Kenneth H. Cadwell

Assistant Professor; Skirball Institute of Biomolecular Medicine, Molecular Phathogenesis. Department of Microbiology

Ph.D., 2006 University of California, Berkeley

Keywords: Autophagy, Norovirus, Commensal Bacteria, Inflammatory Bowel Disease

 

 

Contact Information: 

Skirball Institute of Biomolecular Medicine
540 First Avenue 2nd floor, Lab 10
New York, N.Y. 10016
Office Tel: (212) 263-8891
Lab Tel: (212) 263-7491
Fax: (212) 263-5711
E-mail: ken.cadwell@med.nyu.edu

Administrative Contact:

Rachel Frank
Tel: (212)263-6281
Email: rachel.frank@med.nyu.edu

 


Host-Pathogen Interactions in Inflammatory Disease

Our laboratory is interested in how host-pathogen and host-commensal interactions determine the course of inflammation. Auto-inflammatory and autoimmune disorders such as diabetes and inflammatory bowel disease affect approximately 1 in 20 individuals, and many of these have limited treatment options due to insufficient understanding of disease mechanism. One pathway that has received much attention is autophagy, a process by which cellular material such as organelles and protein aggregates are captured in double-membrane vesicles and targeted to the lysosome for degradation. Several genes related to this pathway including Atg16L1 have been associated with Crohn’s disease, a major type of inflammatory bowel disease. Our ongoing experiments build on our novel observation that Atg16L1 mutant mice develop intestinal pathologies upon infection with a mouse norovirus (MNV). Much like the human disease, the intestinal inflammation that results from this virus-gene interaction is the result of an abnormal immune response to commensal bacteria.

The above experimental system provides a unique opportunity to investigate the origin and mechanism of complex inflammatory disorders. Current projects are utilizing cutting-edge approaches such as deep sequencing and germfree mice to address the following fundamental questions: How specific is this gene-virus interaction, and what makes MNV special? Does autophagy deficiency lead to inflammatory complications beyond the gastrointestinal tract? What is the relationship between MNV and commensal bacteria? By answering these questions, we hope to improve our basic understanding of mucosal immunity and how infectious agents are tolerated.

Selected Publications:

Wang, C., Mendonsa, G.R., Symington, J.W., Zhang, Q., Cadwell, K., Virgin, H.W. and Mysorekar, I.U. Proceedings of the National Academy of Sciences. 2012. Jul 3; 109(27):11008-13. PMID: 22715292

Hubbard, V.M. and Cadwell, K. Viruses, autophagy genes, and Crohn’s disease. Viruses. 2011. Jul; 3(7):1281-311. PMID: 21994779

Cadwell, K., Patel, K.K., Maloney, N., Liu, T.C., Ng, A.C.Y., Storer, C.E., Head, R.D., Xavier, R., Stappenbeck, T.S. and Virgin, H.W. Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell. 2010. Jun 25; 141(7): 1135-45. PMID: 20602997

Zhao, Z., Fux, B., Strong, D., Miller, B.C., Cadwell, K., Delgado, M., Pnopuak, M., Green, K.G., Schmidt, R.E., Mizushima, N.N., Deretic, V., Sibley, L.D. and Virgin, H.W. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host and Microbe. 2008. Nov 13;4(5):458-69. PMID: 18996346

Cadwell, K., Liu, J., Brown, S.L., Miyoshi, H., Loh, J., Lennerz, J., Kishi, C., KC, W., Carrero, J.A., Hunt, S., Stone, C., Brunt, E.M., Xavier, R.J., Sleckman, B.P., Li, E., Mizushima, N., Stappenbeck, T.S. and Virgin, H.W. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008. Nov 13;456(7219):259-63. PMID: 18849966

Click here to see all publications in PubMed