adjacent to the HLA loci that impact hematopoietic stem cell transplant outcome (Fred Hutchinson Cancer Research Center). Dr. Hollenbach is also a longtime collaborator with the National Marrow Donor Program bioinformatics research group, with several ongoing research projects.