Immunobiology
Pasare Lab

Pasare Lab

The Pasare Lab focuses on understanding the fundamental mechanisms of activation of the innate immune system and its impact on inflammation and adaptive immunity.

The innate immune system relies on specific receptors called pattern recognition receptors to recognize pathogens. Pathogen recognition by the innate immune system leads to inflammation and also activation of adaptive immunity.

The main goal of the lab is to understand the intricate interplay and cross-talk between the innate and adaptive immune systems. In particular, we strive to understand how the innate immune system induces inflammation and its impact on both protective immunity as well as inflammatory disorders.

We have identified several novel proteins and pathways in cells of both innate and adaptive immune systems and use them as handles to address questions relevant to protective immunity, inflammatory disorders and cancer. We use cutting-edge in vitro and in vivo approaches in our studies that are likely to lead to new targets to treat auto-immunity, inflammatory diseases and cancer.

Publications

Meibers, HE; Warrick, KA; VonHandorf, A; Vallez, CN; Kawarizadeh, K; Saha, I; Donmez, O; Jain, VG; Kottyan, LC; Weirauch, MT; et al. Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells. Cell Reports. 2023; 42:113180.

Overcast, GR; Meibers, HE; Eshleman, EM; Saha, I; Waggoner, L; Patel, KN; Jain, VG; Haslam, DB; Alenghat, T; Vandussen, KL; et al. IEC-intrinsic IL-1R signaling holds dual roles in regulating intestinal homeostasis and inflammation. The Journal of Experimental Medicine. 2023; 220:e20212523.

Choi, Y; Lichterman, JN; Coughlin, LA; Poulides, N; Li, W; Del Valle, P; Palmer, SN; Gan, S; Kim, J; Zhan, X; et al. Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity. Science Immunology. 2023; 8:eabo2003.

Shi, T; Malik, A; vom Hofe, AY; Matuschek, L; Mullen, M; Lages, CS; Kudira, R; Singh, R; Zhang, W; Setchell, KD R; et al. Farnesoid X receptor antagonizes macrophage-dependent licensing of effector T lymphocytes and progression of sclerosing cholangitis. Science Translational Medicine. 2022; 14:eabi4354.

Saha, I; Pasare, C. The B cell adapter for PI3K (BCAP) promotes M2 macrophage phenotype and safeguards tumors from immune surveillance. Journal of immunology (Baltimore, Md. : 1950). 2022; 208:61.08.

Kawarizadeh, K; Warrick, K; Pasare, C. BCAP plays a central role in regulating canonical M2 macrophage polarization upon various cell extrinsic signals. Journal of immunology (Baltimore, Md. : 1950). 2022; 208:111.04.

Meibers, H; McDaniel, MM; Jain, A; Chawla, AS; Pasare, C. Effector memory CD4 T cells engage myeloid cells through TNFR and CD40 to induce innate inflammation and autoimmune pathology independent of pattern recognition receptors. Journal of immunology (Baltimore, Md. : 1950). 2022; 208:164.19.

McDaniel, MM; Chawla, AS; Jain, A; Meibers, HE; Saha, I; Gao, Y; Jain, V; Roskin, K; Way, SS; Pasare, C. Effector memory CD4+ T cells induce damaging innate inflammation and autoimmune pathology by engaging CD40 and TNFR on myeloid cells. Science Immunology. 2022; 7:eabk0182.

McDaniel, MM; Meibers, HE; Pasare, C. Innate control of adaptive immunity and adaptive instruction of innate immunity: bi-directional flow of information. Current Opinion in Immunology. 2021; 73:25-33.

Brusilovsky, M; Rochman, M; Rochman, Y; Caldwell, JM; Mack, LE; Felton, JM; Habel, JE; Porollo, A; Pasare, C; Rothenberg, ME. Environmental allergens trigger type 2 inflammation through ripoptosome activation. Nature Immunology. 2021; 22:1316-1326.

Song, R; Gao, Y; Dozmorov, I; Malladi, V; Saha, I; McDaniel, MM; Parameswaran, S; Liang, C; Arana, C; Zhang, B; et al. IRF1 governs the differential interferon-stimulated gene responses in human monocytes and macrophages by regulating chromatin accessibility. Cell Reports. 2021; 34:108891.

Irizarry-Caro, RA; McDaniel, MM; Overcast, GR; Jain, VG; Troutman, TD; Pasare, C. TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation. Proceedings of the National Academy of Sciences of USA. 2020; 117:30628-30638.

Raj, P; Song, R; Zhu, H; Riediger, L; Jun, DJ; Liang, C; Arana, C; Zhang, B; Gao, Y; Wakeland, BE; et al. Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus. Genome Biology: biology for the post-genomic era. 2020; 21:281.

Zhang, J; Tracy, C; Pasare, C; Zeng, J; Kraemer, H. Hypersensitivity of Vps33B mutant flies to non-pathogenic infections is dictated by aberrant activation of p38b MAP kinase. Traffic. 2020; 21:578-589.

Jain, VG; Kong, F; Kallapur, SG; Presicce, P; Senthamaraikannnan, P; Cappelletti, M; Chougnet, CA; Bhattacharyya, S; Pasare, C; Muglia, LJ. IRAK1 Is a Critical Mediator of Inflammation-Induced Preterm Birth. Journal of immunology (Baltimore, Md. : 1950). 2020; 204:2651-2660.

McDaniel, MM; Kottyan, LC; Singh, H; Pasare, C. Suppression of Inflammasome Activation by IRF8 and IRF4 in cDCs Is Critical for T Cell Priming. Cell Reports. 2020; 31:107604.

Overcast, G; Eshleman, E; Alenghat, T; Pasare, C. Epithelial cell intrinsic IL-1R signaling regulates intestinal homeostasis and inflammation. Journal of immunology (Baltimore, Md. : 1950). 2020; 204:235.6.

McDaniel, M; Pasare, C. Suppression of Inflammasome Activation by IRF8 and IRF4 in cDCs is Critical for T cell Priming. Journal of immunology (Baltimore, Md. : 1950). 2020; 204:69.5.

Meibers, H; McDaniel, M; Pasare, C. Vps33B is a crucial regulator of Type I Interferon response downstream of the cGAS-STING pathway. Journal of immunology (Baltimore, Md. : 1950). 2020; 204:68.13.

Gao, Y; Deason, K; Jain, A; Irizarry-Caro, RA; Dozmorov, I; Coughlin, LA; Rauch, I; Evers, BM; Koh, AY; Wakeland, EK; et al. Transcriptional profiling identifies caspase-1 as a T cell-intrinsic regulator of Th17 differentiation. The Journal of Experimental Medicine. 2020; 217:e20190476.

Antoniou, K; Ender, F; Vollbrandt, T; Laumonnier, Y; Rathmann, F; Pasare, C; Singh, H; Koehl, J. Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40. Cells. 2020; 9:E300.

Jain, A; Irizarry-Caro, RA; McDaniel, MM; Chawla, AS; Carroll, KR; Overcast, GR; Philip, NH; Oberst, A; Chervonsky, AV; Katz, JD; et al. T cells instruct myeloid cells to produce inflammasome-independent IL-1β and cause autoimmunity. Nature Immunology. 2020; 21:65-74.

Khan, A; Bakhru, P; Saikolappan, S; Das, K; Soudani, E; Singh, CR; Estrella, JL; Zhang, D; Pasare, C; Ma, Y; et al. An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice. npj Vaccines. 2019; 4:34.

Grants

Innate mechanisms of regulation of Th17 responses
Principal Investigator.
National Institutes of Health (NIH) / National Institute of Allergy and Infectious Diseases (NIAID) 

Dates: Dec 2016 - Nov 2021

Role of BCAP in regulating inflammation and adaptive immunity
Principal Investigator.
National Institutes of Health / National Institute of Allergy and Infectious Diseases

Dates: Aug 2015 - Jan 2020

Endocytic Trafficking and Cell Signaling in Models of ARC Syndrome
Co-Investigator.
National Institutes of Health / National Institute of General Medical Sciences.

Dates: Apr 2017 - Mar 2021

Science Blog

Can Science Take the STING Out of Runaway Inflammation?
Autoimmune Disorders

Can Science Take the STING Out of Runaway Inflammation?

Chandrashekhar Pasare, DVM, PhD10/3/2023

New Leader for Immunobiology: Chandrashekhar Pasare, DVM, PhD
Infectious Diseases and Vaccines

New Leader for Immunobiology: Chandrashekhar Pasare, DVM, PhD

Chandrashekhar Pasare, DVM, PhD9/7/2023

Study to Decode Microbe-Gut Signaling Suggests Potential New Treatment For IBD
Digestive System

Study to Decode Microbe-Gut Signaling Suggests Potential New Treatment For IBD

Chandrashekhar Pasare, DVM, PhD4/3/2023

Contact Us

Chandrashekhar Pasare, DVM, PhD.

Chandrashekhar Pasare, DVM, PhD
Professor of Pediatrics, Division of Immunobiology

Phone: 513-803-3345
E-mail: Chandrashekhar.Pasare@cchmc.org

Give Today

3333 Burnet Avenue, Cincinnati, Ohio 45229-3026

© 1999-2024 Cincinnati Children's Hospital Medical Center. All rights reserved.

U.S. News & World Report Honor Roll Badge for Top Children's Hospital.Best Places to Work.America's Best Large Employers