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
For more about Dr. Belkaid's research, see The Microbiome: When Good Bugs Go Bad.
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.
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.
Michel Enamorado, Ph.D.
Postdoctoral Visiting Fellow
Michel received his B.S. in Biochemistry from University of Havana. Then he moved to Madrid where he did his Ph.D. research in the Immunobiology Lab at CNIC, and received his Ph.D. in Molecular Biosciences/Immunology in 2017 from Autonomous University of Madrid. During his Ph.D., he was studying the interaction between circulating and tissue-resident memory CD8+ T cells in tumor immunity. In addition, he was focused in how mitochondrial metabolism regulates macrophages and dendritic cells functions. His current research focuses on understanding how immune-cell-metabolism impacts physiological processes such as barrier-tissue homeostasis, instruction for tolerance, and crosstalk with the microbiota.
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 Metaorganism Immunity Section focuses on understanding immunity in the adipose tissue.
Oliver J. Harrison, D.Phil.
Postdoctoral Visiting Fellow
Ollie obtained his D.Phil from the University of Oxford, focusing on the role of IL-1 family cytokines in intestinal inflammation. His current research in the Metaorganism Immunity Section focuses on the regulation of pathogen and commensal-specific T-cell responses during homeostasis and inflammation.
Charlotte Hurabielle, M.D.
Ph.D. student, Paris Diderot University
Charlotte obtained her master's degree in immunology from Paris Descartes University in Paris, France. She received her M.D. In Dermatology from Paris Descartes University in Paris, France. Her current work is to investigate how aberrant responses to skin microbes can contribute to the etiology of inflammatory diseases.
Djalma Lima Junior
Pew Latin Amerian Fellow
Djalma received his bachelor's degree in biology from Ouro Preto University/ Brazil. In 2013, he obtained his Ph.D. in Immunology at the Ribeirão Preto Medical School/ São Paulo University. During this time, his studies focused in the role of innate immune sensors after Leishmania infection. As a postdoctoral visiting fellow, his research in the Metaorganism Immunity Section focuses to investigate the interference of obesity in the skin microbiota metabolism and how this process can influence in the skin immune tone.
Siddharth Krishnamurthy, Ph.D.
IRTA Postdoctoral Fellow
Sidd received his BS/MS in Microbiology from the University of California, San Diego, and obtained his Ph.D. in Immunology at Washington University in Saint Louis, where he focused on creating novel computational methods to discover viruses and characterizing novel RNA phages. His current research in the Metaorganism Immunity Section focuses on understanding the role of the virome in immunity.
Pete Warakorn Kulalert, Ph.D.
Damon Runyon Cancer Research Foundation Postdoctoral Fellow
Pete received his bachelor's in 2010 from Harvard College and completed his PhD in 2017 from Massachusetts Institute of Technology. During his PhD, he studied neuroendocrine regulation of C. elegans development and stress physiology. His current research explores the neuroimmune interactions mediated by the skin microbiota.
Ai Ing Lim, Ph.D.
Visiting Postdoctoral Fellow
Ai Ing is originally from Malaysia. She received her Master degree from The University of Hong Kong. She then moved to Paris for her PhD funded by Marie Skłodowska-Curie actions in James Di Santo's lab at Institut Pasteur and discovered human ILC precursors are circulating in the peripheral blood of healthy individual. She is current trying to understand the microbial-driven maternal-fetal immune crosstalk.
Apollo Stacy, Ph.D.
IRTA Postdoctoral Fellow
Apollo obtained his bachelor's in 2010 from Washington University in St. Louis and completed his PhD in 2017 from The University of Texas at Austin. During his PhD, he studied interspecies bacterial interactions that enhance pathogen virulence. His current research examines how host lifestyle choices, such as diet, exercise, and daily routines, alter the host immune response and susceptibility to polymicrobial infections.
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 keratinocytes' biology in response to skin microbiota.
Ivan Vujkovic-Cvijin, Ph.D.
Cancer Research Institute Irvington 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 Metaorganism Immunity Section focuses on defining mechanisms of microbiome-mediated control of human immunity.
Taylor Farley, B.S.
D.Phil Student, University of Oxford
Taylor received her B.S. in Microbiology from Colorado State University. Following her degree, she was awarded an NIH post-baccalaureate fellowship where she studied the role of a TNF superfamily member, TL1A, in multiple models of autoimmune disease. Currently, she is focusing her research on non-classical immunity to the microbiome in patients with inflammatory disorders.
Verena Link, Ph.D.
Verena received her bachelor’s and master’s degree in bioinformatics from the Ludwig Maximilian University of Munich and the Technical University of Munich. During her Ph.D. at the Ludwig Maximilian University of Munich she did her research in the laboratory of Dr. Chris Glass at the University of California, San Diego studying the effect of natural genetic variation on the epigenetic and transcriptional profile of murine macrophages. Her current research focuses on understanding how the microbiome influences the transcriptome and epigenome of a diverse set of immune cells.
Hugh Welles, Ph.D.
IRTA Posdoctoral Fellow
Hugh received his Ph.D. from the George Washington University as part of the NIH graduate partnership program at the Vaccine Research Center testing passive immunization of rhesus macaques against SIV as a model for HIV. His current work aims to understand antibody responses that target both pathogens and gut commensal microbes. This work aims to elucidate the conditions necessary for eliciting broad, potent and durable vaccine responses.
Harrison OJ, Linehan JL, Shih HY, Bouladoux N, Han SJ, Smelkinson M, Sen SK, Byrd AL, Enamorado M, Yao C, Tamoutounour S, Van Laethem F, Hurabielle C, Collins N, Paun A, Salcedo R, O'Shea JJ, Belkaid Y. Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury. Science. 2019 Jan 4;363(6422).
Linehan JL, Harrison OJ, Han SJ, Byrd AL, Vujkovic-Cvijin I, Villarino AV, Sen SK, Shaik J, Smelkinson M, Tamoutounour S, Collins N, Bouladoux N, Dzutsev A, Rosshart SP, Arbuckle JH, Wang CR, Kristie TM, Rehermann B, Trinchieri G, Brenchley JM, O'Shea JJ, Belkaid Y. Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair. Cell. 2018 Feb 8;172(4):784-796.
Han SJ, Glatman Zaretsky A, Andrade-Oliveira V, Collins N, Dzutsev A, Shaik J, Morais da Fonseca D, Harrison OJ, Tamoutounour S, Byrd AL, Smelkinson M, Bouladoux N, Bliska JB, Brenchley JM, Brodsky IE, Belkaid Y. White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection. Immunity. 2017 Dec 19;47(6):1154-1168.
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.
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.