Announcing the 2020 PLRC Pilot and Feasibility Awardees
Andres Duarte-Rojo, MD, DSc – Associate Professor, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition
“Cardiopulmonary exercise testing for cardiac risk and frailty assessment in liver transplant candidates”
Patients undergoing liver transplantation (LT) have a high risk for cardiovascular disease, including coronary artery disease and cirrhotic cardiomyopathy – a form of heart failure specific to cirrhosis. Frailty is a frequent condition among LT candidates. Together, cardiac disease and frailty are major causes of morbidity and mortality before and after LT. Conventional methods to diagnose and predict cardiovascular disease in LT candidates lack sensitivity and clinically relevant application. However, cardiopulmonary exercise testing (CPET) can assess coronary artery disease, cardiomyopathy, and frailty. Such versatility of CPET has caused it to become the standard of care in many transplant centers outside of the United States. In preliminary work that will be used to fund a more definitive study (RO1), we plan to investigate coronary artery disease, cirrhotic cardiomyopathy, and frailty in LT candidates, both by existing standard of care methods and CPET. LT candidates will be invited to participate, and CPET will be performed on a recumbent cycle ergometer, taking patients to maximal exercise. Respiratory rate, oxygen consumption, carbon dioxide production, heart rate, blood pressure and electrocardiogram will be continuously monitored during the test. We will compare agreement between tests used to diagnose coronary artery disease (CPET vs. cardiac stress testing), cirrhotic cardiomyopathy (CPET vs. dobutamine stress echocardiogram), and frailty (CPET vs. liver frailty index and 6-minute walk tests). We plan on including 75 LT candidates. We expect our results to improve our capacity to assess and prognosticate cardiovascular disease and frailty in LT, ultimately changing practice.
Akshata Moghe, MD, PhD – Chief Gastroenterology Fellow, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition
“The role of mTOR inhibition in β-catenin-mutated hepatocellular carcinoma”
Samer Tohme, Complex General Surgical Oncology and HPB Fellow, Department of Surgery
“The Role of Neutrophil Extracellular Traps in Promoting the Progression of Metastases after Liver Ischemia-Reperfusion”
Bokai Zhu, PhD – Assistant Professor, Department of Medicine, Division of Endocrinology and Metabolism
“Hepatic 12h-to-24h reprogramming drives NAFLD”
Carla Ng, PhD – Assistant Professor, Civil and Environmental Engineering
Stacy Wendell, PhD – Assistant Professor, Pharmacology and Chemical Biology
“Investigating the impacts of an emerging PFAS contaminant, Nafion-BP2, on liver metabolism”
Non-alcoholic fatty liver disease (NAFLD) affects 20-30% of the population in Western countries and is the number one cause of liver disease in children. In addition to contributors such as obesity and metabolic syndrome there is growing concern that chronic exposure to environmental toxicants such as per- and polyfluorinated alkyl acids (PFAA) contribute to liver disease. PFAA are highly persistent toxicants that have been detected in more than 99% of the US population and have been associated with markers of liver injury in exposed populations. Due to the growing concern for their long half-lives and association with a variety of disease pathologies, long chain PFAA, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have been replaced by a variety of per- and polyfluorinated alkyl ethers (PFAEs). Although intended to be safe replacements, there is now a growing body of evidence that these less studied compounds are also toxic and bioaccumulative. The co-PIs will combine their expertise in the biological fate and toxicokinetics of perfluorinated substances and on lipidomic and metabolomic analysis of toxicant impact to investigate whether PFAE replacements of long-chain PFAAs promote similar types and extent of liver injury. This proposal will focus on a particular PFAE, Nafion By-Product 2 (NBP2), recently discovered in the blood of residents living near a facility where it was used to replace long-chain PFAAs in fluoropolymer synthesis. We believe that NBP2 will be just as deleterious as PFOS, a PFAA of similar fluorinated chain length, in contributing to liver injury. We will test this hypothesis through complementary aims that will provide both discovery data sets and mechanistic insight into NBP2 signaling actions. Completion of this project will provide critical insight into the toxicological implications of ongoing exposure to NBP2. More broadly, our results will provide insight into the biological actions of PFAE with a goal of establishing structure-based modes of action for diverse PFAA and PFAE structures related to liver disease.
Pilot and Feasibility Grants
Pilot and Feasibility Grants fund new initiatives and/or support new investigators who are pursuing liver-related research that should lead to R01-type funding or other extramural support at a later date. These awards are for one year, and they provide support for investigators to collect preliminary data sufficient to support a future extramural grant application for independent research and/or to test a novel hypothesis. They are not intended for bridge funding, large projects by established investigators, or supporting or supplementing the ongoing funded research of an investigator.
- Track 1 (N). Junior investigators without independent grant support (excluding career development awards) seeking to establish independence in the field of liver research. **This category of applicant will be given preference.**
- Track 2 (EN). Established investigators with independent grant support—past or present—who have not been involved in liver research and who wish to develop new research directions related to the liver.
- Track 3 (E). Established investigators working in liver-related research who wish to begin a new project representing a major departure from their previous NIH-funded research.
Coulter Program – PLRC Joint Awards
The mission of this grant is to provide awardees with the means to develop a viable path to commercialization via a license to an existing commercial entity or the initiation of a startup company through Pitt’s Innovation Institute. The Award is aimed at developing the commercial potential of healthcare solutions that are based on innovative technologies related to liver health, including disease diagnosis, surgery, treatment, and public health. Projects may be medical devices, diagnostics, healthcare IT/software or drug delivery systems.