- Professor - Molecular & Comparative Pathobiology, Neurology, Pathology
- Joint appointment Molecular Biology & Genetics
- Vice Dean for Faculty
Graduate Program Affiliations:
- Biochemistry, Cell and Molecular Biology
- Cellular and Molecular Medicine
- Human Genetics
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. The studies that she did with the animal lentiviruses were used in the identification of HIV as a lentivirus in 1984. She joined the faculty of the Department of Neurology as an Assistant Professor in 1980, and the faculty of the Division of Comparative Medicine in 1988.
Dr. Clements has been the Vice Dean of Faculty of the School of Medicine since 2000. In this role she oversees all policies and programs related to faculty appointments and promotions as well as faculty development.
Dr. Clements was the first Director of the Department of Molecular and Comparative Pathobiology from 2002-2007. 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 HIV pathogenesis and AIDS Dementia and central nervous system (CNS) disease. Dr. Clements has directed the training of 28 Ph.D. and 3 M.S. students and 16 post-doctoral fellows.
Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, the interest is in understanding the pathogenesis of HIV and the development of HIV neurocognitive disease. In order to study HIV, the simian immunodeficiency virus (SIV) has been developed and is used to examine the molecular basis for the pathogenesis of HIV CNS disease as well as HIV latency and reactivation in the era of combined antiretroviral therapy (cART). The first SIV macaque model of virus suppression by cART was developed in the Retrovirus Laboratory in collaboration with the Slilciano HIV laboratory. 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 and latency of macrophages in the central nervous system and the lung are being pursued to characterize these cells as viral reservorirs during suppressive cART. 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.
Dr. Clements 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 focused on identifying the mechanism for viral latency in monocytes and macrophages, developing sensitive assays to quantitate latently infected monocytes, macrophages and resting CD4+ T cells in cART suppressed SIV-infected macaques and in identifying approaches to eradicating latently infected cells throughout the body in SIV models to provide a proof of concept for HIV eradication in humans.
- JHU Risk Assessment Standing Committee (2010-)
- Advisory Board of the Medical Faculty (1999- )
- Medical Scientist Training Program (MSTP) (2000- 2013)
- Committee on Conflict of Interest (1996-2001)
- Abreu CM, Price SL, Shirk EN, Cunha RD, Pianowski LF, Clements JE, Tanuri A, Gama L.Dual Role of Novel Ingenol Derivatives from Euphorbia tirucalli in HIV Replication: Inhibition of De Novo Infection and Activation of Viral LTR. PLoS One. 2014 May 14;9(5):e97257. doi: 10.1371/journal.pone.0097257. eCollection 2014.
- Akay C, Cooper M, Odeleye A, Jensen BK, White MG, Vassoler F, Gannon PJ, Mankowski J, Dorsey JL, Buch AM, Cross SA, Cook DR, Peña MM, Andersen ES, Christofidou-Solomidou M, Lindl KA, Zink MC, Clements J, Pierce RC, Kolson DL, Jordan-Sciutto KL. Antiretroviral drugs induce oxidative stress and neuronal damage in the central nervous system. J Neurovirol. 2014 Feb;20(1):39-53. doi: 10.1007/s13365-013-0227-1. Epub 2014 Jan 14
- Witwer, K.W., et al., Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients. Retrovirology, 2012. 9: p. 5.
- Zaritsky, L.A., L. Gama, and J.E. Clements, Canonical type I IFN signaling in simian immunodeficiency virus-infected macrophages is disrupted by astrocyte-secreted CCL2. J Immunol, 2012. 188(8): p. 3876-85.
- Cary, D.C., J.E. Clements, and A.J. Henderson, RON Receptor Tyrosine Kinase, a Negative Regulator of Inflammation, Is Decreased during Simian Immunodeficiency Virus-Associated Central Nervous System Disease. J Immunol, 2013. 191(8): p. 4280-4287.
- Sisk, J.M., et al., SIV replication is directly downregulated by four antiviral miRNAs. Retrovirology, 2013. 10(1): p. 95.
- Zaritsky, L.A., et al., Tissue-Specific Interferon Alpha Subtype Response to SIV Infection in Brain, Spleen, and Lung. J Interferon Cytokine Res, 2013. 33(1): p. 24-33.
- Ravimohan S, Gama L, Engle EL, Zink MC, Clements JE. Early emergence and selection of a SIV-LTR C/EBP site variant in SIV-infected macaques that increases virus infectivity. PLoS One. 2012;7(8):e42801. doi: 10.1371/journal.pone.0042801. Epub 2012 Aug 27. Erratum in: PLoS One. 2013;8(3).
- Deng K, Zink MC, Clements JE, Siliciano RF. A quantitative measurement of antiviral activity of anti-human immunodeficiency virus type 1 drugs against simian immunodeficiency virus infection: dose-response curve slope strongly influences class-specific inhibitory potential.J Virol. 2012 Oct; 86(20):11368-72. Epub 2012 Aug 8.
- Zaritsky LA, Gama L, Clements JE. Canonical type I IFN signaling in simian immunodeficiency virus-infected macrophages is disrupted by astrocyte-secreted CCL2. J Immunol. 2012 Apr 15;188(8):3876-85. doi: 10.4049/jimmunol.1103024. Epub 2012 Mar 9.