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. The immune system also evolves in response to the microbiota in real-time and must learn to tolerate the microbiota from the first moments after birth so as to avoid damaging immunopathology. Maintaining ‘friendly’ relations with the microbiota is a particular problem for the immune system because of the huge number of bacteria present at barrier surfaces and the changing nature of the environment at these sites due to shifts in infection, diet or the behavior of the microbiota itself.
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 immune cells in the GI tract. Working at the Children’s Hospital, we have a particular focus on the early stages of the host-microbiota relationship during infancy and how they shape health long-term. 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 Enteric Disorder.
Professional Affiliations/Society Memberships
- American Association of Immunologists
- Society for Mucosal Immunology
- Faculty of 1000
- Grant Review, Wellcome Trust (U.K.)
- Grant Review, Deutsche Forschungsgemeinschaft (Germany)
Major Lectureships and Seminars
- “Establishing a New Gnotobiotic Facility: Education, Missions, and Accommodating Success,” Institute for Laboratory Animal Research workshop on Gnotobiotics, National Academy of Sciences, Washington, D.C., 2016
- “Long-term Immune Consequences of Gastrointestinal Infection,” Molecular Medicine Research Seminar, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA., 2016
- “A Holistic Approach to Immune-bacterial Interactions in the Gastrointestinal Tract,” Joint Immunology/ Microbiology Departmental Retreat, Pittsburgh, Pa., 2016
- “Chronic Effects of Acute Gastrointestinal Infection,” Senior Vice Chancellor Seminar Series, Pittsburgh, Pa., 2016
- “Staying Frenemies—the Love/Hate Relationship between the Microbiota and the Immune System,” Science 2016 Game Changers, Pittsburgh, Pa., 2016
- “Immunity to intestinal bacterial colonization,” Louisiana State University Veterinary College, Baton Rouge, La., 2017
- “Maternal Antibodies, the Neonatal Microbiota and Necrotizing Enterocolitis,” American Society for Investigative Pathology, Pittsburgh Pa., 2017
- “Maintenance of the Host/Microbiome Relationship in the Intestine,” Microbiology and Molecular Genetics Seminar, University of Pittsburgh, Pittsburgh Pa., 2017
- “Maintenance of the Host/Microbiome Relationship in the Intestine,” Molecular Medicine Research Seminar, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA., 2017
- “Maintenance of the Host/Microbiome Relationship in the Gastrointestinal Tract,” plenary speaker, CSH Meeting Fundamental Immunology & Its Therapeutic Potential, Cold Spring Harbor Laboratories, N.Y. 2017
Education & Training
- PhD: Yale University, New Haven, Conn.
- Bsc: University of Toroto
- 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.
- 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
- Hand T.W.. The Role of the Microbiota in Shaping Infectious Immunity. Trends Immunol. 2016 Oct;37(10):647-658. PMID: 27616558
- Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014 Mar 27;157(1):121-41. PMID: 24679531
The major goal of Timothy W. Hand’s research is to describe the role of immune response in intestinal disease. The laboratory is focused on the following projects.
The Role of Antibodies in Preventing the Development of Necrotizing Enterocolitis and Pediatric Crohn’s Disease. In collaboration with Mike Morowitz and Kevin Mollen, Hand is looking at whether monoclonal antibodies can be used to block the development of these diseases. In addition, he is investigating whether deficits in secreted antibody contribute to the development of disease.
Mucosal T-cell Memory. Hand is looking at the factors necessary for the development of an effective memory T-cell response in the gastrointestinal tract and how these may be affected by chronic gastrointestinal conditions.
T-cell Regulation and Inflammatory Bowel Disease. Hand is looking at the cellular requirements to prevent immunopathology in the gastrointestinal tract driven by T-cell responses against the commensal microbiota.
Immune Dysfunction in the Intestine of CF Patients. Using intestine-specific CF transmembrane conductance regulator knockout mice, the Hand lab is investigating whether loss of control over the microbiota by a dysfunctional immune response contributes to distal intestinal obstruction syndrome and cirrhosis.