Description of Research Expertise

Research Interests:
Host-microbe interactions in the gut and inflammatory disease

Keywords:
Gut microbes, autophagy, inflammatory bowel disease, virology, microbial pathogenesis, microbiota, helminths, mucosal immunity

Research Details:
My laboratory investigates how our immune system has adapted to the diverse microbial agents we encounter in our lifetime. We address this question by focusing on the gastrointestinal tract where a single layer epithelium separates our body from pathogens and microbial colonizers belonging to the microbiota. Through taking a comparative infection biology approach, our research has identified cellular mechanisms underlying the balanced immune response that is necessary for responding to life-threatening infections while avoiding chronic illnesses like inflammatory bowel disease. Ongoing projects include elucidating how symbiotic intestinal viruses, fungi, and parasites contribute to local and extraintestinal disease susceptibility, defining how the cellular pathway of autophagy mediates resilience towards infectious threats, and understanding how polymicrobial exposure in the natural environment contributes to the developmental maturation of the immune system. Through these projects, we hope to gain further insight into how microbial diversity in the intestinal ecosystem shapes host physiology and pave the way for therapies that restore balanced host-microbe relationships.

Lab Personnel:
Hairu Yang – senior scientist
Kasiani Terzoglou - technician
Kyungku Jang - postdoctoral fellow
Ying-Han Chen - postdoctoral fellow
Xiaomin Yao - postdoctoral fellow
Lucie Bernard - postdoctoral fellow
Christin Herrmann - postdoctoral fellow
Wataru Ebina - postdoctoral fellow
Christopher Cowley - postdoctoral fellow
Yi Yang - postdoctoral fellow
Gavyn Chern Wei Bee - postdoctoral fellow
Eugene Rudensky - student
Alannah Lejeune - student
Kimberly Zaldana - student
Chaoting Zhou - student

Selected Publications

Chen YH, Yeung F, Lacey KA, Zaldana K, Lin JD, Bee GCW, McCauley C, Barre RS, Liang SH, Hansen CB, Downie AE, Tio K, Weiser JN, Torres VJ, Bennett RJ, Loke P*, Graham AL*, and Cadwell K.: Rewilding of laboratory mice remedies reduced granulopoiesis and sustains enhanced immunity through intestinal fungal colonization. Science Immunology : 2023.

Matsuzawa-Ishimoto Y, Yao X, Koide A, Ueberheide BM, Axelrad JE, Reis BS, Parsa R, Neil JA, Devlin JC, Rudensky E, Dewan MZ, Cammer M, Blumberg RS, Ding Y, Ruggles KV, Mucida D, Koide S* and Cadwell K*.: Gamma delta IEL effector API5 masks genetic susceptibility to Paneth cell death. Nature 610 (7932): 547-554,2022.

Ching KL, de Vries M, Gago J, Dancel-Manning K, Sall J, Rice WJ, Barnett C, Liang FX, Thorpe LE, Shopsin B, Segal LN, Dittmann M*, Torres VJ*, Cadwell K*: ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection. PLoS Biol 20 (9): e3001754,2022.

Venzon M, Das R, Luciano DJ, Burnett J, Park HS, Devlin JC, Kool ET, Belasco JG, Hubbard EJA*, Cadwell K*: Microbial byproducts determine reproductive fitness of free-living and parasitic nematodes. Cell Host & Microbe 5 (22): S1931-3128,2022.

Dallari S, Heaney T, Rosas-Villegas A, Neil JA, SY, Brown JJ, Urbanek K, Herrmann C, Depledge DP, Dermody TS, Cadwell K.: Enteric viruses evoke broad host immune responses resembling bacterial microbiome Cell Host & Microbe. 29 (6): 1014-1029,2021.

Yeung F, Chen YH, Lin JD, Leung JM, McCauley C, Devlin JC, Hansen C, Cronkite A, Stephen J, Drake-Dunn C, Fulmer Y, Shopsin B, Ruggles KV, Round JL, Loke P*, Graham AL*, Cadwell K*.: Altered immunity of laboratory mice in the natural environment is associated with fungal colonization Cell Host & Microbe 27 (5): 809-822.e6,2020.

Keller MD, Ching KL, Liang FX, Dhabaria A, Tam K, Ueberheide BM, Unutmaz D, Torres VJ*, Cadwell K: Decoy exosomes provide protection against bacterial toxins Nature 579 (7798): 260-264,2020.

Martin PK, Marchiando A, Xu R, Rudensky E, Yeung F, Schuster SL, Kernbauer E, Cadwell K.: Autophagy proteins suppress protective type I interferon signaling in response to the gut microbiota. Nat Microbiol 3 (10): 1131-1141,2018.

Ramanan D, Bowcutt R, Lee SC, Tang MS, Kurtz ZD, Ding Y, Honda K, Gause WC, Blaser MJ, Bonneau RA, Lim YA, Loke P*, Cadwell K*.: Helminth Infection Promotes Colonization Resistance via Type 2 Immunity Science 352 (6285): 608-12,2016.

Kernbauer E, Ding Y, Cadwell K.: An enteric virus can replace the beneficial function of commensal bacteria Nature 516 (7529): 94-8,2014.

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Academic Contact Information

421 Curie Boulevard
Philadelphia, PA 19104
Phone: 215-573-1076