Timothy W. Hand, PhD
- Director, Gnotobiotic Animal Core Laboratory and Assistant Professor of Pediatrics
- Scholar, Richard King Mellon Foundation Institute for Pediatric Research
Administrative Assistant: Lisa M. Summe, MFA, MA
The laboratory of Timothy Hand, PhD, is interested in the immune cells of the intestine and how they respond to the first interactions with colonizing microorganisms. How the immune system deals with newly colonizing bacteria is important, since too little immune response can lead to infection but too much can contribute to damaging inflammation. The intestine is home to the largest and densest group of microorganisms in the body and the intestinal microbiome is required for many host processes, most notably the digestion of complex carbohydrates. Therefore, maintaining a healthy relationship with the microbiome is important for the health of the host. Shifts in the intestinal microbiota and the mucosal immune response have been associated with a variety of important pediatric diseases including inflammatory bowel disease, diabetes, necrotizing enterocolitis and asthma.
Our view is that the long- term relationship between the host and the microbiome can be shaped by the results of their initial interaction by the phenomenon of immunological memory. Therefore, we seek to better understand the immune systems ‘first impressions’ of the microbiota and how they are shaped by environmental factors such as diet and inflammation. Our hope is that a better understanding of how the microbiome shapes the host will lead to better therapies for pediatric disease.
Professional and Scientific Society Memberships
- American Association of Immunology, 2006-Present
- Society for Mucosal Immunology, 2016-Present
- Faculty of 1000, 2017-2019
Education & Training
- BSc, Immunology, high distinction, Trinity College-University of Toronto, 2002
- PhD, Immunology, Yale University, 2009
- Postgraduate Work, Immunology, Yale University, 2009
- Postgraduate Work, Immunology, National Institutes of Health, 2009-2015
Castillo-dela Cruz P., Wanek A.G., Kumar P., An X., Elsegeiny W., Horne W., Fitch A., Burr A.H.P., Gopalakrishna K.P., Chen K., Methé B.A., Canna S.W., Hand T.W. and J.K. Kolls. Intestinal IL-17R signaling constrains IL-18 driven liver inflammation by the regulation of microbiome-derived products. Cell Reports. 2019 Nov 19;29(8):2270-2283. PMID: 31747600
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 2019 Jun 17. Jul;25(7):1110-1115 PMID: 31209335
Majumder S., Amatya N., Revu S., Jawale C.V., Wu D., Rittenhouse N., Menk A., Kupul S., Du F., Raphael I., Bhattacharjee A., Siebenlist U., Hand T.W., Delgoffe G.M., Poholek A.C., Gaffen S.L., Biswas P.S. and M.J. McGeachy IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival. Nature Immunology 2019 May;20(5):534-545. PMID: 30962593
Chiaranunt P., Tometich, J.T., Ji J. and T. W. Hand. T cell proliferation and colitis is initiated by defined intestinal microbes. J Immunol. 2018 Jul 1;201(1):243-250. PMID: 29777027
Edwards J.P., Hand T.W., Fonseca D.M., Glass D.D., Belkaid Y., Shevach E.M. The GARP/Latent TGF-β1 complex on Treg cells modulates the induction of peripherally derived Treg cells during oral tolerance. Eur J Immunol. 2016 Apr 8. doi: 10.1002/eji.201546204 PMID: 27062243.
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 Oct 8;163(2):354-66. PMID: 26451485 *These authors contributed equally to this work.
Askenase MH, Han SJ, Byrd AL, Morais da Fonseca D, Bouladoux N, Wilhelm C, Konkel JE, Hand TW, Lacerda-Queiroz N, Su XZ, Trinchieri G, Grainger JR, Belkaid Y. Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection. Immunity. 2015 Jun 16;42(6):1130-42. PMID: 26070484
Peters N.J., Pagan A.J., Lawyer P.J., Henrique Roma E., Stamper L.W., Hand T.W. and D.L. Sacks. Short-lived effector CD4+ T cells directly migrate to the dermal site of challenge and mediate protection in a parasitic model of concomitant immunity. PLoS Pathogens. 2014 Dec 4;10(12):e1004538. PMID: 25473946
Molloy M.J., Bouladoux N., Grainger J.R., Hand T.W., Quinones M., Dzutsev A.K., Goa J., Trinchieri G., Murphy P.M., and Y. Belkaid. Intra-luminal Containment of Commensal Outgrowth in the Gut during Infection-Induced Dysbiosis. Cell Host and Microbe. 2013 Sep 11;14(3):318-28. PMID: 24034617
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
NIH R21, Defining the role of the mucosal immune response and microbiota in enteropathy-driven oral vaccine failure, 2019-2021, $275.000.
NIH R01, Defining the mechanism of protection of maternal IgA against Necrotizing Enterocolitis, 2019-2024, $330,307.