Cadwell Lab - Microbiology

Ken H. Cadwell, Ph.D.
Associate Professor, Department of Microbiology
Alexandria Center for Life Sciences – West Tower
430 East 29th Street
Office Rm. 409
Office: (212) 263-8891

Lab: (212) 263-7491
Email: ken.cadwell@med.nyu.edu
Lab Website

Administrative Assistant: Damien McDonald, (212) 263-6281
Email: Damien.Mcdonald@med.nyu.edu

 

KEY INTERESTS:

Crohn’s disease, inflammatory bowel disease, norovirus, virus, MNV, gastroenteritis, chronic infection, inflammation, mucosal immunity, host-pathogen, complex disease, intestine, autophagy, ATG16L1, commensal bacteria, NOD2
 

BIOGRAPHICAL DETAILS:

Graduate Education:

Ph.D. in Molecular Cell Biology in 2006, University of California, Berkeley

Postdoctoral Training:

2007-2011 Washington University School of Medicine

Academic Responsibilities:

2011-Present Assistant Professor of Microbiology,
Assistant Professor at Skirball Institute
Associate Editor, Autophagy
American Heart Association Micro Bsc2 Study Section

Honors:

Dale F. Frey Award for Breakthrough Scientist from the Damon Runyon Cancer Research Foundation
ICAAC Young Investigator Award

RESEARCH INTERESTS:

Our laboratory is interested in understanding what distinguishes infectious agents that cause disease (pathogens) from those that are innocuous. For example, the trillions of commensal bacteria in our gut are considered part of the microbiome, the collection of microorganisms that inhabit the body’s surfaces, and are thought to have many beneficial functions for the host. How does our immune system tolerate the presence of these bacteria? 

Using various mouse models of inflammatory disorders, we have been identifying host factors and microbial virulence strategies that determine the type of immune response generated against an infectious agent. In particular, we have made progress in understanding how the cellular pathway of autophagy and bacterial recognition by Nod2 contribute to Crohn’s disease, a major type of inflammatory bowel disease. 

In addition to bacterial members of the microbiome, we are interested in determining if the ‘virome’ has a similar role in physiology. The virome refers to the collection of viruses that inhabit the body, and although viruses are typically considered pathogens, it is becoming increasingly clear that they have complex long-term effects on the host. Consistent with this concept, we recently discovered that an intestinal virus in mice called murine norovirus (MNV) is able to provide benefits to the host in a manner similar to commensal bacteria. For example, MNV protects antibiotics-treated mice from intestinal damage. However, in a genetically susceptible host, MNV can also cause pathologies that are similar to those observed in Crohn’s disease patients.

Many serious disorders are due to unresolved inflammation triggered by infectious agents.  It is therefore critical that we define the factors and pathways that contribute to responses to pathogens and commensals, which may include viruses, bacteria, and other types of microbes.

 

PUBLICATIONS: 

Autophagy Mediates Tolerance to Staphylococcus aureus Alpha-Toxin.
Maurer K, Reyes-Robles T, Alonzo F 3rd, Durbin J, Torres VJ, Cadwell K.
Cell Host Microbe. 2015 Apr 8;17(4):429-40. doi: 10.1016/j.chom.2015.03.001. Epub 2015 Mar 26.
PMID: 25816775

Gastrointestinal Dissemination and Transmission of Staphylococcus aureus following Bacteremia.
Kernbauer E, Maurer K, Torres VJ, Shopsin B, Cadwell K.
Infect Immun. 2015 Jan;83(1):372-8.
PMID: 25385792

An enteric virus can replace the beneficial function of commensal bacteria.
Kernbauer E, Ding Y, Cadwell K.
Nature. 2014 Dec 4;516(7529):94-8.
PMID: 25409145

Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.
Hubbard-Lucey VM, Shono Y, Maurer K, West ML, Singer NV, Ziegler CG, Lezcano C, Motta AC, Schmid K, Levi SM, Murphy GF, Liu C, Winkler JD, Amaravadi RK, Rogler G, Dickinson AM, Holler E, van den Brink MR, Cadwell K.
Immunity. 2014 Oct 16;41(4):579-91.
PMID: 25308334

Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus.
Ramanan D, Tang MS, Bowcutt R, Loke P, Cadwell K
Immunity. 2014 Aug 21;41(2):311-24.
PMID: 25088769

Autophagy facilitates Salmonella replication in HeLa cells.
Yu HB, Croxen MA, Marchiando AM, Ferreira RB, Cadwell K, Foster LJ, Finlay BB.
MBio. 2014 Mar 11;5(2):e00865-14.
PMID: 24618251

Autophagy proteins control goblet cell function by potentiating reactive oxygen species production.
Patel KK, Miyoshi H, Beatty WL, Head RD, Malvin, NP, Cadwell K, Seglen PO, Dinauer MC, Virgin HW, Stappenbeck TS.
EMBO J. 2013 Dec 11;32(24):3130-44.
PMID: 24618251

A Deficiency in the Autophagy Gene Atg16L1 Enhances Resistance to Enteric Bacterial Infection.
Marchiando AM, Ramanan D, Ding Y, Gomez LE, Hubbard-Lucey VM, Maurer K, Wang C, Ziel JW, van Rooijen N, Nuñez G, Finlay BB, Mysorekar IU, Cadwell K.
Cell Host Microbe. 2013 Aug 14;14(2):216-24.
PMID: 23954160

FIP200 regulates the isolation membrane targeting of Atg16L1.
Nishimura T, Kaizuka T, Cadwell K, Himatbhai SM, Saitoh T, Akira S, Virgin HW, Mizushima N.  
EMBO Reports. 2013. Mar 1; 14(3):283-91.
PMID: 23392225

Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo.
Wang C, Mendonsa GR, Symington JW, Zhang Q, Cadwell K, Virgin HW, Mysorekar IU.
Proceedings of the National Academy of Sciences. 2012. Jul 3; 109(27):11008-13.
PMID: 22715292

Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine.
Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, Head RD, Xavier R, Stappenbeck TS, Virgin HW.
Cell. 2010 Jun 25;141(7):1135-45.
PMID: 20602997

A common role for Atg16L1, Atg5 and Atg7 in small intestinal Paneth cells and Crohn disease.
Cadwell K, Patel KK, Komatsu M, Virgin HW 4th, Stappenbeck TS.
Autophagy. 2009 Feb;5(2):250-2.
PMID: 19139628

Quantitation of selective autophagic protein aggregate degradation in vitro and in vivo using luciferase reporters.
Ju JS, Miller SE, Jackson E, Cadwell K, Piwnica-Worms D, Weihl CC.
Autophagy. 2009 May;5(4):511-9.
PMID: 19305149

Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes.
Stephenson LM, Miller BC, Ng A, Eisenberg J, Zhao Z, Cadwell K, Graham DB, Mizushima NN, Xavier R, Virgin HW, Swat W.
Autophagy. 2009 Jul;5(5):625-35.
PMID: 19276668

Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens.
Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D, Miller BC, Cadwell K, Delgado MA, Ponpuak M, Green KG, Schmidt RE, Mizushima N, Deretic V, Sibley LD, Virgin HW.
Cell Host Microbe. 2008 Nov 13;4(5):458-69.
PMID: 18996346

A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.
Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS, Virgin HW 4th.
Nature. 2008 Nov 13;456(7219):259-63.
PMID: 18849966

The autophagy gene ATG5 plays an essential role in B lymphocyte development.
Miller BC, Zhao Z, Stephenson LM, Cadwell K, Pua HH, Lee HK, Mizushima NN, Iwasaki A, He YW, Swat W, Virgin HW 4th.
Autophagy. 2008 Apr 1;4(3):309-14.
PMID: 18188005

An enteric virus can replace the beneficial function of commensal bacteria.
Kernbauer E, Ding Y, Cadwell K.
Nature. 2014 Dec 4;516(7529):94-8.
PMID: 25409145

Gastrointestinal Dissemination and Transmission of Staphylococcus aureus following Bacteremia.
Kernbauer E, Maurer K, Torres VJ, Shopsin B, Cadwell K.
Infect Immun. 2015 Jan;83(1):372-8.
PMID: 25385792

Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.
Hubbard-Lucey VM, Shono Y, Maurer K, West ML, Singer NV, Ziegler CG, Lezcano C, Motta AC, Schmid K, Levi SM, Murphy GF, Liu C, Winkler JD, Amaravadi RK, Rogler G, Dickinson AM, Holler E, van den Brink MR, Cadwell K.
Immunity. 2014 Oct 16;41(4):579-91. 
PMID: 25308334

Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus.
Ramanan D, Tang MS, Bowcutt R, Loke P, Cadwell K.
Immunity. 2014 Aug 21;41(2):311-24. 
PMID: 25088769

Autophagy facilitates Salmonella replication in HeLa cells.
Yu HB, Croxen MA, Marchiando AM, Ferreira RB, Cadwell K, Foster LJ, Finlay BB.
MBio. 2014 Mar 11;5(2):e00865-14. 
PMID: 24618251

PROFESSIONAL LINKS:
Skirball Institute


Immuno-fluorescence image of Paneth cells in the small intestine. Paneth cells generate antimicrobial granules (red) and are important for intestinal immunity. Both virus-infected ATG16L1 mutant mice and Crohn’s disease patients homozygous for ATG16L1 T300A have abnormal Paneth cells. Red = lysozyme, blue = nuclei.