Loke Lab - Microbiology
P'ng Loke, Ph.D.
Associate Professor, Department of Microbiology (Parasitology)
Alexandria Center for Life Sciences – West Tower
430 East 29th Street
Office Rm. 314
Office: (212) 263-8161
Fax: (212) 263-8116
Immunology, Parasitology, Microbiome, Inflammatory Bowel Disease, Chronic inflammation, Macrophage Activation, Type-2 Immunity, Atherosclerosis, Metabolic Diseases.
Graduate Education: 1996-2001 University of Edinburgh Ph.D
Postdoctoral Training: 2001-2004 University of California, Berkeley
2004-2007 University of California, San Francisco
Academic Appointments: 2007-2009 University of California, San Francisco
Assistant Research Immunologist
2009-2011 NYUMC, Assistant Professor
2014- NYUMC, Associate Professor
The Loke Lab studies the type-2 immune response against parasitic worms, or helminths. We want to understand the mechanisms that helminths and macrophages use to regulate our immune responses. Helminth infections are neglected diseases that cause enormous morbidity to populations predominantly in the developing world. However, they may also have properties that can prevent autoimmune diseases. Macrophages are ancient and important cells that regulate many aspects of mammalian physiology and are vital for host defense.
Helminths induce a population of macrophages that are dependent on type 2 cytokines (IL-4 and IL-13), also called alternatively activated M2 macrophages. M2 macrophages are critical for enabling the host to tolerate and resist helminth infections. We are characterizing the origin and functional properties of M2 macrophages during infection, as well as other inflammatory diseases, using a combination of intra-vital microscopy, cellular immunology and new strains of reporter mice.
We have also been studying how gastrointestinal helminths may regulate intestinal immune responses and interact with the gut microbiota. We characterized the response of an individual who self infected with helminths to treat his symptoms of ulcerative colitis in order to better understand how helminths could suppress inflammatory bowel diseases. We use mouse models, clinical trials and field studies in Malaysia to determine how helminths, the gut microbiota and intestinal immune responses interact.
1. Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
Girgis NM, Gundra UM, Ward LN, Cabrera M, Frevert U, Loke P.
PLoS Pathog. 2014 Jun 26;10(6):e1004080. doi: 10.1371/journal.ppat.1004080. eCollection 2014 Jun.
2. Helminth colonization is associated with increased diversity of the gut microbiota.
Lee SC, Tang MS, Lim YA, Choy SH, Kurtz ZD, Cox LM, Gundra UM, Cho I, Bonneau R, Blaser MJ, Chua KH, Loke P.
PLoS Negl Trop Dis. 2014 May 22;8(5):e2880. doi: 10.1371/journal.pntd.0002880. eCollection 2014 May.
3. Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct.
Gundra UM, Girgis NM, Ruckerl DA, Jenkins S, Ward LN, Kurtz ZD, Wiens KE, Basu-Roy U, Mansukhani A, Allen JE, Loke P.
Blood (In Press).
4. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences.
Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D, Zárate Rodriguez JG, Rogers AB, Robine N, Loke P, Blaser MJ.
Cell. 2014 Aug 14;158(4):705-21. doi: 10.1016/j.cell.2014.05.052.
5. 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. doi: 10.1016/j.immuni.2014.06.015. Epub 2014 Jul 31.
6. IL-22 producing CD4+ cells are depleted in actively inflamed colitis tissue.
Leung JM, Davenport M, Wolff MJ, Wiens KE, Abidi WM, Poles MA, Cho I, Ullman T, Mayer L, Loke P.
Mucosal Immunology 2013 May 22. doi: 10.1038/mi.2013.31.
7. Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
Broadhurst MJ, Ardeshir A, Kanwar B, Mirpuri J, Gundra UM, Leung JM, Wiens KE, Vujkovic-Cvijin I, Kim CC, Yarovinsky F, Lerche NW, McCune JM, Loke P.
PLoS Pathogens. 2012 Nov;8(11):e1003000.
8. Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice.
Broadhurst MJ, Leung JM, Lim KC, Girgis NM, Gundra UM, Fallon PG, Premenko-Lanier M, McKerrow JH, McCune JM, Loke P.
PLoS Pathog. 2012;8(8):e1002883. doi: 10.1371/journal.ppat.1002883. Epub 2012 Aug 23.
9. Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity.
Wei J, Loke P, Zang X, Allison JP. J
Exp Med. 2011 Aug 1;208(8):1683-94.
10. IL-22+ CD4+ T cells are associated with therapeutic Trichuris trichiura infection in an ulcerative colitis patient.
Broadhurst MJ, Leung JM, Kahsyap V, McCune JM, Mahadevan U, McKerrow JH, Loke P.
Science Translational Medicine 2010 Dec 1;2(60):60ra88.
PUBLISHED REVIEWS, BOOKS, AND BOOK CHAPTERS:
Systemic impact of intestinal helminth infections.
Mishra PK, Palma M, Bleich D, Loke P, Gause WC.
Mucosal Immunol. 2014 Apr 16.
Parasites: what are they good for?
Stumhofer JS, Loke P.
Curr Immunol Rev. 2013 Aug 1;9(3):120-128.
Immune Regulation during Helminth Infections.
Girgis NM, Gundra UM, Loke P.
PLoS Pathogens. 2013 Apr;9(4):e1003250. doi: 10.1371/journal.ppat.1003250. Epub 2013 Apr 18.
A role for IL-22 in the relationship between intestinal helminths, gut microbiota and mucosal immunity.
Leung JM, Loke P.
Int J Parasitol. 2012 Nov 20. doi:pii: S0020-7519(12)00295-0.
Helminthic therapy: improving mucosal barrier function.
Wolff MJ, Broadhurst MJ, Loke P.
Trends Parasitol. 2012 May;28(5):187-94.
Proteases in Parasitic Diseases.
McKerrow JH, Caffrey C, Kelly B, Loke P, Sajid M.
Annual Reviews of Pathology 2006 Feb: 1: 497-536.
Emerging mechanisms of immune-regulation: the extended B7 family and regulatory T cells.
Loke P and Allison JP.
Arthritis Research & Therapy. 2004;6(5):208-14.
Divergent roles for macrophages in lymphatic filariasis.
Allen JE and Loke P.
Parasite Immunology 2001 Jul;23(7):345-52.
Suppressive antigen-presenting cells in Helminth infection.
MacDonald AS, Loke P, Allen JE