My research focuses on identifying the specific cells/molecules and underlying mechanisms that balance immunity and inflammation in the gut. Uncontrolled inflammation, as seen in inflammatory bowel disease (IBD), can be debilitating and can lead to life-threatening complications. Crohn’s disease and ulcerative colitis are both major forms of IBD which currently affects over 1.5 million Americans. Inflammation is a response to control infection; however, when uncontrolled the inflammatory response can harm the gastrointestinal tract. In IBD, chronic inflammation is driven by an abnormal immune response to the gut microbiota. This response is influenced by both genetic and environmental factors.
I am focused on understanding the role of macrophages and lymphocytes contributing to intestinal homeostasis and inflammation. Intestinal macrophages are the guardians of gut homeostasis. Intestinal macrophages interact with multiple cells in the intestine including epithelial cells, T cells, and innate lymphoid cells. Intestinal macrophages are chronically exposed to microbial signals and this is known to drive inhibitory signaling pathways that can dampen TLR and NOD signaling. Numerous genes associated with macrophage function have been linked to IBD. Currently, I am examining how these dysfunctional genes in macrophages can contribute to intestinal inflammation by shaping both the immune microenvironment and the gut microbiota.
Dr. Castillo earned his B.S. in Biology and M.S. in Chemistry from Eastern New Mexico University and his Ph.D. in Immunology from the University of Texas M.D. Anderson Cancer Center in Houston, TX.
S.W. Stonier, L.J. Ma, E.F. Castillo and K.S. Schluns (2008) Dendritic cells drive memory CD8 T cell homeostasis via IL-15 trans-presentation. Blood, 112(12): 4546-4554.
E.F. Castillo, S.W. Stonier, L. Frasca and K.S. Schluns (2009) Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation. J. Immunol., 183(8): 4948-4956.
E.F. Castillo, L.F. Acero, S.W. Stonier, D. Zhou and K.S. Schluns (2010) Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation. Blood, 116: 2494-2503.
W. Ma, B. Ortiz-Quintero, R. Rangel, M.R. McKeller, S. Herrera-Rodriguez, E.F. Castillo, K.S. Schluns, M. Hall, H. Zhang, W.K. Suh, H. Okada, T.W. Mak, Y. Zhou, M.R. Blackburn and H. Martinez-Valdez (2011) Coordinate activation of inflammatory gene networks, alveolar destruction and neonatal death in AKNA deficient mice. Cell Research, 21(11): 1564-1577.
E.F. Castillo, A. Dekonenko, J. Arko-Mensah, M. Mandell, N. Dupont, S. Jiang, M. Delgado-Vargas, G.S. Timmins, D. Bhattacharya, H. Yang, J. Hutt, C.R. Lyons, K.M. Dobos, and V. Deretic (2012) Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. PNAS, 109(46): E3168-E3176.
M.A. Firth, S. Madera, A.M. Beaulieu, G. Gasteiger, E.F. Castillo, K.S. Schluns, M. Kubo, P.B. Rothman, E. Vivier, and J.C. Sun. (2013) Nfil3-independent lineage maintenance and antiviral response of natural killer cells. J Exp Med. 210(13): 2981-2990.
N. Dupont, S. Chauhan, J. Arko-Mensah, E.F. Castillo, A. Masedunskas, R. Weigerth, T. Proikas-Cezanne, and V. Deretic. (2014) Neutral lipid stores and lipase PNPLA5 contribute to autophagosome biogenesis. Curr Biol., 24(6): 609-620.
K.T. Morris, E.F. Castillo, A.L. Ray, L. Weston, R. Nofchissey, J. Hanson, V. Samedi, and E.J. Beswick. (2015) Anti-G-CSF treatment induces protective tumor immunity in mouse colon cancer by promoting NK, macrophage and T cell responses. Oncotarget. 6(26):22338-22347.
A.L. Ray*, E.F. Castillo*, R.A. Nofchissey, L.L. Weston, V.G. Samedi, J.A. Hanson, I.V. Pinchuk, K.T. Morris and E.J. Beswick. (2015) Blockade of MK2 is protective in inflammation-associated colorectal cancer development. Int J Cancer. Aug 3. doi: 10.1002/ijc.29716. [Epub ahead of print] *Co-first authors
Review Articles
E.F. Castillo and K.S. Schluns (2012) Regulating the Immune System via IL-15 Transpresentation. Cytokine, 59: 479-490.
S. Jiang, N. Dupont, E.F. Castillo and V. Deretic (2013) Secretory vs. degradative autophagy: unconventional secretion of inflammatory mediators. J Innate Immunity, epub ahead of print.
S.B. Bradfute, E.F. Castillo, J. Arko-Mensah, S. Chauhan, S. Jiang, M. Mandell, and V. Deretic. (2013) Autophagy as an immune effector against tuberculosis. Curr Opin in Microbiol, 16(3): 355-365.
E. F. Castillo, A.L. Ray and E. J. Beswick (2016) MK2: An unrecogonized regulator of tumor promoting macrophages in colorectal cancer? Macrophage, 3: e1166.
