Krystal Vail, DVM, PhD, DACVP
Assistant Professor of Pathology and Laboratory Medicine
Biography
Krystal Vail, DVM, PhD, is a veterinary pathologist with a research focus on mechanisms of disease and host-pathogen interactions. Her research to-date has centered on understanding (i) how intracellular bacterial pathogens, such as Mycobacterium tuberculosis, Rhodococcus equi, and Listeria monocytogenes, interact with host innate immune pathways and (ii) how peripheral infections influence neural inflammation and degeneration. Specifically, her work seeks to elucidate the role of the Parkinson’s disease-associated kinase, LRRK2 in innate immunity and how peripheral infections impact the central nervous system. Current projects are centered on LRRK2 and its role in modulating host immunity in response to viral infection using SIV as a model pathogen, and the fragile x messenger ribonucleoprotein (FMRP) and its role in host immunity against bacterial infection.
Education & Affiliations
Research
Uncovering the function of leucine rich repeat kinase 2 in immune pathways
LRRK2 is a large, multifunctional protein kinase with established genetic roles in Parkinson’s disease, inflammatory bowel disease, and susceptibility to mycobacterial infection. Using LRRK2 knockout and mutant mice, primary immune cells, and macrophage cell lines, we revealed a link between peripheral bacterial infections, such as pulmonary M. tuberculosis infections, and inflammatory responses in the brain. Importantly, we found that macrophages deficient in LRRK2 have elevated basal antiviral cytokine expression, associated with an impaired interferon response to infection with mycobacterial pathogens. As part of a multidisciplinary team, we further determined that this altered innate immune response is largely a result of mitochondrial stress leading to mitochondrial DNA leakage into the cytosol and chronic activation of cGAS and the cytosolic DNA sensing pathway. We are currently working on extending our observations of LRRK2’s antiviral phenotype to SIV infection as a model for HIV.
Understanding the contribution of fragile x messenger ribonucleoprotein to the antibacterial immune response
FMRP is an RNA binding protein implicated in host immune function. We are using FMRP KO mouse models and primary macrophages to study FMRP translational modifications of cytokine mRNA during bacterial infection and how translational repression might be regulated.
