A Novel Sources of Enteric Neurogenisis During Both Embryogenesis and In the Adult
Fellow: Wael El-Nachef, MD
PI: Marianne Bronner, PhD, Chair, Division of Biology at the California Institute of Technology
Dr. El-Nachef is research fellow in the lab of Dr. Marianne Bronner, who is studying novel sources of enteric neurogenesis both during embryogenesis and in the adult. Recently, so-called "Schwann cell precursors" (SCPs) have been suggested to contribute up to one-fifth of the neurons in the murine colon, but little is known about the origin or the spatiotemporal dynamics of this phenomenon. Using the zebrafish animal model, we will employ transgenic tools, lipophilic dyes, and retroviral reporters to investigate SCP-like cells in the intestine. The UCLA DDD seed grant will enable us to perform transcriptome analysis on these novel neuronal precursors, which will provide key information regarding their identity and potentially the mechanisms underlying their migration, proliferation, and differentiation. Better understanding enteric neurogenesis could lead to new therapies for enteric neuropathies and irritable bowel syndrome. Advance Care Planning For Patients with Decompensated Cirrhosis. Recently, so-called "Schwann cell precursors" (SCPs) have been suggested to contribute up to one-fifth of the neurons in the murine colon, but little is known about the origin or the spatiotemporal dynamics of this phenomenon. Using the zebrafish animal model, we will employ transgenic tools, lipophilic dyes, and retroviral reporters to investigate SCP-like cells in the intestine. The UCLA DDD seed grant will enable us to perform transcriptome analysis on these novel neuronal precursors, which will provide key information regarding their identity and potentially the mechanisms underlying their migration, proliferation, and differentiation. Better understanding enteric neurogenesis could lead to new therapies for enteric neuropathies and irritable bowel syndrome.
Oral Presentation: A population of phox2b-expressing cells arises independently of pre-existing enteric neuronal precursors in the post-colonized intestine, as revealed by in vivo time-lapse imaging of zebrafish embryos; El-Nachef WN and Bronner M ENS; 5th International Symposium, Boston, MA (April 2018). Awarded an NIH travel grant for this presentation.
Poster Presentation: Phox2b-positive cells arise independently of pre-existing enteric neuronal precursors in the post-colonized gut, as revealed by live time-lapse imaging of zebrafish embryos; El-Nachef WN and Bronner M; Digestive Disease Week (DDW), Washington, DC (June 2018). Awarded "Poster of Distinction."
Association Between Esophageal Dysfunction and Lung Severity in Patients with Systemic Sclerosis
Fellow: David Lin, MD
Mentor/PI: Jeffrey L. Conklin, MD, Medical Director, Center for Esophageal Disorders, Director, Gastointestinal Motor Function Laboratory
Systemic sclerosis (SSc) is a heterogeneous, multisystem, autoimmune-mediated connective tissue disorder. Gastrointestinal involvement, including reflux and esophageal dysmotility, can be seen in up to 90% of patients, and it is the leading cause of morbidity. Lung involvement, manifested as idiopathic pulmonary fibrosis and pulmonary arterial hypertension, is the most common cause of mortality. It is unknown what role esophageal dysmotility and reflux play in the development of lung dysfunction. Our aims are to assess the association between esophageal dysfunction and lung severity in scleroderma patients. We will perform a retrospective study of a large cohort of scleroderma patients in a tertiary care referral center. Esophageal metrics will include esophageal manometry, pH testing, and esophagogastroduodenoscopy findings. These will be correlated with surrogates of pulmonary severity including pulmonary function testing and chest CT scoring systems. We hope this study will better elucidate the association between esophageal dysfunction and pulmonary involvement, which may have prognostic value and help guide clinical management.
Pilot Study Using Oral Capsule Fecal Microbiota Transplantation to Decolonize Gastrointestinal Carbapenem-Resistent Enterobacteriaceae
Fellow: Lisa Lin, MD, MS
PI: Zachary Rubin, MD, Assistant Professor, Infectious Diseases, UCLA
Currently, there is no known effective treatment for gastrointestinal carriage of carbapenem-resistant enterobacteriaceae (CRE), which is associated with poor outcomes. The study is a single-center, open-label, controlled, prospective cohort pilot study that aims to evaluate the efficacy and safety of using oral capsule fecal microbiota transplantation (FMT) to decolonize gastrointestinal CRE. Subjects will be adult outpatients with a known history of positive CRE result on a previous clinical culture with fecal carriage of CRE verified at time of enrollment. Subjects will be followed prospectively and monitored for adverse events and clearance of fecal CRE carriage at one week and one month after oral capsule FMT. Subjects who decline oral capsule FMT can choose the alternative of being in the control arm, where stool cultures at one week and one month will be taken to assess the rate of spontaneous gastrointestinal CRE clearance. The long-term goal of the project is to expand patients’ limited treatment options for this condition. If this pilot study demonstrates oral capsule FMT to be a safe and effective treatment, it would pave the way for a larger randomized controlled trial to be conducted in the future. It would also lead to the establishment of a novel application of FMT and benefit patients by preventing future CRE-related infections and morbidities.
What Else to Know About Hepatitis C and Hepatocellular Carcinoma and Direct Acting Antivirals
Fellow: Kelvin Nguyen, MD
Mentors: Sammy Saab, MD, MPH, Head of Outcomes Research in Hepatology; Mohamed El Kabany, MD, Assistant Clinical Professor of Internal Medicine and Hepatology in Pfleger Liver Institute; Steven-Huy Han, MD, Director, Hepatology Clinical Research Center, Program Director, Transplant Hepatology Fellowship and Assistant Director, UCLA Asian Liver Center
Advance Care Planning For Patients with Decompensated Cirrhosis
Fellow: Arpan Patel, MD
PI: Anne Walling, MD, PhD, Assistant Professor, Division of General Internal Medicine and Health Services Research, UCLA and Palliative Care, VA Greater Los Angeles Healthcare System
While liver transplantation has improved outcomes and survival for patients with decompensated liver disease, it still remains a condition associated with extremely high morbidity and mortality. There have been few studies examining how often and how well healthcare teams are successful in preparing patients with cirrhosis for such catastrophic health events, given that they are so likely. This is a qualitative study that will examine the process of advance care planning in patients with decompensated liver disease treated at three major liver transplant centers in Los Angeles: UCLA, Cedars-Sinai, and USC-Keck. We will perform semi-structured interviews with both patients with liver disease and members of the liver healthcare teams, including transplant hepatologists, hepatobiliary surgeons, nurse practitioners, social workers, and case managers. The goals will be to understand how often advance care planning successfully occurs in this patient population and what patient-level, provider-level, and system-level factors may play a role in this process. We hope this research will open the door to new research questions that will further explore how goals of care discussions and advance directives can fit in the overall care of patients with chronic liver disease. We also hope that this project will be helpful in informing quality improvement initiatives at these institutions.
Understanding Perceptions and Stages of Change for Diagnostic Colonoscopy in Patients with Positive Fecal Immunochemical Testing
Fellow: Christine Yu, MD
PI: Folasade P. May, MD, PhD, MPhil, Core Investigator at the VA HSR&D Center for Study of Healthcare Innovation, Implementation & Policy, Co-Director, Global Health Education Program, UCLA Center for World Health, and Assistant Professor of Medicine in the Vatche and Tamar Manoukiand Division of Digestive Diseases
Fecal immunochemical testing (FIT) is one of the recommended modalities for colorectal cancer (CRC) screening and is typically followed by diagnostic colonoscopy if positive; however, follow-up diagnostic colonoscopy rates are subpar. In integrated health systems, approximately half of patients with positive FIT results undergo diagnostic colonoscopy. The aim of our study is to identify and rank fallout points along the clinical care process map from positive FIT to diagnostic colonoscopy. We will perform a retrospective review of patients from a tertiary care integrated health system age 50 to 75 with average CRC risk and at least one positive FIT from 2015-2017. Demographic and clinical factors will include physician notification of results, appropriate referrals for diagnostic colonoscopy and scheduling and procedure completion by manual electronic medical record abstraction. We hope to utilize these findings in designing future, more targeted interventions to improve diagnostic colonoscopy rates after positive FIT.