Pilot and Feasibility Program
The program will support innovative new projects that explore the feasibility of novel, testable concepts and enhance the digestive and liver disease research scope following the themes of the center. The program specifically supports junior faculty, faculty new to digestive and liver disease research, women and underrepresented minorities engaged in cross-disciplinary research.
All academic full-time faculty—including instructors, faculty research scientists and assistant professors—who are eligible to apply as a principal investigator for extramural National Institutes of Health (NIH) R01 funding and who are affiliated with Cedars-Sinai Medical Center are eligible to apply for a Cedars-Sinai Digestive Diseases Research Center (CSDDRC) Pilot and Feasibility Program grant. Applicants may fall into any of the following three categories based on NIH guidelines:
New investigators (as defined by NIH guidelines) without independent extramural grant support (including federal, R01, R00, U01, P01, DoD, VA merit or equivalent, and excluding career-development awards, such as K, AGA, AASLD, ALF, and Crohn's and Colitis Foundation of America) who seek to establish independence in the field of gastrointestinal (GI), liver and pancreatic disease research.
Established investigators with independent grant support—past or present—who wish to develop a new research direction related to GI, liver and pancreatic disease research.
Established investigators working in research related to GI, liver and pancreatic disease who wish to start a new project representing a major departure from their previous NIH or other federally funded research. New collaborative research between a CSDDRC investigator and a non-CSDDRC investigator would be eligible under this category.
In the fall of 2020, the CSDDRC announced its first Pilot and Feasibility Program funding opportunity, and one project was selected for funding (provided by the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai). Below is a summary of this project.
Targeting FGFR1/2 Signaling in Cholestatic Liver Diseases
Nirmala Mavila, PhD, assistant professor of Medicine, Karsh Division of Gastroenterology and Hepatology
$25,000 for one year (Jan. 1, 2021-Dec. 31, 2021)
Chronic cholestatic liver disorder (CLD) is a life-threatening liver disease if left untreated. CLD affects all age groups, including infants and adults. The most common CLDs are primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC) and biliary atresia (BA), which exclusively affects infants. The clinical characteristics of CLDs include an aggressive form of inflammation-driven biliary fibrosis that initiates with chronic injury to the biliary epithelial cells (BECs). The progression of biliary fibrosis is associated with a dynamic epithelial-to-mesenchymal cell interaction in the portal area consisting of BECs, portal fibroblasts, hepatic stellate cells and immune cells. In advanced stages of CLD, biliary fibrosis leads to bridging fibrosis, which connects multiple portal tracts and leads to a significant loss of hepatic function. Despite extensive investigation for decades, the molecular and cellular mechanisms of bridging fibrosis in CLD are not well understood. Previously, Dr. Mavila identified activation of fibroblast growth factor receptor (FGFR) and transforming growth factor (TGF) beta signaling co-localization to a heterogeneous population of progenitor cells in experimental and human BA livers. The goal of this project is to elucidate the role of FGFR1/2-TGFbeta crosstalk in progenitor cells and how it contributes to the rapidly progressing bridging fibrosis of CLD.
Nirmala Mavila was able to generate additional preliminary data using the funding and submitted an R01, which was assigned to the National Institute of Diabetes and Digestive and Kidney Diseases and just received a score of 10th percentile in March 2022.