Antimicrobial resistance development and therapy, Fungal pathogenesis, Candida biofilm pathogenesis and resistance, preclinical anti-infective drug development
Aging; endocrinology; development; degenerative diseases of the central nervous system
Aging; Alzheimer’s disease, Neurobiology of Disease, Behavior and Cognition
The primary focus of the work in my lab centers on mucosal diseases in the airways. Mucosal surfaces, such as the airways, are under constant attack by bacterial and viral pathogens. The first line of protection against these pathogens is mediated by a “nonspecific” immune response, termed innate immunity. Innate immunity response is an inflammatory response by the recognition of molecular patterns indicating the presence of replicating organisms. These molecular patterns are recognized by pattern recognition receptors on the surface of epithelial cells and others. Once triggered, pattern recognition receptors produce the expression of inflammatory and anti-viral genes by the epithelium. These proteins result in shaping the adaptive immune response important in specific immunity.
Our studies have demonstrated the central role of a transcription factor, termed NFB, and the mechanism how it activates inflammatory gene expression. Our work shows that NFB activates a rapid, regulated gene expression mechanism termed “transcriptional elongation” to mediate innate response. Not only does this pathway provide acute response to new viral infections, our studies have shown that the NFB pathway controls cellular reprogramming, cell-state transition and remodeling/fibrosis.
Breast cancer and drug development
I am a gastrointestinal oncologist at the University of Wisconsin Carbone Cancer Center (UWCCC) and the William S Middleton Veterans Hospital. I have a subspecialty focus in the treatment of colon, rectal and anal cancers. My research aims to fundamentally change the way in which we treat gastrointestinal cancers to a more personalized approach.
Host-pathogen interactions; the role of macrophages in immunity to intracellular pathogens; innate immune responses like cytokine production & microbial killing amplified by extracellular nucleotide receptor known as P2X7 (significant functional diversity for this receptor exists between cell types & human subjects); role of P2X7 as candidate gene modulating the human innate immune responses of macrophages & airway epithelial cells to Chlamydia pneumoniae, contribution of responses of asthma
The cellular and molecular mechanisms of fibrogenesis in native and transplant kidney disease
Tumors are often heterogeneous with respect to many features. My research focuses on identifying sources of heterogeneity and determining how such heterogeneity impacts prevention and treatment. Novel concepts are being tested with a unique experimental platform consisting of recently developed animal models and state-of-the-art imaging. The results could potentially shift current paradigms in cancer biology.