Breakthrough research starts with a good idea. Unfortunately, it is extremely difficult to secure research funding from the National Institutes of Health (NIH) and other major sources without preliminary findings to indicate that the idea has a good chance to succeed. Its'a a vicious circle - getting significant funding requires data, but obtaining the data requires funding. Seed grants break the impasse by providing the initial funding that enables researchers to investigate promising but untested ideas. By supportiing these projects, seed grants lead to much larger grants from the NIH and other funders.
The Joel and Barbara Marcus Research Seed Grants provide funds to UCLA's GI fellows in the Vatche and Tamar Manoukian Division of Digestive Diseases for just such a purpose - to conduct important studies in gastroenterology and hepatology for which alternative sources of funding are not readily available. These seed grants ensure that fellows have the opportunity to conduct high-quality research. The grants help to fund statistical services, laboratory assays, nursing support, and other research needs.
Following are the most recently funded projects among the division's fellows:
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 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.
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; Health Sciences Professor of Medicine, Vatch and Tamar Manoukian Division of Digestive Diseases
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.
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; 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