Associate Professor and Director of IDM Graduate Programs and Director of PhD Program


Email: velpandi@pitt.edu
Phone: 412-624-3070
Fax: 412-624-5612

Address:
425 Parran Hall
130 DeSoto Street
Pittsburgh, PA 15261


Education

PhD; Madurai Kamaraj University, India, 1991
Postdoctoral Fellow; The Wistar Institute, 1991-1993
Postdoctoral Fellow; The University of Pennsylvania, 1994-1998

Research Interests

HIV-1 induced neuropathogenesis:  Role of viral and cellular factors
HIV-associated dementia (HAD) is commonly observed in AIDS patients worldwide. The hallmark of HAD is the loss of neurons, astrocytes activation and neuronal cell dysfunction. During early infection, HIV-1 enters the Central Nervous System (CNS) and resides in macrophages/microglia. Though HIV replicates in macrophages/microglia and in astrocytes at a low level in CNS compartment, neurons are the mostly affected cell types in vivo. These observations suggest that viral proteins and cellular factors associated with HIV-1 infection are the leading cause of neuronal degeneration and neuropathogenesis. Our laboratory focuses on understanding how HIV-1 Vpr induces neuronal apoptosis and destruction. In the infected individuals, Vpr is present in cell-associated, virion-associated and cell and virion-free forms. We hypothesize that HIV-1 Vpr regulates neurons either by directly affecting them and/or indirectly through the infected target cells such as macrophages/microglia and astrocytes within the CNS compartment.   We propose to test our hypothesis by the following aims: (i) determine the mechanism(s) involved in Vpr mediated neuronal loss and dysfunction directly; (ii) identify the cellular cofactors and neuroinflammatory molecules differentially regulated by Vpr in target cells; and (iii) identify the structure-function relation of Vpr to neuropathogenesis using naturally occurring Vpr variants from CNS compartment. Results from this study will help to identify novel targets and to design new therapeutics against HIV-1 in the central nervous system.

Integrated analysis of microRNA and mRNA expression profile in HIV-1 patients.
MicroRNAs are of significant interest to HIV-1 infection because they have a unique expression profile in cells of the innate and adaptive immune systems as well as in cancer cells. We hypothesize that non-coding microRNAs in target cells of HIV-1 infected individuals play a major role in altering viral and host gene expression, target cell susceptibility, immune responses and disease outcome. We are interested in evaluating the expression profile of host cellular microRNA, mRNA and further correlate the interplay between these factors with HIV-1 disease progression. Results from this study will have significant impact on biomarker discovery and potential antiviral targets as identified in cancer patients and other diseases.

Antiviral drug development and high content screening
Dramatic improvements in treating HIV-1 infected individuals have been attained with Highly Active Anti-Retroviral Therapy. Most anti-retroviral treatment regimes, however, fail to provide complete and long-term suppression of viral replication, and therefore do little in the control of disease progression. This has prompted us to consider developing small molecule inhibitors targeting conserved functions of other HIV-1 viral proteins as well as viral-host interactions. Several viral proteins (Gag, Nef, Vpr and protease) form dimers and/or oligomers and this feature is important for their functions in virus biology. Thus targeting HIV protein oligomerization feature will provide additional potent antivirals that are underexplored. We have selected the BiFC dimerization assay as the assay of choice as it involves two molecules of Vpr and the interaction can also be measured precisely. BiFC based high content screening assay is a powerful, fast and inexpensive tool for screening compounds using physiologically relevant cell culture systems. Using this novel method, we propose to identify several drug targets for HIV-1. Successful development of HCS using the BiFC will pave the way to target other HIV viral proteins as well as virus-host interaction partners, thus have an overall impact in targeting protein-protein interactions.

Rotation Projects 2012

Role of HIV-1 viral proteins in neuropathogenesis and dementia

Biomarkers for early detection of HIV-1 and HIV-1 associated diseases

MicroRNA, mRNA profiling in HIV-1pathogenesis

Recent Publications

Majumder B, Janket ML, Schafer EA, Kan-Mitchell J, Huang X, Rinaldo CR, and Ayyavoo V. (2005). Human immunodeficiency virus type 1 (HIV-1) Vpr impairs dendritic cell maturation and T cell activation: implications in viral immune escape. J Virol. 79:7990-8003.

Miles MC, Janket ML, Wheeler EA, Chattopadhyay A , Majumder B, Schafer EA, and Ayyavoo V. (2005) Molecular and functional characterization of a novel splice variant of ANKHD1 that lacks the KH domain and its role in cell survival and apoptosis. FEBS J, 272: 4091-4102.

Wheeler ED, Achim, CL, and Ayyavoo, V. (2006). Immunodetection of Human Immunodeficiency Virus type 1 (HIV-1) Vpr in brain tissue of HIV-1 encephalitic patients. J. NeuroVirol. J Neurovirol. 12:200-10.

Schafer EA, Venkatachari NJ, and Ayyavoo V. (2006). Antiviral Effects of Mifepristone on Human Immunodeficiency Virus Type-1 (HIV-1): Targeting Vpr and its cellular partner, Glucocorticoid receptor (GR). Antiviral Res. 72:224-32.

Cui J, Tungaturthi PK, Ayyavoo V, Ghafouri M, Ariga H, Khalili K, Srinivasan A, Amini S, Sawaya BE. (2006). The role of Vpr in the regulation of HIV-1 gene expression. Cell Cycle. 5: 2626-2638.

Venkatachari NJ, Majumder B, Ayyavoo V. (2007). Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: direct effect of Vpr on T cell activation and immune function. Virology 358:347-56.

Janket ML, DeRicco JS, Borowski L, Ayyavoo V. (2007). Human immunodeficiency virus (HIV-1) Vpr induced downregulation of NHE1 induces alteration in intracellular pH and loss of ERM complex in target cells. Virus Res. 126:76-85.

Majumder B, Venkatachari NJ, Schafer EA, Janket ML, Ayyavoo V. (2007). Dendritic cells infected with vpr-positive human immunodeficiency virus type 1 induce CD8+ T-cell apoptosis via upregulation of tumor necrosis factor alpha. J Virol. 81:7388-99.

Venkatachari NJ, Buchanan WG, Ayyavoo V. (2008). Human immunodeficiency virus (HIV-1) infection selectively downregulates PD-1 expression in infected cells and protects the cells from early apoptosis in vitro and in viv. Virology 376:140-153

Majumder B, Venkatachari NJ, O'Leary S, Ayyavoo V. (2008). Vpr positive Human Immunodeficiency Virus (HIV-1) infection impairs NK cell function indirectly through cytokine dysregulartion of infected target cells. J Virol. 82:7189-7200

Venkatachari NJ, Alber S, Watkins SC, Ayyavoo V. (2009). HIV-1 infection of DC: evidence for the acquisition of virus particles from infected T cells by antigen uptake mechanism.  PLoS One 4:e7470.

Venkatachari NJ, Walker LA, Tastan O, Le T, Dempsey TM, Li Y, Yanamala N, Srinivasan A, Klein-Seetharaman J, Montelaro RC, Ayyavoo V.  (2010). Human immunodeficiency virus type 1 Vpr: oligomerization is an essential feature for its incorporation into virus particles. Virology J. 7:119.

Mehla R, Ayyavoo V. (2012). Gene array studies in HIV-1 infection. Curr HIV/AIDS Rep. 9(1):34-43.

Guha D, Nagilla P, Redinger C, Srinivasan A, Schatten GP, Ayyavoo V  (2012). Neuronal apoptosis by HIV-1 Vpr: contribution of proinflammatory molecular networks from infected target cells. Journal of Neuroinflammation 2012, 9:138.


Dr. Ayyavoo's Lab


Personnel

Dr. Debjani Guha, PhD; deg59@pitt.edu
416 Parran Hall; 624-3062

Rajeeve Mehla, PhD; ram163@pitt.edu
416 Parran Hall; 624-3062

Shalmali Bivalkar, PhD; ssb29@pitt.edu
416 Parran Hall; 624-3062

Jessica Sparks; jks44@pitt.edu
416 Parran Hall; 624-3062

Jeffery Johns
416 Parran Hall; 624-3062

Alumni

Vanitharani Ramachandran, PhD (Post doctoral fellow). Current position: Assistant Specialist, University of California Riverside, CA.

Benjamin Gray, DMD, MPH (Dental Fellow; MPH student). Current Position: Dental officer, USS Frank Cable.

Ramesh K. Ramalingam, PhD (postdoctoral fellow). Current position: Research Fellow, University of Vanderbilt, Nashville, TN.

Dineshkumar Thotala, PhD (postdoctoral fellow). Current Position: Research Instructor, Washington University, St. Louis, MO.

Melissa C. Miles (MS, 2004). Current position: Instructor, United States Army, West Point, NY.

Michelle L. Janket (PhD, 2005). Current position: Resident, Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, NC.

Elizabeth A. Schafer (MS, 2005). Current position: Microbiologist, Department of Agricultural Research Services, USDA, Plum Island, NY.

Elizabeth Wheeler (MS, 2005). Current position: Unknown.

Danielle McKeithen (MPH, 2006). Current position: Research Specialist, Clark Atlanta University, Atlanta, GA.

Krisztina Baglyas (MS, 2008). Current position: Senior Microbiologist, Battelle Biomedical Research, NCI/NIH, Frederick, MD.

Shaylee O'Leary (MS, 2008). Current position: Product Development Associate, Cook MyoSite Incorporated, Pittsburgh, PA

Biswanath Majumder, PhD (Research Associate). Current position: Senior Scientist, Mitra Life Sciences India Pvt Ltd, India.

Venkatachari, Jayanth (PhD, 2009). Current position: Post Doctoral Fellow, NCI/NIH, Frederick, MD.

Dr. Ankit Gupta (Visiting Post-Doctoral Fellow). Current position: Resident, Internal Medicine, Chicago, IL

Timothy Dempsey (Undergraduate Researcher). Current position: Medical Student, Robert Wood Johnson Medical Center, Piscataway, NJ.

Courtney Zych (MS 2011). Current position: R&D Specialist, PPD, Richmond, Virginia.

Karolina Duskova (MS 2012). Current position: Clinical Research Specialist, Novum Parmaceutical Research Services, Pittsburgh, PA.

Kevin Hadi (MS 2012). Current position: Research Specialist, Department of Surgery, University of Pittsburgh, Pittsburgh, PA.

Dr. Ayyavoo's Lab