Center Affiliation and Expertise: Systemic and Redox Toxicology
Our research has developed in two main areas: 1) How viruses infect and disseminate in skin; 2) How microbial and environmental factors play a role in the development of metabolic syndrome. Our prior research addressed how human cells senesce, leading to aging, and how they become immortal, leading to cancer, with a particular interest in on how human papillomaviruses transform cells. Our expertise in cell immortalization and cell culture techniques has allowed us develop 3D cell culture models that recapitulate human tissue for our research.
1) How viruses infect and disseminate in skin. Collaborative studies were recently initiated with Wendy Maury’s lab to examine how Ebola virus (EBOV) infects and transmits through human skin. We found that EBOV can infect and replicate in different skin cell populations. We are currently working to understand the course of infection in skin, what specific receptors are being utilized by EBOV in skin cells, and what role skin infection plays in transmission and pathogenesis.
2) How microbial and environmental factors play a role in the development of metabolic syndrome. Our success with immortalizing human preadipocytes (pre-fat) cells has led to studies on how environmental and bacterial toxins cause or exacerbate type II diabetes through effects on fat tissue. We found that dioxin-like polychlorinated biphenyls (PCBs), which are persistent organic pollutants, can disrupt adipogenesis (i.e. the development of functional fat cells) through activation of the aryl hydrocarbon receptor (AhR). This causes a proinflammatory response and inhibits master regulatory genes involved in adipogenesis. Endogenous microbial-derived tryptophan metabolites are also able to activate AhR. Studies are underway to determine the mechanism by which AhR activation disrupts adipogenesis and to develop 3D cultures and in vivo genetic models to assess the role of AhR in the development of metabolic syndrome.
Complete List of Published Works https://www.ncbi.nlm.nih.gov/pubmed/?term=klingelhutz+aj