Liver disease has emerged as a major source of morbidity and mortality in the United States with a disproportionate representation in some identifiable groups. Furthermore, unique management and treatment issues are associated with "special populations". This K-24 application demonstrates the candidate's focus on mentorship that is needed to develop the next generation of investigators who can perform patient-oriented research in populations with viral hepatitis and HIV infection. The etiologies of progressive liver disease are multifactorial and include viral hepatitis, drug toxicities including those associated with highly active antiretroviral therapies (HAART), alcohol, and variable levels of immunosuppression. Evidence is provided that the candidate is well equipped to provide mentorship of junior faculty and trainees within the context of his programmatic goals. This proposal includes a) Description of the candidate's commitment to patient-oriented research b) Characterization of key aspects of a mentorship program that incorporates elements of didactic training, involvement of trainees and junior faculty in ongoing research activities, and ongoing interaction between candidate and mentee to develop nascent patient based research careers .c) Review of the specific research activities funded by NIH and the pharmaceutical industry that serve as a structural framework for patient-oriented research. These experiences include all aspects of study design, statistical and data management, research ethics, research patient management, analysis, and publication. Most mentees are introduced to advanced laboratory techniques that utilize patient-derived samples in an effort to merge bed and bench experiences.
Liver disease is an important cause of morbidity and mortality in those with HIV infection. Research into pathobiologic mechanisms and study of treatment interventions is critical to future management paradigms. This grant serves as a vehicle to train the next generation of researchers in the context of an active patient-oriented research agenda focused on these issues.
|Mehta, Minesh; Hetta, Helal F; Abdel-Hameed, Enass A et al. (2016) Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients. Arch Virol 161:3161-9|
|Abdel-Hameed, Enass A; Rouster, Susan D; Zhang, Xiang et al. (2016) Characterization of HCV NS3 Protease Variants in HCV/HIV Coinfected Patients by Ultra-deep Sequence Analysis: Relationship to Hepatic Fibrosis. J Acquir Immune Defic Syndr :|
|Sherman, K E; Ke, R; Rouster, S D et al. (2016) Viral dynamic modelling of Hepatitis C and resistance-associated variants in haemophiliacs. Haemophilia 22:543-8|
|Sherman, Amy C; Sherman, Kenneth E (2015) Extrahepatic manifestations of hepatitis C infection: navigating CHASM. Curr HIV/AIDS Rep 12:353-61|
|Hetta, Helal F; Mekky, Mohamed A; Khalil, Nasr K et al. (2015) Association of colonic regulatory T cells with hepatitis C virus pathogenesis and liver pathology. J Gastroenterol Hepatol 30:1543-51|
|Lin, M V; Charlton, A N; Rouster, S D et al. (2014) Hepatitis C virus NS3 mutations in haemophiliacs. Haemophilia 20:659-65|
|Abdel-Hameed, Enass A; Ji, Hong; Sherman, Kenneth E et al. (2014) Epigenetic modification of FOXP3 in patients with chronic HIV infection. J Acquir Immune Defic Syndr 65:19-26|
|Schmidt, Warren N; Nelson, David R; Pawlotsky, Jean-Michel et al. (2014) Direct-acting antiviral agents and the path to interferon independence. Clin Gastroenterol Hepatol 12:728-37|
|Shata, Mohamed Tarek M; Abdel-Hameed, Enass A; Hetta, Helal F et al. (2013) Immune activation in HIV/HCV-infected patients is associated with low-level expression of liver expressed antimicrobial peptide-2 (LEAP-2). J Clin Pathol 66:967-75|
|Sulkowski, Mark S; Sherman, Kenneth E; Dieterich, Douglas T et al. (2013) Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann Intern Med 159:86-96|
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