Regulatory T (Treg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumor immunity. Conversely, Treg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties, can promote autoimmunity and/or facilitate more effective tumor immunity. A comprehensive understanding...
Herpes simplex virus (HSV) is a ubiquitous human pathogen capable of causing debilitating diseases such as herpes stromal keratitis (HSK) and herpes simplex encephalitis (HSE). Although HSV infection initiates disease pathogenesis, the resulting clinical manifestations are attributed to immunopathological events that occur following viral clearance. To elucidate the molecular mechanisms...
Natural Killer (NK) cell dysfunction is associated with poorer clinical outcome in cancer patients. What regulates NK cell dysfunction in tumor microenvironment is not well understood. NKG2D/NKG2DL pathway is very well recognized as an effective immune axis in tumor immunosurveillance. Abundant evidence from experimental preclinical animal models as well as...
Cytokines made by macrophages play a critical role in determining the course of Legionella pneumophila infection. Prior, murine-based modeling indicated that the cytokine response initiated upon recognition of L. pneumophila involves a subset of Toll-like receptors, namely TLR2, TLR5, and TLR9. Using shRNA/siRNA knockdowns and subsequently CRISPR/Cas9 knockouts (KO), I...
Newborns are particularly susceptible to severe forms of herpes simplex virus type I (HSV-1) infection including encephalitis and multisystemic disseminated disease. The underlying age-dependent differences in the immune response that explain this increased susceptibility relative to the adult population remain largely understudied. Evidence from animal studies and genetic studies in...
Transplantation is necessary and often the only viable treatment for many forms of end stage organ failure. While advances in immunosuppressive therapies have facilitated largely blocking acute rejection, 5-10 year post-transplant attrition rates have not significantly improved in the past 30 years. The predominant antigen facilitating the alloimmune response is...
Staphylococcus aureus (SA) is a leading cause of healthcare-associated and community-acquired infection in the United States. Despite the canonical thinking that antibodies and B cells are the main drivers of protection against extracellular pathogens, T cells are now recognized as critical players in protection against SA in multiple routes of...
When properly regulated, inflammation leads to the recruitment and activation of circulating leukocytes to maintain and restore tissue homeostasis. Although this process is critical for successful wound healing and the elimination of pathogens and infections, misdirected inflammation can exacerbate pathology and cause substantial morbidity and mortality. Inflammation a fundamental process...
This dissertation focuses on the development of quantitative approaches for characterizing endogenous signaling pathways and designing new pathways in mammalian cells. I demonstrate how mathematical descriptions that are formulated to explain gene expression patterns can also serve as a powerful springboard for deeper analyses into the properties and functions of...
Bacteria often coordinate virulence factors to fine-tune the host response during infection. These coordinated events can include toxins counteracting or amplifying effects of another toxin or though regulating the stability of virulence factors to remove their function once it is no longer needed. Multifunctional autoprocessing repeats-in toxin (MARTX) toxins are...