Zafar K. Khan

Zafar K. Khan

Professor, Microbiology and Immunology
Director, Center for International Translational Research

Ph.D.,1977, Banaras Hindu University, Varanasi, India

245 N. 15th Street
Mail Stop 1013A, Room 18311
Philadelphia, PA 19102
Tel: 215-762-3719
Fax: 215-762-1955
Email: zkhan@drexelmed.edu

Keywords:

Human T cell leukemia virus type 1 (HTLV-1), oncoprotein Tax, Animal model of HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP), Neuroinflammation, Demyelination, HIV-1, Microbicides

Research Interests:

For many years our frontier area of research has been on the microbial pathogenesis and therapy of infectious diseases including retroviruses and opportunistic infections. The current research efforts primarily focus on defining the mechanism of virus-induced neuroinflammation and demyelination in the central and peripheral nervous system in order to identify potential diagnostic markers and targets for the therapeutic intervention. The model pathogen under

study is human T cell leukemia virus type 1 (HTLV-1) that causes both immune and nervous system diseases. HTLV-1 is a human retrovirus that infects more than 20 million people worldwide predominantly in tropical areas. HTLV-1, although first human retrovirus discovered, is a virus that has received far less attention tha HIV and many aspects of its immunological and molecular pathogenesis remain unresolved.

A spinal cord section stained with myelin-specific marker showing intense demyelination

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive debilitating neurological disorder. In many ways it resembles with multiple sclerosis, an autoimmune disease of the brain. The HTLV-1 transcriptional transactivator protein Tax is the oncogenic protein of the virus and performs a variety of functions both intracellularly and extracellularly. The

progression of HAM/TSP is suggested to be due, in part, to the ability of Tax to work as an extracellular effector molecule. Furthermore, a majority of the immune response (humoral and cell-mediated) in HAM/TSP patients is directed against Tax indicating that Tax is available for immune recognition. However, the mechanism of Tax cross-presentation and its direct role in neurodegeneration remained uncharacterized. We are interested in addressing these issues by using a mouse model of HTLV-1 infection and disease progression. Once an effective model has been established, it will be utilized to study the role of Tax and other viral factors as well as the components of host immune response that may play important roles in the pathogenic process. The knowledge gained may be directly linked to clinical application. Other areas of research interest are HIV-1 therapeutics and microbicide development.

Selected Research Publications:

Maheshwari, R. K., Khan, Z. K., Rhodes-Feuillette, A., Mahouy, G., Badiallet, G., and R. M. Friedman. Interferon inhibits Aspergillus fumigatus growth in mice: an activity against an extracellular infection. Journal of Interferon Research, 8: 35-44, 1988.

Kumar, A., Khan, S. I., Manglani, A., Khan, Z. K., and S. B. Katti. Synthesis and antifungal activity of 3'deoxyribonucleosides. Nucleosides and Nucleotides, 13: 1049-1058, 1994.

Khan, Z. K., Katiyar, R., Shukla, R., and A. Mathur. Cryptococcosis associated with HIV negative Indian patients and HIV positive Indian blood donors. International Journal of Medical Microbiology, 283: 360-374, 1996.

Khan, Z. K., Chowdhry, L., Gyanchandani, A., Goswami, M., Farooqui, N., and S. A. Ranade. Aspergillus fumigatus strains recovered from immunocompromised patients (ICP): subtyping of the strains by RAPD analysis. Biochemistry and Molecular Biology International, 46: 537-548, 1998.

Khan, Z. K. and R. Katiyar. Potent antifungal activity of garlic (Allium sativum L.) against experimental murine disseminated cryptococcosis. Pharmaceutical Biology, 38: 87-100, 2000.

Gyanchandani, A., Khan, Z. K., and S. C. Maitra. Arbortristosides modulate murine peritoneal macrophages for phagocytosis and intracellular killing of Candida albicans as evidenced by TEM studies. Pharmaceutical Biology, 38: 340-352, 2000.

Jain, P., Khan, Z. K., Bhattacharya, E., and S. A. Ranade. Variation in random amplified polymorphic DNA profiles specific to fluconazole-resistant and -sensitive strains of Candida albicans. Diagnostics Microbiology and Infectious Diseases, 41: 113-119, 2001.

Tandon V. K., Singh, R. V., Rai, S., Chhor, R. B., and Z. K. Khan. Synthesis and pharmacological studies of some 2-t-amino and 2,3-di-t-amino substituted 1,4-naphthoquinones and related compounds. Bolletin Chimica Farmaceutica, 141: 304-310, 2002.

Prabhakar Y.S., Jain, P., Khan, Z. K., Haq, W., and S.B. Katti. Synthesis and QSAR studies on the antifungal activity of 2,3,4-substituted thiazolidines. QSAR and Combinatorial Science, 22: 456-465, 2003.

Kampani, K., Quann, K., Ahuja, J., Wigdahl, B., Khan, Z. K., and P. Jain. A novel high throughput quantum dot-based fluorescence assay for quantitation of virus binding and attachment. Journal of Virological Methods, 141: 125-132, 2007.

Ahuja, J., Lepoutre, V., Wigdahl, B., Khan, Z. K., and P. Jain. Induction of proinflammatory cytokines by human T cell leukemia virus type 1 Tax protein as determined by multiplexed cytokine protein array analyses of human dendritic cells. Biomedicine and Pharmacotherapy, 61: 201-208, 2007.

Jain, P., Ahuja, J., Khan, Z. K., Shimizu, S., Meucci, O., Jennings, S., and B. Wigdahl. Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1. Journal of Leukocyte Biology, 82: 44-56, 2007.

Manuel, S., Rahman, S., Wigdahl, B., Khan, Z. K., and P. Jain. Dendritic cells in autoimmune diseases and neuroinflammatory disorders. Frontiers in Bioscience, 12: 4315-4335, 2007.

Pandya, D., Rahman, S., Wigdahl, B., Khan, Z. K., and P. Jain. New insights into the pathogenesis, diagnosis, and treatment of human T cell leukemia virus type 1-induced disease. Future Virology, 2: 481-493, 2007.

Jain, P., Mostoller, K., Flaig, K. E., Ahuja, J., Alefantis, T., Khan, Z. K., and B. Wigdahl. Identification of HTLV-1 Tax amino acid signals and cellular factors involved in secretion of the viral oncoprotein. Journal of Biological Chemistry, 282: 34581-34593, 2007.

Patents:

A process for the preparation of 7-bromo-1-phenyl-8-acetoamido-9H-pyrido (3,4-b) indoles, useful as antifungal agents. A. Agarwal, S.K. Agarwal, P.K. Shukla and Z.K. Khan. Patent # 1126/Del/92, 1992.

A process for the preparation of 6-bromo-5-nitro-1-substituted-9H-pyrido (3,4-b) indoles useful as antifungal agents. A. Agarwal, S.K. Agarwal, P.K. Shukla and Z.K. Khan. Patent # 1123/DEL/92, 1992.

A process for the preparation of 7-bromo-1-phenyl-8-methane sulfonamido-9H-pyrido (3,4-b) indoles useful as antifungal agents. A. Agarwal, S.K. Agarwal, P.K. Shukla and Z.K. Khan. Patent # 1127/DEL/92, 1992.

A process for the preparation of 5-bromo-6-methane sulfonamido-1-phenyl-9H-pyrido (3,4-b) indoles useful as antifungal agents. A. Agarwal, S.K. Agarwal, P.K. Shukla and Z.K. Khan. Patent # 019/DEL/93, 1993.

A process for the preparation of 6-acetamido-5-bromo-1-substituted-9H-pyrido (3,4-b) indoles, useful as antifungal agents. A. Agarwal, S.K. Agarwal, P.K. Shukla and Z.K. Khan. Patent # 018/DEL/93, 1993.

Isolation of bivittoside D from sea cucumber and activity thereof. Lakshmi V., K. Pandey, A. Saxena, K. P. Madhusudanan, M. N. Srivastava, Z. K. Khan, P. Jain, G. Gupta, and J. D. Dhar. US Patent # U015092-8, 2004.