Primary Faculty

Lauren Zenewicz, PhD

Lauren Zenewicz, PhD

Assistant Professor


Ph.D.: 2004, University of Pennsylvania, Philadelphia, PA

Post-doctoral Fellowship:

Yale University, New Haven, CT

Research Interests:

Cytokines, mucosal immunology, inflammation, infection, cancer, cell signaling, immunometabolism



Contact Information:

Office: BMSB 1034


Research Interests:

My broad research goals are to dissect the complex interactions between the immune system, mucosal tissues and the environment, in both health and disease. Using complementary in vitro and in vivo approaches, we are examining the pathways that regulate activation and cytokine production in innate and adaptive lymphocytes in the gastrointestinal tract. Current research in my laboratory is focused on the studying the immunology of Clostridioides difficile infection and the biology of innate immune cells, with an emphasis on immunometabolism.


Interleukin-22 (IL-22) is a critical cytokine in modulating tissue responses during inflammation. IL-22 is upregulated in many chronic inflammatory diseases, including inflammatory bowel disease (IBD), making IL-22 biology a potentially rewarding therapeutic target. However, this is complicated by the dual-natured role of IL-22 in inflammation as the cytokine can be protective or inflammatory depending on the disease model. There is still much we do not know about the environmental, cellular and molecular factors that regulate the production and function of this cytokine. A better understanding of IL-22 biology will allow us to develop new or improved therapeutics for treating chronic inflammatory and infectious diseases. Our research focuses on the environmental and molecular factors that regulate production of IL-22 from its two major cellular sources, CD4 T cells and group 3 innate lymphocytes (ILC3s).


Oxygen is an important fuel for metabolism of immune cells. In CD4 T cells, we have shown that IL-22 levels are increased in low oxygen, an environmental cue that often accompanies inflammation (Budda et al. Journal of Immunology. 2016). This upregulation is dependent on the transcription factor hypoxia inducible factor-1a (HIF-1a). We have also shown that a negative regulator of HIF-1a, VHL, is a potent controller of IL-22 expressing T cells and affects their cellular metabolism (Chitrakar et al. Journal of Immunology. 2020). We have also examined the effects of low oxygen on how epithelial cells respond to IL-22 and found that hypoxia downregulates epithelial cell responses to IL-22 stimulation (Budda et al. Immunology & Cell Biology. 2017). Our research suggests that IL-22 biology is a complicated integration of signals both in the production of the cytokine and how the target cells respond to the cytokine.


Innate lymphocytes are a broad class of lymphocytes that lack diverse, rearranged antigen-specific receptors. Group 3 innate lymphocytes (ILC3s) are rare immune cells, found primarily in mucosal tissues and a major producer of IL-22. Environmental signals are central for ILC3 activation and the most potent inducers of IL-22 production are IL-23 and IL-1b. We have shown that other environmental signals, including bacterial toxins and man-made glucocorticoids used in IBD therapy, downmodulate ILC3 production of IL-22 (Seshadri et al. PLOS Pathogens. 2017, Seshadri et al. Journal of Immunology. 2018 and Sah et al. Cytokine. 2022). Mechanistically, we identified previously unknown molecular circuits involving MAPK, cAMP and NF-kB signaling that regulate IL-22 production in ILC3s. These data have implications on strategies to modulate either the function of ILC3 or the biological activity of IL-22 during infectious disease or chronic inflammation.


C. difficile is the most common hospital acquired bacterial infection and patients often have relapsing disease, suggesting the host immune response is limited during infection. We lack fully effective treatments for this mucosal pathogen and there is critical need to better understand how C. difficile interacts with our immune system. At the interface between the host and the environment, mucosal barriers are the first line of defense against invasive pathogens such as C. difficile. Recent studies in mice have revealed a critical role for ILC3s and IL-22 in mucosal barrier maintenance, including C. difficile infection. We have recently identified a novel mechanism of ILC3 activation directly by the major virulence factor C. difficile toxin B (TcdB) (Pope et al. Infection and Immunity. 2022) and are currently investigating how TcdB modulates the host immune response. Enhancing innate immunity, especially by targeting cytokine biology, has great potential for reducing incidence and severity of initial and recurrent C. difficile infections.

Current Lab Personnel:

Tarosha Salpadoru, Ph.D., Post-doctoral Fellow

Selected Publications:

For a complete list of over 40 publications, see PubMed: