Research projects

  • Regulation of Th9 cell responses through lipid metabolism pathways (ongoing). Th9 cells are a CD4 T cell subset that produces interleukin-9 (IL-9), a cytokine implicated in allergies, autoimmunity and cancer. Defining the factors regulating its expression are essential for fully understanding its roles in immunity and disease. Recent studies from our lab and others have expanded our understanding of Th9 cell function beyond cytokine and transcription factor pathways. Notably, fatty acid metabolism has emerged as a key regulator of IL-9 production. Our findings demonstrated that acetyl-CoA carboxylase 1 (ACC1) suppresses IL-9 through fatty acid synthesis, while the PPAR-g agonist rosiglitazone suppresses IL-9 independently of glycolysis. Our work is aimed at defining the mechanisms of how ACC1 and PPAR-g suppress IL-9 in human CD4 T cells. Overall, targeting these pathways may offer new therapeutic strategies for IL-9-driven diseases. Frontiers | Regulation of human Th9 cell differentiation by lipid modulators targeting PPAR-γ and acetyl-CoA-carboxylase 1
  • Exploring the role of GPR68 in head and neck carcinogenesis (completed). Squamous cell carcinoma of ( the head and neck (SCCHN) is one of the deadliest cancers with more than 14,000 expected deaths, and greater than 65,000 new cases in the United States (US) in 2020. Former and active smokers as well as users of smokeless tobacco products are at the highest risk of developing this invasive cancer. Mortality from SCCHN could be reduced through the identification of new molecular targets associated with SCCHN carcinogenesis. GPR68, also known as ovarian cancer G protein-coupled receptor 1 (OGR1), is a pH-sensing G-protein-coupled receptor (GPCR) that responds to extracellular acidity, a defining hallmark of the tumor microenvironment (TME). GPR68 is expressed in several tissues such as esophagus, stomach, intestine, bone, endothelium, immune system, lungs and cancer. Emerging evidence has revealed that GPR68 may play crucial roles in tumorigenesis, tumor growth, and metastasis. This project explored a novel role for GPR68 in SCCHN carcinogenesis. https://www.nature.com/articles/s41598-023-27546-y
  • MyD88-dependent regulation of intestinal epithelial cells by dietary fat. Obesity is linked to metabolic syndrome and changes in intestinal bacteria.  Intestinal epithelial cells (IECs) separate the luminal and internal compartments of the gastrointestinal (GI) tract, and are the first point of contact with gut bacteria.  Disruptions in the epithelial barrier contribute to inflammatory disorders from microbial translocation.  Although high fat diets (HFD) are known to increase GI permeability and alter the composition of intestinal microbes, the effects of HFD on IEC function are not fully characterized.  Microbial products stimulate toll-like receptors (TLRs) on immune cells, initiating an inflammatory signaling cascade mediated by an adaptor named MyD88.  This study is testing the hypothesis that dietary fat regulates IEC gene expression in a MyD88-dependent manner.