Timothy Hand, Ph.D.

Timothy Hand, Ph.D.

Contact

Campus: 4401 Penn Ave

Office: Rangos Building 8126

Pittsburgh, PA 15224

Ph: 412-692-9908

timothy.hand@chp.edu

Education

  • PhD, Yale University, 2009
  • Hon.B.Sc., University of Toronto, 2002

Academic Affiliation

  • Assistant Professor, Department of Pediatrics
  • Assistant Professor, Department of Immunology

About Research

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. 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.

 

Gastrointestinal infection is a particularly dangerous situation because it has the potential to put inflammatory obligate pathogens in the same space with benign members of the microbiota. Our group hopes to identify the factors derived from host genetics, the environment (diet, infection etc.) and the microbiota that shape the activation, differentiation, regulation and survival of T cells in the GI tract. Because adaptive immunity evolved within the context of the microbiota we believe that these mechanisms will be broadly applicable to our understanding of the immune system. 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 Crohn’s Disease and Environmental Enteropathy. 

 

Current Projects:

  1. Characterization of memory T cell populations from the GI tract
  2. Regulation of microbiota-specific effector/memory T cells
  3. Role of environmental context (diet, infection etc.) in the development of T cell responses against the microbiota
  4. Role of microbiota-specific T cells in the development of colon cancer
  5. Investigation of the factors that determine immunogenicity in a common commensal organism

Selected Publications

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.

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

Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014 Mar 27;157(1):121-41. PMID: 24679531

Belkaid Y.*, Bouladoux N. and T.W. Hand*. Effector and Memory T cell Responses to Commensal Bacteria. Trends in Immunol. 2013 Jun;34(6):299-306. PMID: 23643444*Co-corresponding authors