Antivirals, Bioinformatics, Cancer, Gene Regulation, Hepatitis C Virus, Interferon Resistance, Liver, RNA, Viruses and Virology
Genetics and Genomic Sciences [GGS], Microbiology [MIC]
BS, The University of Michigan
MS, The University of California
PhD, The Rockefeller University
, The Rockefeller University
, The Rockefeller University
Rockefeller University Graduate Fellowship
Steinhaus Memorial Teaching Award
Public Health Service Traineeship
B. HCV creates a genome-length, double-stranded RNA
HCV establishes persistent infection despite triggering a robust interferon-induced anti-viral response. Interferon-based regimens as well as direct-acting antiviral (DAA) drugs are used to treat HCV. Regardless of the regimen, HCV RNA can be undetectable in blood for months only to reappear after treatment ends, causing relapse. Using a novel approach, we found that HCV dsRNA is the predominant form of viral RNA in the liver of HCV-infected patients. HCV can respond to IFN by producing a genome-length viral dsRNA. This dsRNA is a key target of ribavirin. The development of DAAs that target viral dsRNA might improve treatment for HCV and other viruses.
D. Analysis of portal blood and other compartments in HCV-positive patients undergoing liver transplantation
We are in a unique position to collaborate with many different divisions in the Mount Sinai Hospital to obtain tissue from HCV-positive patients undergoing liver transplantation. Our objectives are to measure intrahepatic HCV dsRNA levels, degree of fibrosis, intrahepatic leukocyte populations, and portal vein blood cell populations and cytokines. We are in the process of studying the effect of the innate immune system on liver disease.
A. Minicores: a new family of HCV core protein isoforms
In experimental systems, we previously discovered a new family of HCV core protein isoforms called minicores (Eng et al., JVI, 2009) that lack the N-terminus of p21 core. We have recently found that HCV minicores are released into patients’ blood. Additionally, cells cultured in human serum secrete large quantities of minicores through a process that is not dependent on infectious virion production. The low density of secreted minicores indicates that they may be part of lipoviroparticles. Experiments are underway to investigate the biological effects of secreted minicores.
C. Clinical outcomes of HCV treatments
We have a strong clinical team that studies real-world outcomes of new direct acting antiviral (DAA) drugs against hepatitis C virus (HCV). New DAAs for HCV are receiving FDA approval and entering clinical practice at a rapid pace, replacing interferon-based therapies with less toxic and more effective regimens that allow a much higher percentage of patients to achieve a sustained virological response (SVR), the positive outcome of HCV treatment. Health care providers need information about how these new medications perform in real world clinical practice. We analyze the short- and long-term impact of new HCV regimens on liver-related outcomes.
E. Optimizing vitamin D treatment in HIV/AIDS
In the post-HAART era, patients continue to suffer from the adverse medical consequences of HIV/AIDS. The adverse effects include incomplete immune reconstitution, chronic inflammation, depression, increased risk of cardiovascular and metabolic disease, and low bone density. Clinical trials suggest that vitamin D supplements can increase bone density, reduce inflammation, alleviate depression, and increase longevity if given in adequate doses. The project will yield a validated protocol for treating vitamin D deficiency in HIV- infected patients on HAART and will provide initial data about the risks and health benefits of vitamin D and calcium supplements.
Ge X, Antoine DJ, Lu Y, Arriazu E, Leung TM, Klepper AL, Branch AD, Fiel MI, Nieto N. High Mobility Group Box-1 (HMGB1) Participates in the Pathogenesis of Alcoholic Liver Disease (ALD). The Journal of biological chemistry 2014 Aug; 289(33).
Crismale JF, Martel-Laferrière V, Bichoupan K, Schonfeld E, Pappas A, Wyatt C, Odin JA, Liu LU, Schiano TD, Perumalswami PV, Bansal M, Dieterich DT, Branch AD. Diabetes mellitus and advanced liver fibrosis are risk factors for severe anaemia during telaprevir-based triple therapy. Liver international : official journal of the International Association for the Study of the Liver 2014 Aug; 34(7).
Bichoupan K, Martel-Laferriere V, Sachs D, Ng M, Schonfeld EA, Pappas A, Crismale J, Stivala A, Khaitova V, Gardenier D, Linderman M, Perumalswami PV, Schiano TD, Odin JA, Liu L, Moskowitz AJ, Dieterich DT, Branch AD. Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response. Hepatology (Baltimore, Md.) 2014 Jul;.
Martel-Laferrière V, Brinkley S, Bichoupan K, Posner S, Stivala A, Perumalswami P, Schiano T, Sulkowski M, Dieterich D, Branch A. Virological response rates for telaprevir-based hepatitis C triple therapy in patients with and without HIV coinfection. HIV medicine 2014 Feb; 15(2).
Branch AD, Barin B, Rahman A, Stock P, Schiano TD. Vitamin D status of human immunodeficiency virus-positive patients with advanced liver disease enrolled in the solid organ transplantation in HIV: multi-site study. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2014 Feb; 20(2).
Branch AD, Kang M, Hollabaugh K, Wyatt CM, Chung RT, Glesby MJ. In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use. The American journal of clinical nutrition 2013 Aug; 98(2).
Branch AD. HCV in 2011: ebb tide, or the gathering storm?. Seminars in liver disease 2011 Nov; 31(4).
Gutierrez JA, Klepper AL, Garber J, Walewski JL, Bateman K, Khaitova V, Syder A, Tscherne DM, Gauthier A, Jefferson D, Rice CM, Schiano TD, Branch AD. Cross-genotypic polyclonal anti-HCV antibodies from human ascitic fluid. Journal of virological methods 2011 Jan; 171(1).
Branch AD, Rice CM. Antisense gets a grip on miR-122 in chimpanzees. Science translational medicine 2010 Jan; 2(13).
Eng FJ, Walewski JL, Klepper AL, Fishman SL, Desai SM, McMullan LK, Evans MJ, Rice CM, Branch AD. Internal initiation stimulates production of p8 minicore, a member of a newly discovered family of hepatitis C virus core protein isoforms. Journal of virology 2009 Apr; 83(7).
Branch AD, Stump DD, Gutierrez JA, Eng F, Walewski JL. The hepatitis C virus alternate reading frame (ARF) and its family of novel products: the alternate reading frame protein/F-protein, the double-frameshift protein, and others. Seminars in liver disease 2005 Feb; 25(1).
Branch A. Hepatitis C Virus Codes for Proteins and Replicates: Does It also Trigger the Interferon Response?. Seminars in Liver Disease 2000; 20: 57-68.
Branch A. A Good Antisense Molecule Is Hard to Find. Trends in Biochemical Sciences 1998; 23: 45-50.
Branch A, Robertson HD. Efficient trans cleavage and a common structural motif for the ribozymes of the human hepatitis delta agent. Natl. Acad. Sci., U. S. A. 1991; 88: 10163-10167.
Branch A, Benenfeld BJ, Baroudy BM, Wells FV, Gerin JL, Robertson HD. An ultraviolet-sensitive RNA structural element in a viroid-like domain of the hepatitis delta virus. Science 1986; 243: 649-652.
Branch A, Robertson HD. A replication cycle for viroids and other small infectious RNA's. Science 1984; 223: 450-455.
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Below are financial relationships with industry reported by Dr. Branch during 2015 and/or 2016. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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