Donald J. Alcendor, Ph.D.
Assistant Professor of Cancer Biology, Meharry Medical College
Associate Professor Health Disparities and HIV, Meharry Medical College
Adjunct Associate Professor of Cancer Biology at Vanderbilt University School of Medicine
Meharry Medical College
1005 Dr. D.B. Todd, Jr., Blvd.
Nashville, TN 37208
Antiretroviral therapy (ART) has reduced the incidence of Kaposi’s sarcoma (KS) in developed western countries. However, 95% of the estimated 40 to 60 million people infected with HIV have no access to these drugs. HIV/AIDS-associated KS is still a significant problem in the U.S. among individuals who are noncompliant due to toxicities and those who progress to AIDS without receiving drug therapy. KS is cause by Kaposi’s sarcoma-associated herpesvirus (KSHV) and is characterized as an angioproliferative tumor of vascular endothelial cells and produces rare B cell lymphoproliferative diseases in the form of pleural effusion lymphomas (PEL) and some forms of Multicentric Castleman’s Disease (MCD). Only 1-5% of cells in KS lesions actively support lytic replication of KSHV, and it is clear that cellular factors must interact with viral factors in the process of oncogenesis and tumor progression. Identifying novel host-factor determinants that contribute to KS pathology is essential for developing prognostic markers for tumor progression and metastasis as well as novel therapeutics for the treatment of KS.
Our studies thus far have shown that galectin-3, fibulin-2 and fibulin-5 are dysregulated genes in KSHV infected dermal microvascular endothelial cells (DMVEC). All of these genes are implicated in malignancy and most likely contribute to KS pathogenesis. Thus, we are interested in evaluating galectin-3, fibulin-2, and fibulin-5 in order to determine their usefulness as diagnostic markers for KS tumor progression/metastasis, and whether they would serve as a target(s) for a novel treatment strategy.
Our hypothesis is that downregulation of galectin-3, fibulin-2 and fibulin-5 contributes to KS pathogenesis and tumorigenesis, and that modulation of their expression in the tumor microenvironment could serve to either alter virus replication and/or reduce tumor angiogenesis, progression and metastasis. Thus reconstitution or over-expression of these genes in KS tissue and AIDS-associated pleural effusion lymphomas (PELs) could alter and/or reduce viral pathogenesis associated with KS and hence serve as molecular targets for therapeutic interventions.
- Ahsen R. Chaudhry, Knobel S.M., Ladson G. and Alcendor DJ.. Expression of fibulins in vaginal epithelium from women of diverse ethnicity: Implication for racial disparities in stress urinary incontinence ( to be submitted ). 2010.
- Alcendor D.J., Charest A. M, Knobel S.M., and Zhu WQ.. Infection and upregulation of proinflammatory cytokines in brain vascular by human cytomegalovirus ( in revision ). 2010.
- Alcendor D.J., Knobel S. Desai P, Zhu W.Q., Vigil H.E., and Hayward G.S.. KSHV downregulation of galectin-3 in kaposi's sarcoma. Glycobiology. 2010; 20: 521-32.
- Alcendor D.J., Zhu W.Q., and Desai P.. KSHV Downregulation of Fibulins in Kaposi's sarcoma: Implications for tumorigenesis ( to be submitted). 2010.
- Dual labeled Immunohistochemistry in Kaposi's Sarcoma. J. Vis. Exp ( in press ). 2010.
- Hayward, G.S, Alcendor DJ., and Boger RA. In Viral Oncology: Basic Science and Clinical Applications (Book). The Role of KSHV in Pathogenesis of Kaposis Sarcoma: Jeang KT and K.Kalili eds. 2010; Ver: 377-407.
- Marrs C.N., Zhu W.Q, Sweet S., Alcendor D.J.. Evidence for Gardnerella Vaginalis uptake and internalization by squamous vaginal epithelial cells: Implications for the phathogenesis of bacterial vaginosis ( in revision ). 2010.
- Alcendor D.J., Zong J.C., Dolan A., Davidson A., and Hayward G.S.. Patterns of divergence in the rapidly evolving vCXC and vGPCR gene clusters in primate cytomegalovirus genomes. Virology. 2009; 365: 21-32.
- Hildreth J.E.K., and Alcendor, D.. Mayo Clinic HIV eCurriculum Series: In Essentials of HIV medicine. Mayo Clinic Foundation for Medical Education and Research. 2009; 1-20.
- Alcendor, D. J, and Hayward G. S.. "Cytomegalovirus (Herpesviridae) Simian Cytomegaloviruses ". In Encyclopedia of Virology. 2008; 3rd ed.
- D.J., Zong R. Arav-Boger, Alcendor, D.J, and Hayward G.S.,. Reflections on the interpretations of heterogeneity and strain differences based on very limited PCR sequence data from Kaposiï¿½s sarcoma associated herpesvirus. A review. J. Clin. 2007; 40:: 1-8.
- Davison, A.J., Dolan, A., Akter, P., Addison, C., Dargan, D.J., Alcendor, D.J, McGeoch, D.J., and Hayward, G.S.. The Human Cytomegalovirus Genome Revisited: Comparison with the chimpanzee cytomegalovirus genome. J Gen Virol. 2003; 84:: 17-28.
- Arav-Boger, R., Willoughby, R.F., Pass, R.F., Zong, J-C., Jang, W.J., Alcendor, D.J, and Hayward, G.S.. Polymorphisms of the cytomegalovirus-encoded TNFÎ± and Î²-chemokine receptors in congenital CMV disease. J. Inf. Dis. 2002; 186: 1057-64.
- Chiou, C.J., Poole, L.J., Kim, P.S., Ciufo, D.M., Cannon, J.S., ap Rhys, C.J., Zong, J.-C., Alcendor, D.J, Ambinder, R.F., and Hayward, G.S.. Patterns of gene expression and a transactivation function exhibited by the vGCR (ORF74) chemokine receptor protein of Kaposiï¿½s sarcoma-associated herpesvirus. J. Virol. 2002; 76: 3421-39.
- Alcendor, D. J, and Hayward G. S.. Index of Viruses: "Cytomegalovirus Betaherpesviridae". In Springer Verlag. 2001; 1st ed.: 156-62.
- Wu, F., Ahn, J-H., Alcendor, D.J, Jang W-J., Xiao, J., Hayward, S.D., Hayward, G.S.. Origin independent assembly of sarcoma-associated herpesvirus (KSHV) DNA replication compartments in transient co-transfection assays and association with the ORF-K8 protein and cellular PML (PODs). J. Virol. 2001; 75: 1487-506.
- Alcendor, D. J, and Hayward G. S.. Animal Cytomegalovirus (Herpesviridae). In Encyclopedia of Virology. 1999; 2nd ed.: 357-63.
- Poole, L., Zong, J-C., Ciufo, D.M., Alcendor, D.J, Cannon, J.S. Ambinder, R.F., Orenstein, J.M., Reitz, M.S. and Hayward, G.S. Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposis sarcoma associated herpesvirus (HHV8) reveals evidence for recombinant and for two distinct types of ORF-K15 alleles at the right hand end. J. Virol. 1999; 73:: 6646-60.
- Richman K.L., Montali R. J., Garber R. L., Kennedy M.L., Lehnhardt, J., Hildebrandt T., Schmitt D., Alcendor, D.J, and Hayward G. S.. Novel endotheliotropic herpesviruses fatal for asian and african elephants. Science. 1999; 5405:: 1171-6.
- Zong, JC, Ciufo DM, Alcendor, D.J, Wan X, Nicholas J, Browning P, Rady P, Orenstein JM, Rabkin C, Su IJ and GS Hayward. High level variability in the ORF-K1 membrane protein gene at the left end of the kaposis sarcoma associated herpesvirus genome defines four major virus subtypes and multiple variant or clades in different human populations. J. Virol. 1999; 73:: 4156-70.
- Nicholas, J.Zong, Alcendor, D.J, Ciufo, D, Poole, L. J, Sarisky, R.T, Chiou, C. J, Zhang, X, Wan, X, Guo, H., G., Reitz, and Hayward G.S. Novel organizational features, captured cellular genes, and strain variability within the genome of KSHV/HHV8. JNCI. 1998; 23:: 79-88.
- Micheals, MG, Alcendor, D.J, St. George, K, Rinaldo, Jr., Ehrlich, G.D, Becich, M.J, and Hayward G. S.. Distinguishing baboon cytomegalovirus from human cytomegalovirus: Importance for xenotransplantation. J. Inf. Dis. 1997; 176:: 1476-83.
- Barry, PA, Alcendor, D.J, Power, MD, kerr, H, and Luciw PA. Nucleotide sequence and molecular analysis of the rhesus cytomegalovirus immediate-early gene and the UL121-117 open reading frame. Virology. 1996; 215:: 61-72.
- Alcendor, D.J., Chapman GD, Beaman BL. Isolation, sequencing and expression of the superoxide dismutase-encoding gene (sod) of Nocardia asteroides strain GUH-2. Gene. 1995; 164:: 143-5.
- Alcendor, D.J., Barry P.A, Pratt-Lowe E, Luciw PA. Analysis of the rhesus cytomegalovirus immediate early gene promoter. Virology. 1993; 194:: 815-21.
- Alcendor, D.J.. Structure and function of the rhesus cytomegalovirus immediate early gene. Dissertation. 1992; ((University of California, Davis)).
- Barry, P.A., Pratt-Lowe, E., Alcendor, D.J., E. Unger, and Paul Luciw. Molecular interactions between human immunodeficiency virus type I and human cytomegalovirus Ann. New York Acad. 1990; 616:: 54-63.
- Barry, P.A., Pratt-Lowe, E., Unger, R.E., Marthas, M., Acendor, D.J., and Luciw, P.A.. Molecularinteractions of rhesus cytomegalovirus and the human and simian immunodeficiency viruses. J.Med. Primatol. 1990; 19:: 327-37.