Shekhar Pasare , PhD
Professor-Affiliate
Childrens Hospital Bldg R
COM Pediatrics Immunobiology - 0054
Research and Practice Interests
In my research, I pursue topics such as regulation of inflammation, dendritic cell biology, innate immunity, toll-like receptor signaling and the cross-talk between the innate and adaptive immune systems. Our lab’s primary goals are to understand how the innate and adaptive immune system interact with each other and to define the molecules that are part of this interaction.
We are also studying how inflammation is prompted by microbial recognition and during autoimmunity. In general, our objectives are 1) to obtain a molecular understanding of inflammation to develop new treatments for reducing autoimmunity and inflammation and 2) to define the complex communication between innate and adaptive immune systems in order to improve the design of vaccines.
Some of the most notable discoveries my colleagues and I have made include:
- Discovering a completely new pathway for inflammation in which auto-reactive T cells guide the innate immune system to produce IL-1beta; the new pathway may be used to treat auto-immunity
- Finding a new Toll-Like Receptor signaling adapter known as BCAP that reduces inflammation
Pathogen recognition via the innate immune system causes inflammation as well as adaptive immunity activation. One of my lab's major objectives is to identify the elaborate interaction and signaling between the innate and adaptive immune systems. My colleagues and I are specifically pursuing how the innate immune system prompts inflammation and how it affects both protective immunity and inflammatory conditions.
My research interests began due to my fascination with learning how the body’s immune system knows not to react to self but recognizes and responds to the microbial non-self. Our research has defined multiple new proteins and pathways in cells within innate and adaptive immune systems. We have utilized them as handles to direct questions regarding protective immunity, cancer and inflammatory diseases. We employ cutting-edge in vitro and in vivo methods in our research that may bring new targets to treat auto-immunity, cancer and inflammatory conditions.
Publications
Peer Reviewed Publications
McDaniel, Margaret M; Chawla, Amanpreet Singh; Jain, Aakanksha; Meibers, Hannah E; Saha, Irene; Gao, Yajing; Jain, Viral; Roskin, Krishna; Way, Sing Sing; Pasare, Chandrashekhar (2022. ) Effector memory CD4+ T cells induce damaging innate inflammation and autoimmune pathology by engaging CD40 and TNFR on myeloid cells.Science immunology, , 7 (67 ) ,eabk0182 More Information
McDaniel, Margaret M; Meibers, Hannah E; Pasare, Chandrashekhar (2021. ) Innate control of adaptive immunity and adaptive instruction of innate immunity: bi-directional flow of information.Current opinion in immunology, , 73 ,25-33 More Information
Brusilovsky, Michael; Rochman, Mark; Rochman, Yrina; Caldwell, Julie M; Mack, Lydia E; Felton, Jennifer M; Habel, Jeff E; Porollo, Aleksey; Pasare, Chandrashekhar; Rothenberg, Marc E (2021. ) Environmental allergens trigger type 2 inflammation through ripoptosome activation.Nature immunology, , 22 (10 ) ,1316-1326 More Information
Song, Ran; Gao, Yajing; Dozmorov, Igor; Malladi, Venkat; Saha, Irene; McDaniel, Margaret M; Parameswaran, Sreeja; Liang, Chaoying; Arana, Carlos; Zhang, Bo; Wakeland, Benjamin; Zhou, Jinchun; Weirauch, Matthew T; Kottyan, Leah C; Wakeland, Edward K; Pasare, Chandrashekhar (2021. ) IRF1 governs the differential interferon-stimulated gene responses in human monocytes and macrophages by regulating chromatin accessibility.Cell reports, , 34 (12 ) ,108891 More Information
Irizarry-Caro, Ricardo A; McDaniel, Margaret M; Overcast, Garrett R; Jain, Viral G; Troutman, Ty Dale; Pasare, Chandrashekhar (2020. ) TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation.Proceedings of the National Academy of Sciences of the United States of America, , 117 (48 ) ,30628-30638 More Information
Zhang, Jian; Tracy, Charles; Pasare, Chandrashekhar; Zeng, Jinsheng; Krämer, Helmut (2020. ) Hypersensitivity of Vps33B mutant flies to non-pathogenic infections is dictated by aberrant activation of p38b MAP kinase.Traffic (Copenhagen, Denmark), , 21 (9 ) ,578-589 More Information
Jain, Viral G; Kong, Fansheng; Kallapur, Suhas G; Presicce, Pietro; Senthamaraikannnan, Paranthaman; Cappelletti, Monica; Chougnet, Claire A; Bhattacharyya, Sandip; Pasare, Chandrashekhar; Muglia, Louis J (2020. ) IRAK1 Is a Critical Mediator of Inflammation-Induced Preterm Birth.Journal of immunology (Baltimore, Md. : 1950), , 204 (10 ) ,2651-2660 More Information
McDaniel, Margaret M; Kottyan, Leah C; Singh, Harinder; Pasare, Chandrashekhar (2020. ) Suppression of Inflammasome Activation by IRF8 and IRF4 in cDCs Is Critical for T Cell Priming.Cell reports, , 31 (5 ) ,107604 More Information
Gao, Yajing; Deason, Krystin; Jain, Aakanksha; Irizarry-Caro, Ricardo A; Dozmorov, Igor; Coughlin, Laura A; Rauch, Isabella; Evers, Bret M; Koh, Andrew Y; Wakeland, Edward K; Pasare, Chandrashekhar (2020. ) Transcriptional profiling identifies caspase-1 as a T cell-intrinsic regulator of Th17 differentiation.The Journal of experimental medicine, , 217 (4 ) , More Information
Antoniou, Konstantina; Ender, Fanny; Vollbrandt, Tillman; Laumonnier, Yves; Rathmann, Franziska; Pasare, Chandrashekhar; Singh, Harinder; Köhl, Jörg (2020. ) Allergen-Induced C5a/C5aR1 Axis Activation in Pulmonary CD11b+ cDCs Promotes Pulmonary Tolerance through Downregulation of CD40.Cells, , 9 (2 ) , More Information
Jain, Aakanksha; Irizarry-Caro, Ricardo A; McDaniel, Margaret M; Chawla, Amanpreet Singh; Carroll, Kaitlin R; Overcast, Garrett R; Philip, Naomi H; Oberst, Andrew; Chervonsky, Alexander V; Katz, Jonathan D; Pasare, Chandrashekhar (2020. ) T cells instruct myeloid cells to produce inflammasome-independent IL-1? and cause autoimmunity.Nature immunology, , 21 (1 ) ,65-74 More Information
Khan, Arshad; Bakhru, Pearl; Saikolappan, Sankaralingam; Das, Kishore; Soudani, Emily; Singh, Christopher R; Estrella, Jaymie L; Zhang, Dekai; Pasare, Chandrashekhar; Ma, Yue; Sun, Jianjun; Wang, Jin; Hunter, Robert L; Tony Eissa, N; Dhandayuthapani, Subramanian; Jagannath, Chinnaswamy (2019. ) An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice.NPJ vaccines, , 4 ,34 More Information
Jain, Aakanksha; Song, Ran; Wakeland, Edward K; Pasare, Chandrashekhar (2018. ) T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells.Nature communications, , 9 (1 ) ,3185 More Information
Kong, Fansheng; Liu, Zhiwei; Jain, Viral G; Shima, Kenjiro; Suzuki, Takuji; Muglia, Louis J; Starczynowski, Daniel T; Pasare, Chandrashekhar; Bhattacharyya, Sandip (2017. ) Inhibition of IRAK1 Ubiquitination Determines Glucocorticoid Sensitivity for TLR9-Induced Inflammation in Macrophages.Journal of immunology (Baltimore, Md. : 1950), , 199 (10 ) ,3654-3667 More Information
Raj, Prithvi; Rai, Ekta; Song, Ran; Khan, Shaheen; Wakeland, Benjamin E; Viswanathan, Kasthuribai; Arana, Carlos; Liang, Chaoying; Zhang, Bo; Dozmorov, Igor; Carr-Johnson, Ferdicia; Mitrovic, Mitja; Wiley, Graham B; Kelly, Jennifer A; Lauwerys, Bernard R; Olsen, Nancy J; Cotsapas, Chris; Garcia, Christine K; Wise, Carol A; Harley, John B; Nath, Swapan K; James, Judith A; Jacob, Chaim O; Tsao, Betty P; Pasare, Chandrashekhar; Karp, David R; Li, Quan Zhen; Gaffney, Patrick M; Wakeland, Edward K (2016. ) Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity.eLife, , 5 , More Information