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

Associate Professor of Molecular and Comparative Pathobiology
Associate Professor of Pathology
Associate 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, PhD candidate, Pathobiology Graduate Program, ACVP/STP Coalition Fellow

Kelly Pate, PhD candidate, Cellular and Molecular Medicine Graduate Program

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

Wachtman LM, Tarwater PM, Queen SE, Adams RJ, Mankowski JL.  Platelet Decline: An Early Predictive Hematologic Marker of Simian Immunodeficiency Virus Central Nervous System Disease, J NeuroVirology, Feb 2006, p. 25-33.

Zink MC, Laast VA, Helke KL, Brice A, Barber SA, Clements JE, Mankowski JL.  From mice to macaques: Animal Models of HIV Neurologic Disease. Current HIV Research. July 2006, p. 293-305.

Laast V, Pardo C, Tarwater P, Queen SE, Reinhart TA, Ghosh M, Zink MC, Mankowski JL. Pathogenesis of SIV-induced Alterations in Macaque Trigeminal Ganglia. J Neuropath Exptl Neurology, Jan 2007, p 26-34.

Wachtman LM, Skolasky RL, Tarwater PM, Esposito D, Schifitto G, Marder K, McDermott M, Cohen B, Nath A, Mankowski JL, McArthur JC. Platelet Decline: An avenue for investigation into the pathogenesis of Human Immunodeficiency Virus (HIV)-Associated Dementia. In press, Arch Neurology, 2007.

Clements JE, Mankowski JL, Gama,L, Zink MC. The accelerated simian immunodeficiency virus macaque model of human immunodeficiency virus-associated neurological disease: From mechanism to treatment. J. Neurovirology, Aug 2008, p. 309-317.

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, Nov 3, 2008.

Ebenezer G, 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, p. 272-283.

Dinoso JB, Rabi A, Blankson JN, Gama L, Mankowski JL, Siliciano RF, Zink MC, Clements JE. An SIV-infected model to study viral reservoirs that persist during highly active antiretroviral therapy. J Virology, July 2009.

Witwer KW, Gama L, Li M, Bartizal C, Queen SE, Varrone J, Brice A, Graham DR, Mankowski JL, Zink MC, Clements JE. Failure of Early Synchronous Host Control of SIV Replication and Inflammation leads to CNS Disease.  PLoS ONE, Dec 17, 2009.

Jansen T, Tyler B, Mankowski JL, Recinos VR, Pradilla G, Legnani F, Laterra J, Olivi A.  FasL gene knock-down therapy enhances the antiglioma immune responses.  In press, Neuro-Oncology, 2010.

Zink MC, Brice AK, Kelly KM, Queen SE, Gama L, Li M, Adams RJ, Bartizal C, Varrone J, Rabi SA, Graham DR, Tarwater PM, Mankowski JL, Clements JE. SIV-infected macaques treated with HAART have reduced CNS virus replication and inflammation but persistence of viral DNA. J Infectious Disease, 2010.

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, 2010.