Professor, Comparative Medicine, Neurology, Pathology
and joint appointment Molecular Biology & Genetics
Graduate Program Affiliations:
Biochemistry, Cell and Molecular Biology
Cellular and Molecular Medicine
Background & Training:
Dr. Clements received a Ph.D. 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 expertise in neurovirology and viral pathogenesis comes from her studies of the animal lentiviruses and their role in chronic neurological diseases. Using these viruses, she developed the first molecular and biochemical tools to study lentivirus molecular biology and was the first to characterize the unusual genome of the lentiviruses. She joined the faculty of the Department of Neurology as an Assistant Professor, and then the faculty of the Division of Comparative Medicine in 1988.
Dr. Clements recently stepped down from her position as the first Director of the Department of Molecular and Comparative Pathobiology; the department had divisional status until 2002. Molecular and Comparative Pathobiology is a department 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 the faculty, students and postdoctoral fellows 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 18 Ph.D. and 2 M.S. students and 14 post-doctoral fellows.
Dr. Clements has served as Vice Dean for Faculty of the School of Medicine since 2000.
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.
Her group was the first to identify the role of CD4-independent virus entry in the pathogenesis of neurological disease. They 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. Furthermore, 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. Their 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, they 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.
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:
Edinger AL, Mankowski JL, Doranz BJ, Margulies BJ, Lee B, Rucker J, Sharron M, Hoffman TL, Berson JF, Hirsch VM, Clements JE, Doms RW. CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc Natl Acad Sci USA, 94(26):14742-14747, 1997
Zink MC, Coleman GD, Mankowski JL, Adams RJ, Tarwater PM, Fox K, Clements JE. Increased Macrophage chemoattractant protein-1 in cerebrospinal fluid precedes and predicts simian immunodeficiency virus encephalitis. J Infect Dis 184:1015-1021, 2001
Clements JE, Babas T, Mankowski JL, Suryanarayana K, Piatak M Jr, Tarwater PM, Lifson JD, Zink MC. The central nervous system as a reservoir for simian immunodeficiency virus: steady-state levels of DNA in brain from acute through asymptomatic infection. J Infect Dis 186(7):905-13, 2002
Shen A, Zink MZ, Mankowski JL, Chadwick K, Margolick JB, Carruth LM, Li M, Clements JE, Siliciano RF. Resting CD4+ T lymphocytes but not thymocytes provide a latent viral reservoir in a simian immunodeficiency virus-macaca nemestrinamodel of human immunodeficiency virus Type 1-infected patients on highly active antiretroviral therapy. J Virol 77(8):4938-4949, 2003
Bonavia, A., B.T. Bullock, K.M. Gisselman, B.J. Margulies, CLEMENTS, J.E.: 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, 341(1):12-23, 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, 193(7):963-70, 2006.
Barber, S.A.,Gama, L. Li, M., Voelker, T., Anderson, J.E., Zink, M.C. and CLEMENTS,
J.E. Longitudinal Analysis of SIV Replication in the Lung: Compartmentalized Regulation of SIV. J. Infectious Disease, 194(7):931-8, 2006.