Gary C Chan, PhD

Current Appointments

• Assistant Professor of Microbiology and Immunology

Hospital Campus

• Downtown

Education & Fellowships

• Fellowship: Louisiana State University Health Science Center, 2011, Microbiology and Immunology
• PhD: University of Alberta, Canada, 2005, Medical Microbiology and Immunology
• BS: University of Alberta, Canada, 1999, Microbiology

Publications

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Research Abstract

Human cytomegalovirus (HCMV), a betaherpesvirus, is endemic throughout the world with seropositivity reaching 50 to 80% among urban populations in the United States.  HCMV infection is generally asymptomatically in immunocompetent individuals, although HCMV is now believed to be a primary viral candidate in the etiology of several diseases including atherosclerosis, inflammatory bowel disease and glioblastomamultiforme.  In immunocompromised individuals such as neonates, AID patients and transplant recipients, HCMV infection can lead to multiorgan failure resulting in significant morbidity and mortality.  The myriad of organ diseases associated with HCMV infection is a direct pathological consequence of the systemic viral spread to and infection of multiple organ sites that occurs during either asymptomatic or symptomatic infections, which is necessary for the establishment of viral persistence within the infected host.

HCMV infection is characterized by a monocyte-associated viremia prior to the onset of viral pathogenesis, suggesting that HCMV may utilize these blood sentinels as vehicles to mediate hematogenous dissemination of the virus to several organ sites.  In support, monocytes are the primary cell type infected in the blood during acute HCMV infection and are the predominant infiltrating cell type found in infected organs.  However, despite monocytes being “at the right place, at the right time”, these cells have a short life span of approximately 2 days and are not permissive for viral replication.  To overcome this biological quandary, we have recently shown HCMV infection to stimulate differentiation of short-lived, viral replication non-permissive monocytes into long-lived, viral replication permissive macrophages, which, to our knowledge, is the only identified viral pathogen that can directly induce the monocyte-to-macrophage differentiation process. Moreover, we have demonstrated that HCMV-differentiated macrophages possess unique biological characteristics not associated with a “prototypical” macrophage, suggesting that the virus may have evolved a distinct mechanism to regulate the myeloid survival/differentiation process.  Currently, our laboratory is focused on determining the molecular mechanisms of how HCMV uniquely modulates the cellular differentiation machinery in the absence of viral gene products, in order to orchestrate the survival and differentiation of monocytes following infection.

Selected Publications:

1.    Nogalski, M.T., Chan, G., Stevenson, E.V. and Yurochko, A.D.  HCMV-activation of monocyte integrin/src signalling pathway regulates paxillin activity linking virus-induced cellular motility to virus entry.  J. Virol.  85:1360-1369 (2010) 

2.    Chan, G., Nogalski, M.T., Bentz, G.L., Smith, M.S., Paramater, A. and Yurochko, A.D.  Phosphatidylinositol 3-kinase-dependent upregulation of Mcl-1 by human cytomegalovirus is mediated by epidermal growth factor receptor and inhibits apoptosis in short-lived monocytes.  J. Immunol. 184:3213-3222 (2010)

3.    Chan, G., Nogalski, M.T., and Yurochko, A.D.  Activation of epidermal growth factor receptor on monocytes is required for human cytomegalovirus entry and mediates cellular motility.  Proc. Natl. Acad. Sci. USA 106: 22369-22374 (2009)

4.    Chaudhuri, S., Lowen, B., Chan, G., Davey, A., and Guilbert, L.J.  Human cytomegalovirus interacts with toll-like receptor 2 and CD14 on syncytiotrophoblasts to stimulate expression of tumour necrosis factor-alpha mRNA and apoptosis.  Placenta 30: 994-1001 (2009)

5.    Chan, G., Bivins-Smith, E.R., Smith, M.S. and Yurochko, A.D.  NF-κB and phosphatidylinositol 3-kinase activity mediates the unique HCMV-induced M1/M2 polarization of monocytes.  Virus Res. 144: 329-333 (2009)

6.    Chan, G., Bivins-Smith, E.R., Smith, M.S., Smith, P.M., and Yurochko, A.D.  Transcriptome analysis reveals human cytomegalovirus reprograms monocytes towards a M1 macrophage.  J. Immunol. 181: 698-711 (2008)

7.    Chan, G., Bivins-Smith, E.R., Smith, M.S., and Yurochko, A.D.  Transcriptome analysis of NF-κB- and phosphatidylinositol 3-kinase-regulated genes in human cytomegalovirus infected monocytes.  J. Virol. 82: 1040-1046 (2008)

8.    Smith, M.S., Bivins, E.R., Bentz, G.L., Chan, G., Minard, J., and Yurochko, A.D.  HCMV infection of monocytes requires the rapid induction of phosphatidylinositol 3-kinase- and NF-κB-dependent signalling to upregulate adhesion to and migration through the endothelium.  J. Virol. 81: 7683-7694 (2007)

9.    Bentz, G.L., Jarquin-Pardo, M., Chan, G., Smith, M.S., and Yurochko, A.D.  HCMV infection of endothelial cells promotes naïve monocyte diapedesis by altering adhesion receptor protein and tight and adherens junction protein expression.  J. Virol. 80: 11539-11555 (2006)

10.  Chan, G. and Guilbert, L.J.  Ultraviolet-inactivated human cytomegalovirus induces placental syncytiotrophoblast apoptosis in a toll-like receptor-2 and tumour necrosis factor-α dependent manner.  J. Pathol. 210: 111-120 (2006)

11.  Johnstone, E.D., Chan, G., Sibley, C.P. and Guilbert, L.J.  Sphingosine -1-phosphate inhibition of trophoblast differentiation though a Gi-protein coupled response.  J. Lipid Res. 48: 1833-1839 (2005)

12.  Chan, G. and Guilbert, L.J.  Enhanced monocyte binding to human cytomegalovirus infected syncytiotrophoblast results in increased apoptosis via the release of tumour necrosis factor-α.  J. Pathol. 207: 462-470 (2005)

13.  Johnstone, E.D., Mackova, M., Das, S., Payne, S.G., Lowen, B., Sibley, C.P., Chan, G. and Guilbert, L.J.  Multiple anti-apoptotic pathways stimulated by epidermal growth factor in cytotrophoblast.  Placenta 26: 548-555 (2005)

14.  Chan, G., Stinski, M.S. and Guilbert, L.J.  Human cytomegalovirus-induced upregulation of intercellular cell adhesion molecule-1 on villous syncytiotrophoblasts.  Biol. Reprod. 71: 797-803 (2004)

15.  Chan, G., Hemmings, D.G., Yurochko, A.D. and Guilbert, L.J.  Human cytomegalovirus-caused damage to placental trophoblasts mediated by immediate-early gene-induced tumour necrosis factor-α.  Amer. J. Pathol. 161: 1371-1381 (2002)