Dr. Moss is a junior investigator in Inflammatory Bowel Disease (IBD). As a fellow he trained in the molecular biology of inflammation, in addition to his clinical training as a gastroenterologist. In the last 2 years he has been mentored by Dr Simon Robson in immunology research methods. His immediate goal is to further develop his immunology and research training in translational research in order to investigate the role of endogenous immuno-suppressive pathways in IBD. The development of future diagnostic and therapeutic tools for patients with these diseases will require investigators who can bring advances in immunology to the bed-side, and vice versa. His medium- term goal is to acquire suitable preliminary data for a successful R01-application in this field, and establish his reputation through relevant scholarly activities. In the long-term Dr Moss intends to obtain consistent funding to maintain an independent laboratory group focused on translational research in novel therapeutics and diagnostic methods in IBD. The research career development plan for this K23 is based on a combination of an outstanding mentor in immunology (Dr Simon Robson), a Career Development Committee of investigators with strong translational research resumes, and specific coursework tailored to foster Dr Moss's pathway to independence. The host institution (BIDMC) have demonstrated their on-going commitment to Dr Moss through his promotion to junior faculty and Assistant Professor, the continued provision of laboratory space, protected research time (salary support), and dedicated mentorship for him. The Dept of Medicine and Division of Gastroenterology have limited his clinical workload with the primary intention of allowing him appropriate time for laboratory experience, coursework and academic networking. The proposed project is not only a topic of profound clinical importance but also an ideal training vehicle in which Dr Moss will have the opportunity to solidify his existing skills and to learn new research techniques. The purpose of this K23 proposal by Dr Alan Moss is to examine the mechanisms through which one pathway of immune regulation is altered in patients with Crohn's disease, and how certain treatments modify this effect. In particular, this proposal will study a group of enzymes (CD39, CD73) and receptors that convert harmful products of tissue damage (ATP, ADP) to immuno- suppressive molecules (adenosine). Studies in animal models have suggested that these enzymes are protective against inflammation, but their role in human Crohn's disease is unknown. Preliminary data by Dr Moss has observed an alteration in the proportion and activity of these enzymes in patients with Crohn's disease. The experiments in this proposal will quantify the presence and activity of these purinergic pathways in patients with Crohn's disease, and healthy controls. We will examine how inflammatory states may impair their action, and how treatment with certain drugs (anti- TNF agents) modifies their activity. This project aims to provide a thorough understanding of these pathways in patients with Crohn's disease, so that novel treatments may be developed to enhance their immuno-suppressive roles.

Public Health Relevance

Inflammatory Bowel Disease affects nearly 2 million Americans. This proposal will improve our understanding of regulation of the immune system in patients with Crohn's disease. It may provide novel targets for drug treatments for patients with this condition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK084338-04
Application #
8637061
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2011-05-01
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
4
Fiscal Year
2014
Total Cost
$146,148
Indirect Cost
$10,648
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Vaughn, Byron P; Vatanen, Tommi; Allegretti, Jessica R et al. (2016) Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease. Inflamm Bowel Dis 22:2182-90
Mitsuhashi, Shuji; Feldbrügge, Linda; Csizmadia, Eva et al. (2016) Luminal Extracellular Vesicles (EVs) in Inflammatory Bowel Disease (IBD) Exhibit Proinflammatory Effects on Epithelial Cells and Macrophages. Inflamm Bowel Dis 22:1587-95
Gubatan, John; Mitsuhashi, Shuji; Zenlea, Talia et al. (2016) Low Serum Vitamin D During Remission Increases Risk of Clinical Relapse in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol :
Abhyankar, Anita; Moss, Alan C (2015) Iron Replacement in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Inflamm Bowel Dis 21:1976-81
Longhi, Maria Serena; Moss, Alan; Bai, Aiping et al. (2014) Characterization of human CD39+ Th17 cells with suppressor activity and modulation in inflammatory bowel disease. PLoS One 9:e87956
Devlen, Jennifer; Beusterien, Kathleen; Yen, Linnette et al. (2014) The burden of inflammatory bowel disease: a patient-reported qualitative analysis and development of a conceptual model. Inflamm Bowel Dis 20:545-52
Franquet, Elisa; Palmer, Mathew R; Gifford, Anne E et al. (2014) Rifaximin suppresses background intestinal 18F-FDG uptake on PET/CT scans. Nucl Med Commun 35:1026-31
Moss, Alan C; Lillis, Yvonne; Edwards George, Jessica B et al. (2014) Attitudes to mesalamine questionnaire: a novel tool to predict mesalamine nonadherence in patients with IBD. Am J Gastroenterol 109:1850-5
Bai, Aiping; Moss, Alan; Kokkotou, Efi et al. (2014) CD39 and CD161 modulate Th17 responses in Crohn's disease. J Immunol 193:3366-77
Ham, Maggie; Longhi, Maria S; Lahiff, Conor et al. (2014) Vitamin D levels in adults with Crohn's disease are responsive to disease activity and treatment. Inflamm Bowel Dis 20:856-60

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