research-id-hepatitisc

Department of Internal Medicine Research

Immune Evasion by Hepatitis C Infection


Jonathan Moorman, M.D., Ph.D.

Dr. Moorman's laboratory focuses on the role of the immune system in the pathogenesis of hepatitis C infection. The goal of this research is to elucidate the mechanisms by which hepatitis C can evade the immune system and in doing so induce the significant pathology that is observed in infected patients. An additional goal is the translational application of research findings to patient care. To this end, studies involving patients infected with hepatitis C as well as co-infected with HIV are ongoing.

Current projects

1.  The role of PD-1/PDL-1 and SOCS-1 in leading to immune exhaustion in the setting of chronic HCV infection

2.  B cell dysfunction during chronic HCV infection.

3.  The role of HCV core protein in immunomodulation by hepatitis C.

4.  HIV/HCV co-infection:  immune markers for progression.

Personnel:

Jonathan Moorman, M.D., Ph.D.
Zhi Q. Yao, M.D., Ph.D.

Zhi Ping Dong

Techniques employed:

Cell culture
PCR/RT-PCR
Immunoblotting/ELISA
Site-directed mutagenesis
Immunoprecipitation
Immunofluorescence
Flow Cytometry


Collaborators:


Deling Yin, M.D., Ph.D.

Alok Agrawal, Ph.D.

Marina Nunez, M.D., Ph.D. (Wake Forest University)

Kevin High, M.D. (Wake Forest University)

Tamara Musgrave, M.D. (Pikeville Medical Center)

Funding:

NIH/NIAID R15

PI:  Jonathan Moorman, M.D., Ph.D.

“The Role of PD-1 and SOCS-1 in regulating T cell responses in HCV infection”

The objective of this study is to examine immunomodulatory signaling cascades altering T cell responses in chronically infected hepatitis C patients.

Recent Publications:

Yao Z, Prayther D, Trabue C, Dong Z, Moorman J.  Differential regulation of SOCS signaling in B and T lymphocytes by hepatitis C core protein.  Immunology (in press).  

Singh S, Suresh M, Prayther D, Moorman J, Rusinol A, Agrawal A.  C-reactive protein-bound, enzymatically-modified low-density lipoprotein does not transform macrophages in foam cells.  J Immunology (in press). 

Zhang Y, Woodruff M, Zhang Y, Miao J, Hanley G, Stuart C, Zeng X, Prabhakar S, Moorman J, Zhao B, Yin D. Toll-like receptor 4 mediates chronic restraint stress-induced immune suppression. J. Neuroimmunol. 2008 Jan 11; [Epub ahead of print]

Yao Z,  King E, Prayther D, Yin D, Moorman J.  T cell dysfunction by HCV core protein involves PD-1/PDL-1 signaling.  Viral Immunology 2007; 20(2): 276-287.

King E, Trabue C, Yin D, Yao Z, Moorman J.  Hepatitis C:  the Complications of Immune Dysfunction.  Expert Opinion in Clinical Immunology 2007; 3(2): 145-157. 

Yin D, Zhang Y, Stuart C, Miao J, Zhang Y, Li C, Zeng X, Hanley G, Moorman J, Yao Z, Woodruff M.  Chronic restraint stress modulates expression of genes in murine spleen.  J Neuroimmunol 2006; 177:11-17.

Moorman JP, Hepatitis C and the lung:  implications for therapy.  Chest 2005; 128:2882-2892.

Moorman JP, Fitzgerald SM, Prayther D, Lee S, Chi DS, Krishnaswamy G.  Induction of p38 MAPK-dependent IL-8 expression in NHLF fibroblasts by soluble hepatitis C core protein.  Respiratory Research 2005; 6:105.