Rajat Madan, MD, PhD

The overall goal of my studies is to discover and better define novel targets for development of host-targeted therapies for the treatment of infectious diseases. Ever since the discovery of penicillin, infectious disease therapies have focused on targeting the offending pathogen by using anti-microbial approaches. Microbes, however, have evolved for billions of years and have mechanisms that allow them to escape such strategies as evidenced by a growing high degree of antibiotic resistance. Further, it’s well-known that host factors (e.g., genetic make-up and intensity of host immune responses) are key determinants of clinical outcomes after an infectious insult. My laboratory, therefore, focuses on studying the role of host factors that regulate the pathogenesis of infectious diseases.

My lab’s current studies seek to define the host genetic and immune mediators that are beneficial and/or harmful after Clostridioides difficile infection (CDI). C. difficile is the No. 1 cause of health care-associated infections (HCAIs) in the U.S. and can cause severe diarrhea, fulminant colitis and death. The main ongoing projects in the lab include: (i) examining neutrophil heterogeneity after CDI; (ii) determine the role of neutrophil-derived molecules (e.g., Olfactomedin-4) in regulating tissue injury after CDI; (iii) investigate the role of a common leptin receptor (LEPR) single nucleotide polymorphism (SNP) and downstream signaling from LEPR in regulating CDI-induced neutrophil and cytokine responses; (iv) determine how a pro-inflammatory cytokine, macrophage inhibitory factor (MIF), exaggerates colonic mucosal inflammation, tissue neutrophil recruitment and mortality after CDI; and (v) elucidate the role of altered bile acid metabolism during obesity in regulating CDI severity. We use pre-clinical animal models and samples collected from patients with CDI to determine the role of these host factors in CDI pathogenesis. We use cutting edge techniques including spectral flow cytometry, metagenomics sequencing, single-cell transcriptomics, and human intestinal enteroids and organoids for our studies.