Joseph L. Mankowski, D.V.M., Ph.D., Diplomate ACVP

Professor of Molecular and Comparative Pathobiology
Professor of Pathology
Professor of Neurology

Background and Training

B.S. Cornell University, Neurobiology and Behavior
D.V.M. Cornell University
Ph.D. Johns Hopkins University
Diplomate, American College of Veterinary Pathologists

Research Focus

The Mankowski lab group studies the immunopathogenesis of HIV infection using the SIV/macaque model.

Pathogenesis of HIV-induced nervous system and cardiac disease processes

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 brain, the peripheral nervous system, and in the heart secondary to infection of macrophages. 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 activation. 

In addition, we are pursuing identification of surrogate biomarkers of HIV disease progression that can shed light on disease mechanisms and also be translated to the clinical setting.  For example, we have characterized CSF markers (IL-6 and 14-3-3 proteins) and hematologic markers (platelet decline) that precede and predict SIV and HIV CNS disease.  Close ties to clinical groups in JHU Neurology and Cardiology and proteomics-based collaborations with Dr.David Graham facilitate these efforts.

Host genetics and lentiviral-induced CNS disease

The role that host genetics play in HIV-associated cognitive disorders is poorly understood.  We have 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.

Students and Postdoctoral Fellows

Katie Kelly, DVM, PhD, Postdoctoral Fellow, ACVP/STP Coalition Fellow

Sarah Beck, DVM, PhD candidate, Cellular and Molecular Medicine Graduate Program

Kelly Pate, DVM, PhD, Postdoctoral Fellow

Lisa Mangus, DVM, PhD candidate, Celluar and Molecular Medicine Graduate Program

Research Staff

Jamie Dorsey

Suzanne Queen

Graduate Program Appointments

Pathobiology Graduate Program

Cellular and Molecular Medicine Graduate Program

Service

Dr. Mankowski provides diagnostic pathology support for the diverse animal species used in biomedical research at Johns Hopkins.

References

1.     Mankowski JL, Queen SE, Fernandez CS, Tarwater PM, Karper JM, Adams RJ, Kent SJ. Natural Host Genetic Resistance to Lentiviral CNS Disease: A Neuroprotective MHC class I allele in SIV-infected Macaques.  PLoS ONE, 3 Nov. 2008, 3(11): e3603.

2.     Ebenezer GJ, Laast VA, Dearman B, Hauer P, Tarwater PM, Adams RJ, Zink MC, McArthur JC, Mankowski JL. Altered cutaneous nerve regeneration in an SIV/macaque intracutaneous axotomy model. J. Comp Neurology, May 2009, 514(3): 272-83.

3.     Dinoso JB, Rabi A, Blankson JN, Gama L, Mankowski JL, Siliciano RF, Zink MC, Clements JE. An SIV-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J. Virology, 1 July 2009, 83(18): 9247-57.

4.     Gupta RG, Kelly KM, Helke KL, Queen SE, Karper JM, Dorsey JL, Brice AM, Adams RJ, Tarwater  PM, Kolson DL, MankowskiJL. HIV and SIV induce alterations in CNS CaMKII expression and activation: A potential mechanism for cognitive impairment. American Journal of Pathology, 9 Apr. 2010, 176(6) 2776-84.

5.     Lehman HC, Chen W, Borzan J, Mankowski JL, Hoke A. Mitochondrial dysfunction in distal axons contributes to HIV associated sensory neuropathy. Annals of Neurology, Jan 2011, 69(1) 100-10.

6.     Pate KA, Mankowski JL. HIV and SIV-associated thrombocytopenia: An expanding role for platelets in the pathogenesis of HIV.  In press, Drug Discovery Today: Disease Mechanisms, Summer 2011, 8(1-2), 25-32.

7.     Queen SE, Mears BM, Kelly KM, Dorsey JL, Liao Z, Dinoso JB, Gama L, Adams RJ, Zink MC, Clements JE, Kent SJ, Mankowski JL. Replication competent SIV Gag escape mutations archived in latent reservoirs during anti-retroviral treatment of SIV-infected macaques. J Virology, Sept 2011, 85(17), 9167-75.

8.     Laast VA, Shim B, Johanek LM, Dorsey JL, Hauer PE, Tarwater PM, Adams RJ, Pardo CA, McArthur JC, Ringkamp M, Mankowski JL. Macrophage-mediated dorsal root ganglion damage precedes altered nerve conduction in SIV-infected macaques. American Journal of Pathology, Nov 2011, 179(5), 2337-45

9.     Kelly KM, Tarwater PM, Karper JM, Bedja D, Queen SE, Tunin RS, Adams RJ, Kass DA, Mankowski JL. Diastolic Dysfunction is Associated with Myocardial Viral Load in SIV-infected Macaques. AIDS, April 2012 24; 26 (7):815-23.

10.  Ebenezer G, McArthur JC, Polydefkis M, Dorsey JL, O’Donnell R, Hauer P, Adams RJ, Mankowski JL. SIV-induced impairment of neurovascular repair: A potential role for VEGF.  ePub, J Neurovirology, May 2012.