Rajat Madan , MD,PhD
Associate Professor of Clinical
Medical Sciences Building
Room 6105C
231 Albert Sabin Way
Cincinnati, Ohio 45267
Phone 513-558-4704
Fax 513-558-2089
Email rajat.madan@uc.edu
Education
Bachelor of Medicine, Bachelor or Surgery (M.B.B.S): JLN Medical College 2000
Doctoral Degree: University of Cincinnati 2009 (Molecular and Developmental Biology and Molecular Immunology)
Residency: The Christ Hospital 2011 (Internal Medicine)
Fellowship: University of Virginia 2014 (Infectious Diseases)
Certifications
American Board of Internal Medicine (Infectious Disease) (Certification Date: 10-28-2014 )
American Board of Internal Medicine (Certification Date: 08-12-2011 ) - (Recertification Date: to 01-01-2023 )
Clinical Interests
Infectious Disease
Specialities
Infectious Diseases
Internal Medicine
Research and Practice Interests
The overall goal of our studies is to define novel, host targets 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. However, microbes have evolved for billions of years and have mechanisms that allow them to escape such strategies as evidenced by high degree of antibiotic resistance. Further, it is 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. Therefore, our laboratory focuses on studying the role of host factors that regulate the pathogenesis of infectious diseases. The long-term goal of our work is to discover novel targets for development of host-targeted therapies for the treatment of infectious disease.
The main focus of our current studies is to define the host genetic and immune mediators that are beneficial and/or harmful after Clostridioides difficile infection (CDI). C. difficile is the #1 cause of healthcare-associated infections in 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, human intestinal enteroids and organoids for our studies.
Research Support
Grant: #K08 AI108801 Investigators:Madan, Rajat 01-01-2015 -07-31-2019 National Institute of Allergy and Infectious Diseases Role of leptin in mucosal protection during Clostridium difficile infection Role:PI $176,057.00 Completed
Grant: #Research Collaboration Agreement Investigators:Madan, Rajat 06-01-2018 -05-31-2019 Cincinnati Children Impact of obesity-associated microbiome and bile acid metabolites in regulating Clostridium difficile lifecycle Role:PI $50,000.00 Completed
Grant: #R01AI158451 Investigators:Madan, Rajat; Weiss, Alison 09-17-2021 -08-31-2026 National Institute of Allergy and Infectious Diseases Regulation of C. difficile colitis by host genetic and immune factors Role:PI 2039928.00 Active Type:Grant Level:National
Grant: #I01BX004630 Investigators:Rajat Madan; Shinsmon Jose; Maggie Powers-Fletcher 07-01-2019 -06-30-2029 Veterans Affairs Medical Center Impact of neutrophil heterogeneity on the pathogenesis of C. difficile infection Role:Principal Investigator 1320000.00 Active Type:Grant Level:National
Publications
Peer Reviewed Publications
Jose, Shinsmon; Madan, Rajat (2016. ) Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections.Anaerobe, , More Information
Madan, Rajat; Demircik, Filiz; Surianarayanan, Sangeetha; Allen, Jessica L; Divanovic, Senad; Trompette, Aurelien; Yogev, Nir; Gu, Yuanyuan; Khodoun, Marat; Hildeman, David; Boespflug, Nicholas; Fogolin, Mariela B; Gröbe, Lothar; Greweling, Marina; Finkelman, Fred D; Cardin, Rhonda; Mohrs, Markus; Müller, Werner; Waisman, Ari; Roers, Axel; Karp, Christopher L (2009. ) Nonredundant roles for B cell-derived IL-10 in immune counter-regulation.Journal of immunology (Baltimore, Md. : 1950), , 183 (4 ) ,2312-20 More Information
Trompette, Aurelien; Divanovic, Senad; Visintin, Alberto; Blanchard, Carine; Hegde, Rashmi S; Madan, Rajat; Thorne, Peter S; Wills-Karp, Marsha; Gioannini, Theresa L; Weiss, Jerry P; Karp, Christopher L (2009. ) Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein.Nature, , 457 (7229 ) ,585-8 More Information
Dragin, Nadine; Shi, Zhanquan; Madan, Rajat; Karp, Christopher L; Sartor, Maureen A; Chen, Chi; Gonzalez, Frank J; Nebert, Daniel W (2008. ) Phenotype of the Cyp1a1/1a2/1b1-/- triple-knockout mouse.Molecular pharmacology, , 73 (6 ) ,1844-56 More Information
Divanovic, Senad; Trompette, Aurelien; Petiniot, Lisa K; Allen, Jessica L; Flick, Leah M; Belkaid, Yasmine; Madan, Rajat; Haky, Jennifer J; Karp, Christopher L (2007. ) Regulation of TLR4 signaling and the host interface with pathogens and danger: the role of RP105.Journal of leukocyte biology, , 82 (2 ) ,265-71 More Information
Tripathi, Pulak; Madan, Rajat; Chougnet, Claire; Divanovic, Senad; Ma, Xiaojing; Wahl, Larry M; Gajewski, Thomas; Karp, Christopher L; Hildeman, David A (2006. ) An adenoviral vector for probing promoter activity in primary immune cells.Journal of immunological methods, , 311 (1-2 ) ,19-30 More Information
Divanovic, Senad; Trompette, Aurelien; Atabani, Sowsan F; Madan, Rajat; Golenbock, Douglas T; Visintin, Alberto; Finberg, Robert W; Tarakhovsky, Alexander; Vogel, Stefanie N; Belkaid, Yasmine; Kurt-Jones, Evelyn A; Karp, Christopher L (2005. ) Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105.Nature immunology, , 6 (6 ) ,571-8 More Information
Divanovic, Senad; Trompette, Aurelien; Atabani, Sowsan F; Madan, Rajat; Golenbock, Douglas T; Visintin, Alberto; Finberg, Robert W; Tarakhovsky, Alexander; Vogel, Stefanie N; Belkaid, Yasmine; Kurt-Jones, Evelyn A; Karp, Christopher L (2005. ) Inhibition of TLR-4/MD-2 signaling by RP105/MD-1.Journal of endotoxin research, , 11 (6 ) ,363-8 More Information
Madan, Rajat; Petri, William A (2015. ) Role of obesity and adipose tissue-derived cytokine leptin during Clostridium difficile infection.Anaerobe, , 34 ,182-6 More Information
Sun, Jie; Madan, Rajat; Karp, Christopher L; Braciale, Thomas J (2009. ) Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10.Nature medicine, , 15 (3 ) ,277-84 More Information
Pot, Caroline; Jin, Hulin; Awasthi, Amit; Liu, Sue Min; Lai, Chen-Yen; Madan, Rajat; Sharpe, Arlene H; Karp, Christopher L; Miaw, Shi-Chuen; Ho, I-Cheng; Kuchroo, Vijay K (2009. ) Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells.Journal of immunology (Baltimore, Md. : 1950), , 183 (2 ) ,797-801 More Information
Murai, Masako; Turovskaya, Olga; Kim, Gisen; Madan, Rajat; Karp, Christopher L; Cheroutre, Hilde; Kronenberg, Mitchell (2009. ) Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis.Nature immunology, , 10 (11 ) ,1178-84 More Information
Denning, Timothy L; Norris, Brian A; Medina-Contreras, Oscar; Manicassamy, Santhakumar; Geem, Duke; Madan, Rajat; Karp, Christopher L; Pulendran, Bali (2011. ) Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization.Journal of immunology (Baltimore, Md. : 1950), , 187 (2 ) ,733-47 More Information
Perona-Wright, Georgia; Mohrs, Katja; Szaba, Frank M; Kummer, Lawrence W; Madan, Rajat; Karp, Christopher L; Johnson, Lawrence L; Smiley, Stephen T; Mohrs, Markus (2009. ) Systemic but not local infections elicit immunosuppressive IL-10 production by natural killer cells.Cell host & microbe, , 6 (6 ) ,503-12 More Information
Naylor, Caitlin; Burgess, Stacey; Madan, Rajat; Buonomo, Erica; Razzaq, Khadija; Ralston, Katherine; Petri, William A (2014. ) Leptin receptor mutation results in defective neutrophil recruitment to the colon during Entamoeba histolytica infection.mBio, , 5 (6 ) , More Information
Madan, Rajat; Guo, Xiaoti; Naylor, Caitlin; Buonomo, Erica L; Mackay, Donald; Noor, Zannatun; Concannon, Patrick; Scully, Kenneth W; Pramoonjago, Patcharin; Kolling, Glynis L; Warren, Cirle A; Duggal, Priya; Petri, William A (2014. ) Role of leptin-mediated colonic inflammation in defense against Clostridium difficile colitis.Infection and immunity, , 82 (1 ) ,341-9 More Information
Buonomo, Erica L; Madan, Rajat; Pramoonjago, Patcharin; Li, Li; Okusa, Mark D; Petri, William A (2013. ) Role of interleukin 23 signaling in Clostridium difficile colitis.The Journal of infectious diseases, , 208 (6 ) ,917-20 More Information
Jarrell, Andrew; Kawsky, Jaclyn; Johnson, Tara; Voss, Sasha; Madan, Rajat; Weitkamp, Tina; Wigle, Patricia (2013. ) An interdisciplinary approach to determine schistosomiasis prevalence and administer praziquantel to school-age children in Tanzania.American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, , 70 (21 ) ,1880-2 More Information
Madan, Rajat; Jr, William A Petri (2012. ) Immune responses to Clostridium difficile infection.Trends in molecular medicine, , 18 (11 ) ,658-66 More Information
Machado, Fabiana S; Esper, Lísia; Dias, Alexandra; Madan, Rajat; Gu, YuanYuan; Hildeman, David; Serhan, Charles N; Karp, Christopher L; Aliberti, Júlio (2008. ) Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6.The Journal of experimental medicine, , 205 (5 ) ,1077-86 More Information
Vargas, Edwin; Apewokin, Senu; Madan, Rajat (2017. ) Role of the leukocyte response in normal and immunocompromised host after Clostridium difficile infection.Anaerobe, , 45 ,101-105 More Information
Jose, Shinsmon; Mukherjee, Anindita; Abhyankar, Mayuresh M; Leng, Lin; Bucala, Richard; Sharma, Divya; Madan, Rajat (2018. ) Neutralization of macrophage migration inhibitory factor improves host survival after Clostridium difficile infection.Anaerobe, , More Information
Alarcon, Pablo C; Damen, Michelle S M A; Madan, Rajat; Deepe, George S; Spearman, Paul; Way, Sing Sing; Divanovic, Senad (2021. ) Adipocyte inflammation and pathogenesis of viral pneumonias: an overlooked contribution.Mucosal immunology, , More Information
Jose, Shinsmon; Mukherjee, Anindita; Horrigan, Olivia; Setchell, Kenneth D R; Zhang, Wujuan; Moreno-Fernandez, Maria E; Andersen, Heidi; Sharma, Divya; Haslam, David B; Divanovic, Senad; Madan, Rajat (2021. ) Obeticholic acid ameliorates severity of Clostridioides difficile infection in high fat diet-induced obese mice.Mucosal immunology, , 14 (2 ) ,500-510 More Information
Horrigan, Olivia; Jose, Shinsmon; Mukherjee, Anindita; Sharma, Divya; Huber, Alexander; Madan, Rajat (2021. ) Leptin Receptor q223r Polymorphism Influences Clostridioides difficile Infection-Induced Neutrophil CXCR2 Expression in an Interleukin-1? Dependent Manner.Frontiers in cellular and infection microbiology, , 11 ,619192 More Information
Markantonis JE, Fallon JT, Madan R, Zahidul MA. (2024. ) Clostridioides difficile infection: diagnosis and treatment challenges.Pathogens, , 13 (2 ) ,118 More Information
Mathew AM, Huber A, Sous RD, Weghorn KN, Powers-Fletcher M, Jose S, Madan R (2024. ) Effect of leptin receptor Q223R polymorphism on Clostridioides difficile infection-induced macrophage migration inhibitory factor production.Journal of Infectious Diseases, ,
More InformationAlam, Md Zahidul; Madan, Rajat (2024. ) Clostridioides difficile Toxins: Host Cell Interactions and Their Role in Disease Pathogenesis.Toxins, , 16 (6 ) , More Information
Mathew, Ann M; Huber, Alexander; Sous, Rowis D; Weghorn, Kristin N; Powers-Fletcher, Margaret V; Jose, Shinsmon; Madan, Rajat (2024. ) Effect of Leptin Receptor Q223R Polymorphism on Clostridioides difficile Infection-Induced Macrophage Migration Inhibitory Factor Production.The Journal of infectious diseases, , More Information
Huber, A; Jose, S; Kassam, A; Weghorn, K N; Powers-Fletcher, Maggie; Sharma, D; Mukherjee, A; Mathew, A; Kulkarni, N; Chandramouli, S; Alder, M N; Madan, R (2023. ) Olfactomedin-4 + neutrophils exacerbate intestinal epithelial damage and worsen host survival after Clostridioides difficile infection.bioRxiv : the preprint server for biology, , More Information
Contact Information
Academic - Medical Sciences Building
Room 6105C
Cincinnati
Ohio, 45267
Phone: 513-558-4704
Fax: 513-558-2089
rajat.madan@uc.edu