Mary Wallace Stanton Professor for Faculty Affairs
Professor, Molecular & Comparative Pathobiology, Neurology, Pathology and Joint Appointment Molecular Biology & Genetics
Graduate Program Affiliations:
- Biochemistry, Cell and Molecular Biology
- Cellular and Molecular Medicine
- Human Genetics
Background and Training
Dr. Clements received a PhD in 1973 in Biochemistry from the University of Maryland, College Park. She completed two post-doctoral research fellowships in the Departments of Molecular Biology and Genetics (1974-1976) with Dr. Bernard Weiss and in Neurology (1976-1978) with Dr. Richard Johnson providing training and expertise in molecular biology and virology. Dr. Clements trained in neurovirology and viral pathogenesis with Dr. Richard T. Johnson studying for the first time the animal lentiviruses and their role in chronic neurological diseases. She joined the faculty of the Department of Neurology as an Assistant Professor in 1979, and the faculty of the Division of Comparative Medicine in 1988.
Dr. Clements was the first Director of the Department of Comparative Medicine; the department had divisional status until 2002. Comparative Medicine, renamed the Department of Molecular and Comparative Pathobiology is an academic department with faculty involved in animal model research, teaching medical students, graduate students, clinical and research post-doctoral fellows.
Dr. Clements became the Director of Retrovirus Laboratory in 1992 providing leadership for 4 faculty in an integrated research program on the pathogenesis of lentivirus infections with emphasis on animal models of AIDS Dementia and central nervous system (CNS) disease. Dr. Clements has directed the training of 14 PhD and 2 M.S. students and 13 post-doctoral fellows.
Dr. Clements has served as Vice Dean for Faculty of the School of Medicine for Dean Edward Miller, M.D. from 1999 to the present.
Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, the simian immunodeficiency virus (SIV) is used to examine the molecular basis for the pathogenesis of HIV CNS disease. Research projects include studies of viral molecular genetics and host cell genes and proteins involved in the pathogenesis of disease. Further, studies of lentivirus infections of macrophages and specific viral pathogenesis in the central nervous system and the lung are of interest. These studies have led us to identify the viral genes that are important in neurovirulence of SIV and the development of CNS disease. The SIV Envelope gene and the NEF gene both play important roles in infection of the CNS. The mechanisms of the action of these proteins in the CNS are complex and are under investigation.
Our group was the first to identify the role of CD4-independent virus entry in the pathogenesis of neurological disease. We have shown that neurovirulent SIV can infect cells in a CD4-independent, CCR5 dependent manner in primary CNS endothelial cells and cell lines that express only CCR5. Further, studies have shown that the Nef protein from the neurovirulent virus interacts with different cellular kinases than the Nef protein from other strains of SIV. Our studies have demonstrated that replication of neurovirulent virus in vivo by quantitation of viral RNA copies in the brain and viral load in cerebral spinal fluid is directly correlated with the development of CNS lesions during SIV infection. Finally, we have shown that virus replication in the CNS is independently regulated from the peripheral blood. Because virus replication in the brain is mainly in macrophages while in the peripheral blood it occurs in lymphocytes, control of viral replication by innate immune responses in the brain is significant. Current research is examining the role of these innate immune responses on restricting viral RNA transcription and gene expression.
- Graduate Program in Biochemistry, Cell & Molecular Biology (1996 - )
- Admissions Committee
- Medical Scientist Training Program (MSTP) (2000 - )
- Advisory Board of the Medical Faculty (1999 - )
- Scientific Advisory Council (1999 - )
- Committee on Conflict of Interest (1996 - 2001)
- Women's Leadership Council (Permanent member)
Relevant Recent Articles
Clements, J.E., Babas, T., Mankowski, J., Suryanarayana, K., Piatak, M.J., Tarwater, P.M., Lifson, J., and Zink, M.C. The CNS as a Reservoir for SIV: Steady-state levels of SIV DNA in Brain from acute through asymptomatic infection. J. Infect. Dis. 186:905-13, 2002.
Shen, A., Zink, M.C., Mankowski, J.L., Chadwick, K., Margolick, J.B., Carruth, L.M., Li, M., Clements, J.E., and Siliciano, R.F. Abstract Resting CD4 (+) T Lymphocytes but Not Thymocytes Provide a Latent Viral Reservoir in a SIV – Macaca nemestrina Model of HIV Type 1 – Infected Patients on Highly Active Antiretroviral. J. Virol. 77:4938-49, 2003.
Babas T, Munoz D, Mankowski JL, Tarwater PM, Clements, JE, Zink M.C. Role of microglial cells in selective replication of simian immunodeficiency virus genotypes in the brain. J Virol. 77(1):208-16, 2003
Overholser, E.D., Coleman, G.D., Bennett, J.L., Casaday, R.J., Zink, M.C., Barber, S.A., and Clements, J.E. Expressions of SIV Nef in astrocytes during acute and terminal infection and requirement of Nef for optimal replication of neurovirulent SIV in vitro. J. Virol. 77:6855-6866, 2003.
Rue, S.M., Roos, J.M., Amzel, L.M., Clements, J.E., and Barber, S.A. Hydrogen bonding at a conserved threonine in lentivirus capsid is required for virus replication. J. Virology. 77(14):8009-18, 2003.
Weed, M.R., Hienz, R.D., Brady, J.V., Adams, R.J., Mankowski, J.L., Clements, J.E., Zink, M.C. Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection. J. Neurovirol. 9:452-464, 2003.
Barber, S.A., Herbst, D.S., Bullock, B.T., Gama, L., and Clements, J.E. Innate immune responses and control of acute SIV replication in the CNS. J. Neurovirol. 10 Suppl 1:15-20, 2004.
JL Mankowski, SE Queen, JE Clements, MC Zink. Cerebrospinal fluid markers that predict SIV CNS disease. Journal of Neuroimmunology. 157:66-70, 2004.
Bonavia A, Bullock BT, Gisselman KM, Margulies BJ, Clements JE. A single amino acid change and truncated TM are sufficient for simian immunodeficiency virus to enter cells using CCR5 in a CD4-independent pathway. Virology. 10;341(1):12-23, 2005.
Clements JE, Li M, Gama L, Bullock B, Carruth LM, Mankowski JL, Zink MC.
The central nervous system is a viral reservoir in simian immunodeficiency virus--infected macaques on combined antiretroviral therapy: a model for human immunodeficiency virus patients on highly active antiretroviral therapy. J Neurovirol. 11(2):180-9., 2005.
Rue SM, Roos JW, Clements JE, Barber SA. Conserved serines in simian immunodeficiency virus capsid are required for virus budding. Virology. 25;336(1):37-50, 2005.
Carruth LM, Zink MC, Tarwater PM, Miller MD, Li M, Queen LA, Mankowski JL, Shen A, Siliciano RF, Clements JE. SIV-specific T lymphocyte responses in PBMC and lymphoid tissues of SIV-infected pigtailed macaques during suppressive combination antiretroviral therapy.
J Med Primatol. ;34(3):109-21, 2005.
Overholser ED, Babas T, Zink MC, Barber SA, Clements JE. CD4-independent entry and replication of simian immunodeficiency virus in primary rhesus macaque astrocytes are regulated by the transmembrane protein. J Virol. ;79(8):4944-51, 2005.
Rue SM, Roos JW, Tarwater PM, Clements JE, Barber SA. Phosphorylation and proteolytic cleavage of gag proteins in budded simian immunodeficiency virus. J Virol. 79(4):2484-92, 2005.
Zink, M.C., Uhrlaub, J, DeWitt, J, Voelker, T, Bullock, B, Mankowski, J, Tarwater, P, Clements, J, Barber, S., Neuroprotective and Anti-Human Immunofeficiency Virus Activity of Minocycline. JAMA, 293(16):2003-2011, 2005.
Barber, S.A., Gama, L., Dudaronek, J.M., Voelker, T., Tarwater, P.M. and. Clements, J.E. Mechanism for Establishment of Transcriptional HIV Latency in the Brain using an SIV Macaque Model. J. Infectious Disease, In Press, 2006.