The Reinecker laboratory has a long standing interest in basic mechanisms controlling the mucosal immune system, intestinal barrier function and Inflammatory Bowel Diseases (IBD). Dr. Reinecker is an Associate Professor of Medicine at Harvard Medical School and an Associate Immunologist at MGH. Dr. Reinecker is the Director of the Genetics, Genomics and Molecular Biology Core of the Center for the Study of Inflammatory Bowel Diseases (CSIBD) at MGH and the Director for Information Systems for the Division of Gastroenterology at MGH. Current research interests focus on the mechanisms of IBD susceptibility genes in the regulation of the mucosal subspecifications of antigen processing cells for microbial recognition in the intestine. The laboratory has expertise in biochemical and cell biological methods and applies molecular biological approaches to the characterization of the mucosal immune system with particular focus on mechanisms of macrophage and dendritic cell innate immune function. Recently, Dr. Reinecker has developed novel 3D and 4D imaging approaches to study membrane trafficking, antigen uptake and cell migration in the mucosal immune system. Many of Dr. Reinecker's post doctoral fellows have gone on to establish their own laboratories studying different aspects of epithelial cell biology and mucosal immunology.
Dr. Hans-Christian Reinecker
Associate Professor of Medicine
Harvard Medical School
Director Genetics, Genomics and Molecular Biology Core, CSIBD
Massachusetts General Hospital
Jackson bldg. R711
Boston MA 02114
Email: firstname.lastname@example.org; email@example.com
Bayasi Guleng, PhD, Postdoctoral Research Fellow
Graduate School of Medicine, University of Tokyo
Current Position: Professor of Medicine, Medical College of Xiamen University, Xiamen City, China
Carmen Alonso Cotoner, MD, Postdoctoral Research Fellow
Current Position: Faculty in Medicine, Institut de Recerca, Hospital Universitari Vall d’Hebron, Digestive Diseases Research Unit, Department of Gastroenterology, Barcelona, Spain
Sonal Gupta, MD, PhD, Postdoctoral Research Fellow
University of Bradford, United Kingdom
Seiji Arihiro, MD, PhD, Postdoctoral Research Fellow
Jikei University School of Medicine
Current position: Asst. in Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan
Atsuko Fukazawa, MD, Postdoctoral Research Fellow
Current position: Surgeon, Hamamatsu School of Medicine, Hamamatsu, Japan
Current position: Physician, Department of Internal Medicine,
Universitätsklinikum Ulm, Ulm, Germany
Mitsue Shimada MD, PhD, Postdoctoral Research Fellow
Current position: Physician, Department of Internal Medicine, Shiga Hospital, Japan
Kiyotaka Kurachi, MD, Postdoctoral Research Fellow
Current position: GI Surgeon, Hamamatsu School of Medicine, Japan
Takanori Sakaguchi, MD, PhD, Postdoctoral Research Fellow
Current position: Surgeon, Hamamatsu School of Medicine, Japan
Stephan Brand, MD, Postdoctoral Research Fellow
Current position: German Research Society, University Hospital Munich-Grosshadern, Department of Medicine II
Andreas Muellhofer, MD, Postdoctoral Research Fellow
Current position: Asst. in Medicine, Katharinehospital, Stuttgart, Germany
Kerstin Luedtke-Heckenkamp, MD, Postdoctoral Research Fellow
Current position: Asst. in Medicine, Kreiskrankenhaus, Marienhoehe, Abt. Geriatrie, Wuerselen, Germany
Tetsushi Kinugasa, MD, Postdoctoral Research Fellow
Current position: Asst. in Surgery, Fukuoka University School of Medicine, Japan
Pietro G. Andres, MD, Postdoctoral Research Fellow
Current Position: Senior Clinical Fellow in Gastroenterology, UC San Francisco, CA, HHMI Fellowship
Masaaki Awane, MD, Postdoctoral Research Fellow
Current position: Asst. in GI Surgery, Kyoto University Hospital, Japan
Raisuke Nishiyama, MD, Postdoctoral Research Fellow
Current position: Chief of GI surgery Hamamatsu-Kita Hospital, Japan
Unravel the genetic basis of Inflammatory Bowel Diseases (IBD)
The intestinal mucosa functions as an immunological organ, which plays a major role in the development of oral tolerance and the development of immunity. The defense response to microbiota in the lumen of the intestine is required to maintain health and to overcome disease. Crohn’s disease (CD) and ulcerative colitis (UC) are non-infectious, chronic and relapsing inflammatory diseases of the gastrointestinal tract characterized by injury to the barrier function of the intestine. This is the result of an exaggerated defense response to the intestinal microbiota leading to recurrent and long lasting episodes of diarrhea and abdominal pain. We study the function of newly discovered mediators of host defenses, which can regulate both inflammatory and inhibitory immune responses mediated by IBD-associated gene variants. The elucidation of the biology of these regulators will provide pivotal insights into the genetic basis of IBD. We aim to develop new insights into the reason for the enhanced immune responses and lack of their control in patients with inflammatory bowel diseases leading to chronic intestinal inflammation and delayed tissue repair.
Functional subspecifications of mucosal dendritic cells
Antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages are a diverse group of phagocytic cells that maintain tolerance and regulate adaptive immune responses. In the intestine, a combination of conventional DCs, migratory DCs and plasmacytoid-derived DCs form a surveillance system that is constantly engaged in sampling and processing of food antigens and commensal and pathogenic microbiota. This functional dichotomy poses unique challenges for the control of immune responses in the highly antigenic context of the intestine and the pivotal requirement to maintain intestinal barrier function. Consequently, DCs with distinct functional subspecifications have evolved in Peyer’s patches (PPs), mesenteric lymph nodes (MLNs) and the small intestine and colon in adaptation to different local environmental conditions However, the mechanism by which intestinal DCs control the mucosa specific adaptations of regulatory T cells (e.g., IL-10 secretion) and T helper cell function (e.g., induction of Th17 differentiation) is not well understood. Our studies will provide new insights into the region specific regulatory programs of DC systems in the large and small intestine for the control of adaptive immunity required for tissue repair in the highly antigenic environment of the intestine.
Signal transduction in innate immune regulation
These studies will provide new insights into the integration of innate immune activation pathways that are required for the recognition of microbiota at mucosal surfaces. In this project we directly address the mechanisms responsible for the recognition of microbial antigens and responses, which are a key area of importance for IBD research. Initial recognition of microbiota is mediated by pattern recognition receptors (PRRs) such as nucleotide binding oligomerization domain (NOD)-like receptors (NLRs), Toll-like receptors (TLRs), Rik and MDA5 receptors, which recognize conserved microbial structures known as pathogen associated molecular patterns (PAMPs). The combination of these signaling pathways controls innate immune responses to microbial effectors, which include the activation of NF-κB dependent proinflammatory mediators such as TNF-α, but also initiates signaling circuitry stimulating IL-10 expression to control inflammation. The definition of the coordination of these different microbial recognition pathways is required for the understanding of innate immune responses at mucosal interphases where a multitude of antigenic information needs to be distinguished. These studies currently focus on a new component of pathogen recognition by caspase-recruiting domain (CARD)-containing NOD-like receptors. Defining the functional role of this newly discovered central component of microbial pattern recognition will provide pivotal insights into the mechanisms that disrupt mucosa specific control of innate immune responses required for mucosal inflammation as well as tissue repair in IBD.
Development of new therapeutics for intestinal inflammation
A more precise definition of the mechanisms of microbial recognition is required for the development of specifically targeted approaches for the control of IBD. None of the currently available treatments specifically target the reason for the disruption of inflammatory or inhibitory regulation underlying the diverse and multifactoral diseases, which we recognize as IBD. Based on newly identified regulatory circuits we are developing approaches to directly enhance inhibitory immune regulation to microbial factors without disrupting mucosal defenses.
Microbiome and host interactions in the intestine
Mucosal DCs form a major surveillance system in the lamina propria of the small and large intestine and are constantly engaged in sampling and processing of food antigens, commensal bacteria and intestinal pathogens. Antigens must cross the intestinal epithelium in a controlled manner and processed by DCs, since bacteria or their products are a primary risk factor for the development of intestinal inflammation. Dysregulation of this immune modulation in response to food antigens or bacterial recognition leads to intestinal inflammation in animal models of human inflammatory bowel diseases such as CD, US and celiac disease. In the context of the intestine, DCs can differentiate in an organ-specific fashion in response to a spectrum of environmental and endogenous stimuli. We unravel the molecular mechanisms that define the function of intestine specific DC subsets in the interaction with the intestinal microbiome.
Development of new functional imaging approaches for the mucosal immune system
In vivo visualization of biological processes including imaging of cellular membrane trafficking at a molecular level as well as clinical imaging of disease mechanisms in tissues in patients has become essential components of basic and clinical metabolic research. Non-invasive visible light imaging is now a widely accepted technology allowing researchers to follow many biological processes in healthy and diseased animal models. We utilize 3D and 4D analysis of bioluminescence, e.g., luciferase-based and fluorescence-based imaging to study the mucosal immune system in vivo and in vitro. Highly sensitive EM CCD cameras with signal enhancement provide quantitative real time imaging of cell migration and cell interaction during antigen presentation and membrane trafficking in immune cell of the intestine. We develop mouse model systems to apply live cell molecular imaging including, confocal, spinning disk confocal, Fret, Frap and TIRF microscopy for in vitro and in vivo imaging of cellular processes from the tracking and integration of dendritic cell precursors into intestinal tissues to the study of receptor uptake and signal transduction.
We are currently looking for Postdoctoral Fellows with an interest in signal transduction and mucosal immunology.