Major Areas of Research
- Role of the microbiota in immunity to infection
- Role of dietary metabolites in promoting immune regulation and immune responses to pathogens
- Tissue specific regulatory responses to infection
- Leishmania major, Toxoplasma gondii, Cryptosporidium and Microsporidium spp
Our laboratory aims to understand the mechanisms controlling host microbe interactions at barrier sites such as the skin and the gut. These two sites represent the first portal of pathogen exposure and are major anatomical sites for development of inflammatory disorders. The skin and the gut also represent highly specialized environments with distinct structures, cell types, and innate defense mechanisms tailored to support their individual challenges. These include their exposure to factors from the outside environment, to dietary antigens, and to antigens derived from resident commensals. In particular, all barrier surfaces are covered by a diverse and abundant microbiota that play a dominant role in host physiology and immunity. However, this symbiotic relationship also poses a constant threat to the host, and aberrant reactivity against commensals can lead to life-threatening tissue damage. These conflicting pressures present the host system that defends the skin or the gut with unique challenges: tolerating constant exposure to innocuous antigens while simultaneously maintaining the capacity to rapidly respond to encounters with pathogens.
Because of the inherent complexity of these challenges, understanding how the immune system functions at barrier sites needs to be addressed in an integrated and multidisciplinary manner. In this context, our work has demonstrated that 1) commensals play a major role in the control of host defense in both the skin and the gastrointestinal tract, 2) dietary factors control the induction of effector and regulatory responses in the gut, 3) the gut compartment is a major site of induction of T cells and dendritic cells with regulatory functions, and 4) acute infections can have permanent consequences on tissue immunity.
Using a range of dermal and gastrointestinal pathogens (Leishmania sp., Cryptosporidium sp., Microsporidium sp., Toxoplasma sp., and Yersinia pseudotuberculosis) our laboratory currently further explores
- Function of the microbiota in the control of tissue immunity and pathogen infection
- Mechanism by which the microbiota control tissue immunity and inflammation
- Unique strategies developed by each tissue to maintain its integrity during inflammation
Dr. Yasmine Belkaid obtained her Ph.D. in 1996 from the Pasteur Institute in France on innate responses to Leishmania infection. Following a postdoctoral fellowship at NIAID on immune regulation during Leishmania infection, she joined the Children’s Hospital Research Foundation in Cincinnati as an assistant professor in 2002. In 2005, she joined the Laboratory of Parasitic Diseases as a tenure-track investigator. Since 2008, she has worked as an adjunct professor at the University of Pennsylvania.
Nicolas Bouladoux, Ph.D.
Nicolas obtained his bachelor’s degree in cellular biology and his master’s degree in biochemistry and immunology from the Faculty of Science at Paris-Sud University in Orsay, France. He received his Ph.D. from Pierre and Marie Curie University in Paris, studying the intestinal immune responses against microsporidia, a group of opportunistic intracellular parasites causing gastrointestinal diseases in humans. His research focuses on understanding how different commensal species interact with the host immune system and how such interactions help protect the host from harmful pathogens.
Allyson Byrd, M.S.
Ph.D. Candidate, Boston University/NHGRI/NIAID
Allyson obtained her bachelor’s degree in genetics from the University of Georgia, Athens. She is currently working on her Ph.D. in bioinformatics from Boston University. In collaboration with Julie Segre in the National Human Genome Research Institute, Allyson is strain tracking bacteria in metegenomic samples of the skin microbiome. By analyzing the strains present in healthy individuals, she hopes to understand whether certain strains of bacteria play a role in the progression of skin diseases, such as atopic dermatitis.
Nicholas Collins, Ph.D.
Postdoctoral Visiting Fellow
Nick received his bachelor’s degree and Ph.D. at the University of Melbourne, focusing on the role of memory T cells in skin during viral infection. His current work will investigate the role of memory T cells in the context of secondary infections in different tissues throughout the body.
Michael G. Constantinides, Ph.D.
Cancer Research Institute Irvington Postdoctoral Fellow
Mike received his bachelor’s degree from Princeton University, with a major in chemistry and a minor in materials science. He completed his Ph.D. at the University of Chicago, where he studied the development of innate lymphoid cells and natural killer T cells in the laboratory of Dr. Albert Bendelac. His current research aims to determine how the microbiome affects lung immunity.
Vinicius de Andrade-Oliveira, Ph.D.
Pew Latin American Fellow
Vinicius received his Ph.D. in 2014 in immunology at the University of Sao Paulo, Brazil, working on the role of short chain fatty acids and kidney disease. During his period, he spent one year I Jonathan Powell’s lab at Johns Hopkins working on T cell metabolism. He followed at USP for post doc working on metabolism and skin transplantation. As a postdoctoral visiting fellow, his work intends to explore the development of chronic diseases after acute infections.
Arielle Glatman Zaretsky
IRTA Postdoctoral Fellow, Helen Hay Whitney Postdoctoral Fellow (April 2016)
Ari received her bachelor's degree in biology from Brown University. She obtained her Ph.D. from the University of Pennsylvania in 2014 for her studies evaluating the development and maintenance of humoral responses. Her research in the Mucosal Immunology Section focuses on the mechanisms of lymphatic function and repair after acute infection.
Seong-Ji Han, M.Sc., Ph.D
Postdoctoral Research Fellow
Seong-Ji Han obtained her bachelor’s degree and Master’s degree in biochemistry at the Free University of Berlin in Germany. She did her Ph.D research at the University of California, Berkeley, and received her Ph.D. from the Free University of Berlin studying the immune response toToxoplasma gondii. Her current research in the Mucosal Immunology Section focuses on understanding immunity in the adipose tissue.
Oliver J. Harrison, D.Phil.
Postdoctoral Visiting Fellow
Oliver obtained his Master's degree in pharmacology from the University of Bath (UK), and his Wellcome Trust-funded D.Phil. in infection, immunology, and translational medicine from the University of Oxford (UK), studying IL-1 family cytokines in intestinal health and disease, under the supervision of Dr. Kevin Maloy. At NIH, his research focuses on the regulation of commensal-specific T-cell responses during homeostasis and inflammation.
Jonathan L. Linehan, Ph.D.
Postdoctoral Research Associate (PRAT) Fellow
Jon obtained his bachelor’s degree in genetics, cell biology, and development from the University of Minnesota. He received his Ph.D. in the microbiology, immunology, and cancer biology program also at the University of Minnesota studying the generation and maintenance of Th17 cells in response to infection. His current research focuses on understanding the mechanisms underlying the induction of commensal microbe-specific T-cell responses in skin.
E. Dean Merrill, B.A.
Medical Research Scholars Program-Research Scholar
Dean graduated from the University of Pennsylvania in 2008 with a bachelor’s degree in economics and recently completed his third year of medical school at the University of Missouri-Kansas City School of Medicine. He is currently a research scholar in the 2015 – 2016 Medical Research Scholars Program. Upon completion of his work in Dr. Belkaid’s lab, Dean will apply for a residency in dermatology. Dean’s research interests include the role of the gastrointestinal and cutaneous microbiota in distant and site-specific immunity.
Saeko Nakajima, M.D., Ph.D.
JSPS Research Fellowships for Young Scientists Postdoctoral Fellow
Saeko obtained her M.D. from Osaka Medical College, Japan. She received her Ph.D. from Kyoto University studying the role of prostaglandin I2 in a murine model of contact hypersensitivity and the role of Langerhans cells in a murine model of atopic dermatitis. She also practiced clinical dermatology in Japan. Her current research focuses on the crosstalk between skin commensals and skin immune cells under infectious and inflammatory conditions.
Samira Tamoutounour, Ph.D.
IRTA Postdoctoral Fellow, EMBO Fellow
Samira obtained her bachelor’s degree at the University of Rouen in France. She later moved to the University of Aix-Marseille, France, where she achieved her Master’s degree and her Ph.D research at the Centre d'Immunologie Marseille Luminy on the origin and the function of dendritic cells and macrophages in the skin. Her research focuses on understanding skin immune cells’ behavior changes in response to skin microbiota.
Ivan Vujkovic-Cvijin, Ph.D.
IRTA Postdoctoral Fellow
Ivan received his B.S. in biochemistry-molecular biology from the University of California, Santa Barbara, and obtained his Ph.D. at the University of California, San Francisco, where he studied the influence of the gut microbiome on the human immune system during HIV disease. His current research in the Mucosal Immunology Section focuses on defining mechanisms of microbiome-mediated control of human 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. Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity. Cell. 2015 Oct 8;163(2):354-66.
Naik S, Bouladoux N, Linehan JL, Han SJ, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd AL, Deming C, Quinones M, Brenchley JM, Kong HH, Tussiwand R, Murphy KM, Merad M, Segre JA, Belkaid Y. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature. 2015 Apr 2;520(7545):104-8.
Spencer SP, Wilhelm C, Yang Q, Hall JA, Bouladoux N, Boyd A, Nutman TB, Urban JF Jr, Wang J, Ramalingam TR, Bhandoola A, Wynn TA, Belkaid Y. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science. 2014 Jan 24;343(6169):432-7.
Grainger JR, Wohlfert EA, Fuss IJ, Bouladoux N, Askenase MH, Legrand F, Koo LY, Brenchley JM, Fraser ID, Belkaid Y.Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat Med. 2013 Jun;19(6):713-21.
Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quimones M, Koo L, Conlan S, Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, Trinchieri G, Segre JA, Belkaid Y. Compartmentalized control of skin immunity by resident commensals. Science. 2012 Aug 31;337(6098):1115-9.
Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagan AJ, Pepper M, Maynard CL, Elson CO 3rd, Belkaid Y. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science. 2012 Sep 21;337(6101):1553-6.
Valenzuela JG, Belkaid Y, Kamhawi S, Sacks D, Ribeiro JMC, inventors; The Government of the United States of America as represented by the Secretary Department of Health and Human Services, assignee. Anti-arthropod vector vaccines, methods of selecting and uses thereof. United States patent US 7,964,576. 21 Jun 2011.
Valenzuela JG, Ribiero JMC, Kamhawi S, Belkaid Y, Fischer L, Audonnet JC, Milward F, inventors; The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services, Merial Limited, assignees. P. ariasi polypeptides, P. perniciosus polypeptides and methods of use. United States patent US 7,741,437. 22 Jun 2010.
Valenzuela JG, Belkaid Y, Kamhawi S, Sacks D, Ribeiro JMC, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Anti-arthropod vector vaccines method of selecting and uses thereof. United States patent US 7,388,089. 17 Jun 2008.