Assistant Professor, Mellon Scholar, Richard King Mellon Institute for Pediatric Research, Department of Pediatrics
Assistant Professor, Department of Immunology
Member, Graduate Program in Microbiology and Immunology (PMI)
We now understand that humans exist as a combination of host cells and a vast consortium of bacteria, viruses and fungi, called the microbiota, that overwhelm the host both in terms of cell number and genetic information. The adaptive immune system has evolved alongside the microbiota and the cardinal feature of adaptive immunity, immune memory, may be an effort to ‘remember’ previous responses and shape subsequent host – microbial interactions. Such memory responses and protections can even be extended into children via the provision of antibodies in utero and maternal milk. Maintaining ‘friendly’ relations with the microbiota is a particular problem for the immune system because of the huge number of bacteria present that can be inflammatory depending upon the context within which they are experienced.
We are particularly interested in how the immune system deals with newly colonizing bacteria, as colonization events are dangerous for the host, since too little immune response can lead to infection but too much can contribute to autoinflammation. Our group hopes to identify the factors derived from host genetics, the environment (diet, infection etc.) and the microbiota that shape host colonization. Our hope is that this work will help us understand the root causes of diseases that are characterized by a disrupted relationship between the immune system and the microbiota, such as Necrotizing Enterocolitis, Crohn’s Disease, Colorectal cancer and Environmental Enteric Dysfunction.
Host-microbiome interaction during neonatal bacterial colonization
Characterization of memory T cell populations from the GI tract
Regulation of microbiota-specific effector/memory T cells
Role of diet in intestinal immunity and health
Role of microbiota-specific T cells in the development of colon cancer
Gopalakrishna K.P., Macadangdang B.R., Rogers M.B., Tometich J.T., Firek B.A., Baker R., Ji J., Burr A.H.P., Ma C., Good M., Morowitz M.J. and T.W. Hand. (2019) Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants. Nature Medicine. 25(7):1110-1115. PMID:31209335
Chiaranunt P., Tometich, J.T., Ji J. and T. W. Hand. (2018) T cell proliferation and colitis is initiated by defined intestinal microbes. Journal of Immunology. Jul 1;201(1):243-250. PMCID: PMC6082663.
Hand T.W.*, Vujkovic-Cvijin I., Ridaura V.K., Belkaid Y. Linking the microbota, chronic disease and the immune system. Trends Endocrinol Metab. 2016 Sep 9. S1043-2760(16)30106-0. PMID: 27623245 *Corresponding author
Hand T.W. The role of the microbiota in shaping infectious immunity. Trends Immunol. 2016 Oct;37(10):647-658. PMID: 27616558
Fonseca D.M.*, Hand T.W.*, Han S-J., Byrd, A.L., Gerner M.Y., Glatman Zaretsky A., Harrison O.J., Ortiz A.M., Quinones M., Trinchieri G., Brenchley J.M., Brodsky I.E., Germain R.N., Randolph G.J. and Y. Belkaid. Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity. Cell. 2015 In press. *These authors contributed equally to this work.
Belkaid Y. and T.W. Hand. Role of the microbiota in immunity and inflammation. Cell. 2014 Mar 27;157(1):121-41. PMID: 24679531
Hand T.W., Dos Santos L.M., Bouladoux N., Pagan A., Pepper M., Maynard C.L., Elson C.O. and Y. Belkaid. Acute Gastrointestinal Infection Induces Long-Lived Microbiota-Specific T cell Responses. Science. 2012 Sep 21;337(6101):1553-6. PMID: 22923434