There is a rich history of clinical research discovery at Boston Medical Center. The Boston Bowel Preparation Scale (BBPS; pronounced “bee-bops”) was developed by investigators in the Gastroenterology Section to provide a standardized method for rating the quality of bowel preparation during colonoscopy. The BBPS is now considered an international standard for assessing bowel cleanliness. Investigators at Boston Medical Center, led by Dr. Paul C. Schroy, Emeritus Professor of Medicine at Boston University School of Medicine, have made significant contributions to our understanding colorectal cancer screening and surveillance. Dr. Schroy’s most recent research activities have focused primarily on the development, implementation and evaluation of model programs for community-based colorectal cancer control, including: (1) exploring the role of shared decision-making as a strategy for increasing patient participation in colorectal cancer screening; (2) better defining the epidemiology of colorectal neoplasia and the development of risk assessment tools for predicting the presence of advanced neoplasia at screening colonoscopy; (3) evaluating the feasibility and validity of novel colorectal cancer screening strategies such as stool-based DNA testing and virtual colonoscopy; (4) implementation of quality measures related to colorectal cancer screening; and (5) developing strategies to reduce the public health burden of early-onset colorectal cancer. In addition to his own independent research activities, Dr. Schroy has also mentored numerous medical students, residents, fellows and junior faculty, many of whom have pursued careers in academic gastroenterology.
Clinical research efforts in Hepatology include using non-invasive methods to predict the development of cirrhosis complications and studying Hepatitis C virus and HIV co-infection.
Advancing excellence in medical education is central to the mission of the Gastroenterology Section at Boston Medical Center. Faculty at Boston Medical Center are working to advance training in endoscopy at multiple levels. Many education projects focus on using the state-of-the-art endoscopy simulation lab where trainees can learn both basic and advanced endoscopic techniques. Drs. Wasan and Huang have also developed an innovative “Teach the Teacher” curricula after systematically studying best practices in endoscopic education. Beyond endoscopic training, Dr. Wasan also studies novel ways to teach core gastroenterology topics to both housestaff and Gastroenterology Trainees.
Nonalcoholic Fatty Liver Disease Research Center:
The Boston Medical Center NAFLD Research Center’s mission is to perform novel, multi-disciplinary clinical and translational research in the area of NAFLD. Our patient-centered research program is dedicated to improving the diagnosis and assessment of liver disease in addition to identifying new therapies and treatments to halt the progression of disease. The NAFLD research program, which includes research assistants, trainees, nurses, clinicians, and scientists is led by Dr. Michelle T. Long, MD, MSc, a nationally recognized leader in NAFLD.
Boston Medical Center-based Research: The NAFLD research program at Boston Medical Center is multi-disciplinary and includes collaborators within Gastroenterology/Hepatology, Endocrinology, Obesity Medicine, Nutrition, and Bariatric Surgery as a part of the Metabolic Disease Research Program at Boston University School of Medicine. We offer Phase II and III Clinical Trials and are actively enrolling patients. In 2020 we received a research grant to leverage informatics to identify high risk patients with NAFLD across Boston Medical Center. We are also beginning a collaboration with the Boston Medical Center Teaching Kitchen, Rooftop Farm, and Preventive Food Pantry. The NAFLD research program actively collaborates with basic and translational scientists at Boston University (Medical and Charles River Campus) and the University of California San Diego NAFLD Research Center. Boston Medical Center also collaborates with NASHNET.
Framingham Heart Study-based Research: Dr. Long also leads the adiposity research efforts in the Framingham Heart Study where she has been an ancillary study Principal Investigator since 2015. Through funding from the National Institutes of Health, Boston University, Doris Duke Charitable Foundation, Gilead Sciences, and Echosens Corporation Dr. Long is building a NAFLD-research program integrated into the longitudinal, multi-generational Framingham Heart Study. The aims of the FHS-NAFLD research program are targeted at identifying novel tools to identify patients at risk for liver fibrosis due to NAFLD, uncover new biomarkers of disease and to understand the relationship between NAFLD and cardiovascular disease. The ultimate goal is to leverage the rich data resource of the Framingham Heart Study to develop a comprehensive map of NAFLD progression from gene to protein to metabolites to disease while accounting for clinical and environmental variation.
Crohn’s and Colitis Research Center
The Crohn’s and Colitis Research Center at Boston Medical Center is centered around patient-oriented clinical and translational research aimed at improving care for patients with inflammatory bowel diseases. Dr. Wasan and Moss run clinical research studies aimed at developing innovative approaches to improving the quality of health maintenance, understanding the response to vaccinations and illustrating healthcare disparities. The Crohn’s and Colitis Research Center also provides access to clinical trials of novel therapeutics as a site for multi-center, controlled trials. Our clinical team specializes in providing care to underserved populations. A major focus of our clinical research is on identifying and addressing barriers to effective health maintenance and high quality care. Innovative interventions that we study include collaboration with the Boston Medical Center Teaching Kitchen and Rooftop Farm. These studies have been funded by industry grants.
Our translational research program (PI:Moss) focuses on mucosal immunology in patient samples, specifically the correlation between mucosal cytokines and fecal exosomes. Dr. Moss is an internationally recognized expert in inflammatory bowel disease and mucosal immunology. His group led the first intervention study of microbial therapy to prevent recurrence of Crohn’s disease after surgery, which has led to related studies on microbial composition after ileal resection. These studies have been funded by NIDDK, Crohn’s & Colitis Foundation and Helmsley Charitable Trust. Collaborators include MIT Microbiome Research Center and start-ups in the microbiome space.
Basic and Translational Research
Gouon-Evans Laboratory: From Liver Development to Therapy for Liver Diseases
Dr. Gouon-Evans, Pharm.D., Ph.D., is a nationally recognized leader in the fields of liver development and regeneration through her pioneered work using the pluripotent stem cell system. Dr. Gouon-Evans leads the program of liver diseases and regeneration within the Center for Regenerative Medicine (CReM) where her lab is located. The Gouon-Evans lab investigates cellular and molecular mechanisms driving liver development, regeneration and cancer. We specifically interrogate the role of progenitor/stem cells and how they share similar molecular signature and functions during these 3 processes using the mouse model, the pluripotent stem cell (PSC) differentiation system and human liver specimens. Projects in the Gouon-Evans lab will lead to a better understanding of the liver development, to the establishment of multi-modular approaches for improving intrinsic liver regeneration and through transplantation of PSC derivatives; and will reveal the impact of specific cancer stem cells as a target for diagnosis and therapy in liver oncogenesis.
Role of adult liver progenitor cells in liver regeneration to treat acute and chronic such as NAFLD liver diseases: Liver transplantation is currently the only cure for acute and chronic liver failure, but the shortage of liver donors presents a critical challenge. A promising alternative solution to liver transplantation is the activation of existing and/or facultative liver progenitor cells (LPCs) in vivo. Although the liver has a robust ability to self-regenerate by proliferation of mature hepatocytes and cholangiocytes, in the case of acute or chronic liver injury, proliferation of mature cells is exhausted. Liver repair in most acute and chronic liver diseases in human is thus associated with expansion of LPCs in a process termed ductular reaction that is thought to contribute to liver regeneration. Several human liver diseases have been modeled in rodents, in which LPCs display progenitor features in vitro and to some extent a regenerative ability in vivo. These studies raise the exciting idea that forced activation of LPCs in sick livers will accelerate intrinsic liver regeneration. We are currently establishing tools to stimulate LPCs to promote liver repair.
Directed differentiation of human induced pluripotent stem cell (hiPSC) towards functional human hepatocyte-like cells for cell therapy in acute and chronic liver diseases: The use of hiPSC differentiation cultures to generate functional hepatocyte-like cells (HLC) for cell therapy of liver diseases is still an ongoing challenge. Even though a growing literature has established efficient protocols to generate such cells in vitro, hiPSC-derived HLCs remain inefficient at repopulating diseased livers. Our research is focused on identifying and modulating molecular pathways required for successful liver cell mass repopulation following HLC transplantation into various liver deficient mouse models.
The Mostoslavsky Lab: Utilizing iPSC for Disease Modeling
The Mostoslavsky Lab is a basic science laboratory in the Section of Gastroenterology in the Department of Medicine at Boston University, affiliated with the Boston University Center for Regenerative Medicine (CReM). Our goal is to study human biology in normal and disease states, through the use of stem cells in general and pluripotent stem cells in particular, with two major focuses: gastrointestinal tract and immunity/inflammation. We believe that by discovering the mechanisms involved in stem cell self-renewal and differentiation we will be able to manipulate stem cell fate and use it as the basis for the correction of several diseases. Project areas in the lab focuses on the use of induced Pluripotent Stem (iPS) cells for modeling of intestinal, liver and neural diseases, as well as their differentiation towards immune relevant lineages. For a full description of projects please visit www.mostoslavskylab.com.
IPS CELL MODELING OF INTESTINAL DIFFERENTIATION
One major focus of the lab is the utilization of iPS Cells for the study of intestinal differentiation with a particular interest in Colorectal Carcinoma (CRC). For this purpose we have generated iPSC from individuals suffering from FAP and Lynch Syndrome, the two most highly penetrant hereditary forms of CRC (Sommer et al, PLoS One, 2018). We have recently established in the lab a novel robust differentiation protocol for the generation of proximal and distal Human Intestinal Organids (HIOs) in the absence of mesenchyme support (Mithal et al, Nat. Comm. 2020). By studying the earlier events associated with intestinal differentiation comparing the normal and mutant cells we aim at discovering the basic mechanisms involved in tumor development in the gastrointestinal tract.
IPS CELL MODELING OF HEPATIC DIFFERENTIATION
Several projects in the lab utilizes the liver differentiated progeny of iPSC to study genetic and infectious diseases affecting the liver. In collaboration with the BU NEIDL we are using iPSC-derived hepatocytes to study Ebola virus (EBOV) entry and replication. Utilizing RNA-sequencing we have recently discovered a unique inflammatory hepatic response elicited by EBOV. By accessing primary human target cells we hope to establish a new paradigm in the use of iPSC-derived cells for infectious diseases.