Joseph L. Mankowski, DVM, PhD, DACVP
Cornell University, Ithaca NY
Johns Hopkins University, Baltimore MD
Dr. Joseph L. Mankowski is a Professor of Molecular and Comparative Pathobiology, Neurology, and Pathology at the Johns Hopkins University School of Medicine. His research team studies the immunopathogenesis of HIV infection using the SIV/macaque model. Dr. Mankowski received his undergraduate degree in Neurobiology and Behavior and his DVM from Cornell University. He completed both his PhD in Human Genetics and his residency training in Comparative Pathology at Johns Hopkins before joining the JHU faculty in 1996. He is a member of both Cellular and Molecular Medicine and Pathobiology graduate programs at JHU.
As a veterinary anatomic pathologist board-certified by the ACVP, Dr. Mankowski provides diagnostic and experimental pathology support for the diverse animal species and animal models used in biomedical research at Johns Hopkins. This clinical service is integrated with training DVM residents and postdoctoral fellows in diagnostic and experimental pathology and laboratory animal medicine.
Dr. Mankowski serves as the director of academic training for the department including leadership of the Veterinary Biomedical Research Scientist training program at Johns Hopkins University, now in its 41st year of NIH T32 support. He has been been recognized for outstanding mentorship at Johns Hopkins by the JHU Graduate Student Association and by faculty peers as a Master Mentor, directing trainee and faculty mentorship initiatives in the department. Dr. Mankowski has served as the interim director of the Department of Molecular and Comparative Pathobiology since 2014 and became director May 2018.
The Mankowski lab group studies the immunopathogenesis of HIV infection using the SIV/macaque model.
I developed an accelerated, consistent model of HIV CNS disease and HIV latency in SIV-inoculated macaques collaboratively with Janice Clements, Chris Zink, and Bob Siliciano. Johns Hopkins is a unique highly interactive environment to assemble complementary expertise in SIV models and HIV latency to address the critical challenge of HIV cure. In addition to studies of CNS disease and HIV latency, my research team has developed novel SIV models to study HIV-induced cardiac dysfunction and HIV peripheral neuropathy.
Pathogenesis of HIV-induced Organ-specific Damage
HIV is well known for its ability to induce loss of CD4+ T-cells leading to immune suppression manifest as AIDS. HIV infection also causes debilitating disease in the CNS, the peripheral nervous system, and in the heart secondary to infection of macrophages; damage to these organs persists despite the use of anti-retroviral therapy. Although virus-induced damage to these organs is common, the pathogenesis remains poorly defined. Using the SIV/macaque model of HIV, we use a multidisciplinary approach to dissect the mechanisms underlying these diseases, including the central role of macrophage infection and immune activation. We are now evaluating whether CCR5 inhibition reduces SIV latent reservoirs in macrophages in the CNS as well as other tissue sites.
Host genetics and lentiviral-induced CNS disease
The role that host genetics play in HIV-associated cognitive disorders is poorly understood. My lab team identified a novel association between expression of a MHC class I allele in pigtailed macaques and SIV-induced CNS disease that sets the stage for studies defining how MHC class I-mediated control of SIV replication in the brain influences SIV CNS disease outcomes. We are developing therapeutic vaccines against HIV that target the CNS.
Knight AC, Brill SA, Queen SE, Tarwater PM, Mankowski JL. Increased Microglial CSF1R Expression in the SIV/Macaque Model of HIV CNS Disease. J Neuropathol Exp Neurol. 2018 Jan 8.
Mangus LM, Beck SE, Queen SE, Brill SA, Shirk EN, Metcalf Pate KA, Muth DC, Adams RJ, Gama L, Clements JE, Mankowski JL. Lymphocyte-Dominant Encephalitis and Meningitis in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy. Am J Pathol. 2018 Jan;188(1):125-134.
Beck SE, Queen SE, Metcalf Pate KA, Mangus LM, Abreu CM, Gama L, Witwer KW, Adams RJ, Zink MC, Clements JE, Mankowski JL. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders. J Neurovirol. 2017 Oct 3.
Klein AH, Vyshnevska A, Hartke TV, De Col R, Mankowski JL, Turnquist BP, Bosmans F, Reeh PW, Schmelz M, Carr RW, Ringkamp M. Sodium channel NaV1.8 underlies TTX-resistant axonal action potential conduction in somatosensory C-fibers of distal cutaneous nerves. J Neurosci. 2017; 37:5204-5214
- Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM, Pate KA, Wietgrefe SW, O'Connor SL, Pianowski L, Haase AT, Van Lint C, Siliciano RF, Clements JE; LRA-SIV Study Group. Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS. 2017; 31:5-14