The Hand Lab for Immunity to Bacterial Colonization

When the Body Greets the Microbiome, it Doesn't Get a Second Chance to Make a First Impression

Humans are born sterile and soon after colonized by a vast consortium of microorganisms that we collectively call the microbiota. Our immune system must learn how to properly contain these mostly benign colonizers while remaining vigilant against invasion by more aggressive organisms.

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.

Areas of Focus

Deciphering how Intestinal Resident T cells are Shaped by the Local Microbiota

Hand Lab Focus IllustrationT cells at mucosal surfaces are critical to protection against invasive bacteria, viruses and parasites. However, if intestinal T cells become dysregulated, they can contribute to autoinflammatory diseases such as inflammatory bowel disease. We study how T cells in the small intestine and colon are shaped by the microbiome, both to the benefit and detriment of the host. We are interested in how interaction with specific micro-organisms can shape T cells to assist in vaccination and tumor immunotherapy. Alternatively, we are interested in how intestinal bacteria can shift T cells into inflammatory states, contributing to disease.


Delineating the Role of Maternal Antibodies in Shaping the Infant Microbiome

Hand Lab Oral Vaccination Cellular VisualThe immune system has a key role in the shaping of the microbiota. Maintaining homeostasis with regard to the microbiota is a lifelong process and shaped by the development of immunological memory against the bacteria that make up the microbiota. Infants are quickly colonized with bacteria that they have had no previous experience with and are therefore susceptible to both ineffective (leading to infection) and exaggerated (leading to damaging inflammation) immune responses against the microbiota. We hypothesize that one of the functions of maternal milk is to shape the developing microbiome towards health and that the primary mediators of that effort are antibodies, particularly Immunoglobulin A, secreted into the breast milk. This work has implications for many pediatric diseases and perhaps most notably necrotizing enterocolitis, where we have shown that disease is associated with a failure of IgA to bind to the bacteria present in the preterm intestine.


Understanding the Role of Diet in Shaping Mucosal Immune Responses

Hand Lab Immune Cellular Visual

The primary function of the intestine is the uptake of nutrients from the diet. As such, it is obvious that the diet can significantly modify the relationship between the host and the microbiota. However, this relationship is very complex because diet can affect both the microbiota and the immune response. We have developed a series of projects to begin to unravel this intricate relationship. We examine both malnourishment associated with food insecurity (nutrient restriction) but also over-abundance (High calories, processed sugar). Our goal is to understand how diet, via the microbiome contributes to diseases such as Inflammatory Bowel Disease and Environmental Enteric Dysfunction, a debilitating disease of children in resource poor nations.

Lab Team & Contact Information

Timothy W. Hand, PhD

Principal Investigator
timothy.hand@chp.edu
Read More>>

Amrita Bhattacharjee, PhD
Post-doctoral Fellow
amb427@pitt.edu

Hannah Bumgarner
Undergraduate Student Researcher
hab97@pitt.edu

Ansen Burr
MD/PhD Candidate
burr.ansen@medstudent.pitt.edu

Kathyayini Parlakoti Gopalakrishna, MBBS
PhD Candidate
kpg13@pitt.edu

Chelseá Johnson, MD
Post-doctoral Fellow, Neonatology
chelsea.johnson2@chp.edu

Abigail Overacre-Delgoffe
Post-doctoral Fellow
overacre@pitt.edu

Justin Tometich
Lab Manager/Technician
jut26@pitt.edu

Contact Us

The Hand Lab
UPMC Children’s Hospital of Pittsburgh
John G. Rangos Sr. Research Center, Suite 21
4401 Penn Avenue
Pittsburgh, PA 15224
412-692-9617

News & Activities

In the News

View current news featuring the research, staff and advancements of the Hand Lab at UPMC Children’s Hospital of Pittsburgh’s Richard King Mellon Institute for Pediatric Research. Please check back often for continued updates.

Another Reason Breast Is Best for Fragile Preemie Babies
U.S. News & World Report (6/17/19)

Mother's Milk Protects Premature Babies Against Deadly Infection - But Only if it Contains a Special Antibody, Study Finds
Daily Mail (6/17/2019)

Breastmilk’s IgA Protects Preemies From Deadly Disease
Genetic Engineering & Biotechnology News (6/18/2019)

HealthWatch: Breast Milk Helps Preterm Babies Fight Deadly Intestinal Disease
WJZ-13 CBS Baltimore (6/18/2019)

Natürlicher Schutz vor Gefürchtetem Darm-Notfall
Neue Zurcher Zeitung (6/22/2019)

Gli Anticorpi del Latte Materno che Proteggono i Bimbi Premature
Nostrofiglio (6/24/19)


Lab Activities and Achievements

2019

Abigail Overacre-Delgoffe, PhD, was honored with the Young Investigator Award from Society for Immunotherapy of Cancer.

Dr. Overacre-Delgoffe, was named Damon Runyon Cancer Research Foundation Post-doctoral Fellow.

Kathyayini Gopalakrishna, MBBS, and Dr. Overacre-Delgoffe won the Outstanding Poster and Oral Presentation at UPMC Children’s Hospital of Pittsburgh Research Day.

Dr. Gopalakrishna received a travel award from the Society for Mucosal Immunology to attend the International Congress of Mucosal Immunology in Brisbane, Australia.

Amrita Bhattacharjee, PhD, received the RAC Fellowship, UPMC Children’s Hospital of Pittsburgh.

Ansen Burr was named to the Autoimmunity and Immunopathology T32 Training Program.


Presentations at Scientific Meetings

2019

Timothy Hand, PhD, gave a Keynote presentation at the 8th Annual Meeting of the Graduate Program in Immunology, University of São Paulo, Brazil.

Dr. Gopalakrishna gave a Plenary Session presentation at the International Conference of Mucosal Immunology in Brisbane, Australia.

2018

Dr. Hand delivered the keynote address at the 2nd International Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Mexico City, Mexico.

Publications

Maternal IgA Protects Against the Development of Necrotizing Enterocolitis in Preterm Infants
Gopalakrishna KP, Macadangdang BR, Rogers MB, Tometich JT, Firek BA, Baker R, Ji J, Burr AHP, Ma C, Good M, Morowitz MJ, Hand TW
Nature Medicine
2019 Jun 17

Role of Nutrition, Infection, and the Microbiota in the Efficacy of Oral Vaccines
Bhattacharjee A, Hand TW
Clinical Science
2018 Jun 15

T Cell Proliferation and Colitis Are Initiated by Defined Intestinal Microbes
Chiaranunt P, Tometich JT, Ji J, Hand TW
The Journal of Immunology
2018 Jul 1

Linking the Microbiota, Chronic Disease, and the Immune System
Hand TW, Vujkovic-Cvijin I, Ridaura VK, Belkaid Y
Trends Endocrinology & Metabolism
2016 Dec

The Role of the Microbiota in Shaping Infectious Immunity
Hand TW
Trends in Immunology
2016 Oct

Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity 
Fonseca DM*, Hand TW*, Han SJ, Gerner MY, Glatman Zaretsky A, Byrd AL, Harrison OJ, Ortiz AM, Quinones M, Trinchieri G, Brenchley JM, Brodsky IE, Germain RN, Randolph GJ, Belkaid Y
Cell
2015 Oct 8

Role of the Microbiota in Immunity and Inflammation
Belkaid Y, Hand TW
Cell
2014 Mar 27

Acute Gastrointestinal Infection Induces Long-lived Microbiota-specific T cell Responses
Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagán AJ, Pepper M, Maynard CL, Elson CO 3rd, Belkaid Y
Science
2012 Sep 21

Opportunities to Join

We’d Like to Hear From You!

The Hand Lab is looking for talented post-doctoral fellows and graduate students interested in immune/microbiota interaction in the intestine. Please contact Dr. Hand via email if you are interested.