Crystal Wang

All Publications

• Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin AIDS RESEARCH AND HUMAN RETROVIRUSES Petersen, T., Lee, Y., Osinusi, A., Amorosa, V. K., Wang, C., Kang, M., Matining, R., Zhang, X., Dou, D., Umbleja, T., Kottilil, S., Peters, M. G. 2016; 32 (7): 660-667

  Abstract

  A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500 mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ.

  View details for DOI 10.1089/aid.2015.0236

  View details for Web of Science ID 000379609100007

  View details for PubMedID 26974581

  View details for PubMedCentralID PMC4931749

• International Collaborative Research Partnerships: Blending Science with Management and Diplomacy. Journal of AIDS & clinical research Lau, C. Y., Wang, C., Orsega, S., Tramont, E. C., Koita, O., Polis, M. A., Siddiqui, S. 2014; 5 (12)

  Abstract

  As globalization progressively connects and impacts the health of people across the world, collaborative research partnerships provide mutual advantages by sharing knowledge and resources to address locally and globally relevant scientific and public health questions. Partnerships undertaken for scientific research are similar to business collaborations in that they require attention to partner systems, whether local, international, political, academic, or non-academic. Scientists, like diplomats or entrepreneurs, are representatives of their field, culture, and country and become obligatory agents in health diplomacy. This role significantly influences current and future collaborations with not only the immediate partner but with other in country partners as well. Research partnerships need continuous evaluation of the collaboration's productivity, perspectives of all partners, and desired outcomes for success to avoid engaging in "research tourism", particularly in developing regions. International engagement is a cornerstone in addressing the impact of infectious diseases globally. Global partnerships are strategically aligned with national, partner and global health priorities and may be based on specific requests for assistance from the partnering country governments. Here we share experiences from select research collaborations to highlight principles that we have found key in building long-term relationships with collaborators and in meeting the aim to address scientific questions relevant to the host country and strategic global health initiatives.

  View details for DOI 10.4172/2155-6113.1000385

  View details for PubMedID 26225217

  View details for PubMedCentralID PMC4516384

• High interferon-stimulated gene ISG-15 expression affects HCV treatment outcome in patients co-infected with HIV and HCV JOURNAL OF MEDICAL VIROLOGY Katsounas, A., Hubbard, J. J., Wang, C. H., Zhang, X., Dou, D., Shivakumar, B., Winter, S., Schlaak, J. F., Lempicki, R. A., Masur, H., Polis, M., Kottilil, S., Osinusi, A. 2013; 85 (6): 959-963

  Abstract

  Increased baseline expression and lack of induction of interferon-stimulated genes (ISG) are strong negative predictors of therapeutic response to PegIFN/RBV in patients co-infected with HIV and hepatitis C virus (HCV). This study specifically addressed whether ISG-15 expression influences therapeutic responses in 20 HIV/HCV genotype-1 subjects undergoing HCV treatment. Non-responders had significantly higher baseline expression and selective induction of ISG-15 after IFN-α treatment relative to participants with sustained virological response. High baseline levels of ISG-15 were also associated with less induction of ISG with treatment. These results support a role for ISG-15 as a prognostic indicator and resistance factor to IFN-α.

  View details for DOI 10.1002/jmv.23576

  View details for Web of Science ID 000317906300004

  View details for PubMedID 23588721