Goals. Immediate and long-term objectives are: 1) to be established as a leader in translational, clinical, and basic research related to liver disease;and 2) to train the next generation of physician-scientists working in gastrointestinal and liver disease. 1 am committed to enhancing the educational training of medical students, residents, fellows, and junior faculty members in research and facilitate the growth of patient-oriented research. Research Project. In this application, 1 have included two patient-oriented research projects that stem from my current HCV Center Grant and an ROl grant using the Virahep-C cohort. These two distinct, well-characterized cohorts are included to demonstrate the variety of research that would be available for future trainees. The central goal of our research is to understand the immune factors that govern recovery from HCV infection, either spontaneously or therapy-induced. The purpose ofthe new research proposed here is to answer additional questions that have arisen in the course of carrying out the funded projects. Development plan. To date, the majority of individuals I have mentored (11 of 12) have pursued academic careers. Support from this K24 will release me from clinical and administrative responsibilities and allow me to mentor of more trainees and explore the many collaborative opportunities within the outstanding scientific community at UCHSC. Research environment. The studies outlined in this proposal will be performed in Dr. Rosen's lab, 2,707 sq ft on the 10th floor of UCDs Research Complex 2. The laboratory contains biohazard laminar flow hoods, cell culture C02 incubators, inverted and upright upright microscopes, containment centrifuges, -70 C and liquid nitrogen freezers, and standard PCR equipment. The lab also houses a FACS Aria, Luminex system, and an AID automated ELISPOT reader. Adjacent space is available for molecular biology and protein expression work. A wide variety of shared equipment is available through the Gl Division and the Colorado Center for AIDs Research (CFAR), including flow cytometers and cell sorters (Flow Cytometry Core), high speed and ultracentrifuges, gamma and beta counters, cell harvesters, fluorescent microscope, FPLC, and automated ABI 377 sequencer.
. Approximately 200 million throughout the world have chronic HCV infection, and a large proportion of patients fail to respond to antiviral treatment. This K24 will enhance my ability to mentor junior investigators and will provide the groundwork for novel immunotherapeutic approaches of this common disease.
|Rosen, Hugo R; Golden-Mason, Lucy; Daly, Ann K et al. (2016) Variants in the LGALS9 Gene Are Associated With Development of Liver Disease in Heavy Consumers of Alcohol. Clin Gastroenterol Hepatol 14:762-8.e1|
|Biggins, S W; Gralla, J; Dodge, J L et al. (2014) Survival benefit of repeat liver transplantation in the United States: a serial MELD analysis by hepatitis C status and donor risk index. Am J Transplant 14:2588-94|
|McMahan, Rachel H; Wang, Xiaoxin X; Cheng, Lin Ling et al. (2013) Bile acid receptor activation modulates hepatic monocyte activity and improves nonalcoholic fatty liver disease. J Biol Chem 288:11761-70|
|Biggins, Scott W; Trotter, James; Gralla, Jane et al. (2013) Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation. J Hepatol 58:969-76|
|Stone, Amy E L; Giugliano, Silvia; Schnell, Gretja et al. (2013) Hepatitis C virus pathogen associated molecular pattern (PAMP) triggers production of lambda-interferons by human plasmacytoid dendritic cells. PLoS Pathog 9:e1003316|
|Golden-Mason, Lucy; McMahan, Rachel H; Strong, Michael et al. (2013) Galectin-9 functionally impairs natural killer cells in humans and mice. J Virol 87:4835-45|
|Rosen, Hugo R (2013) Emerging concepts in immunity to hepatitis C virus infection. J Clin Invest 123:4121-30|
|Biggins, Scott W; Bambha, Kiran M; Terrault, Norah A et al. (2012) Projected future increase in aging hepatitis C virus-infected liver transplant candidates: a potential effect of hepatocellular carcinoma. Liver Transpl 18:1471-8|
|Golden-Mason, Lucy; Stone, Amy E L; Bambha, Kiran M et al. (2012) Race- and gender-related variation in natural killer p46 expression associated with differential anti-hepatitis C virus immunity. Hepatology 56:1214-22|
|McMahan, Rachel H; Golden-Mason, Lucy; Nishimura, Michael I et al. (2010) Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity. J Clin Invest 120:4546-57|
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