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Velpandi Ayyavoo, PhD

Professor and Assistant Chair, Infectious Diseases and Microbiology

Associate Dean for Faculty Affairs, Office of the Dean

Graduate Programs Director, Infectious Diseases and Microbiology

Contact

A435 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261
R-znvy: irycnaqv@cvgg.rqh
Primary Phone: 967-179-8525


Personal Statement

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.

Biomarker drug target discovery and validation.
Biomarkers represent the measurable biological molecules or factors which can be used as indicators of normal or disease state.  Recent advances in molecular biology techniques have exploded the range of potential biomarkers including genomic transcriptome and proteomic approaches.  Various approaches are being utilized to identify unconventional disease specific biomarker as early detection tools for diagnosis of other human diseases such as cancer neurological disorders, cardiac diseases.  miRNAs, a family of small, non-coding RNAs, of 19-25 nucleotides long that regulate gene expression post-transcriptionally, are explored as early biomarkers and/or diagnostic tool for many diseases including cancer, Alzheimer's and have gained strong interest in recent years.  Many studies have demonstrated that dysregulation of these miRNAs is associated with various diseases suggesting that there is potential for use of miRNAs in diagnosis and treatment.  More recently, serum miRNAs as well as blood cell drived miRNAs are explored as noninvasive diagnostic biomarker tools for Parkinson disease, glioblastoma and other diseases.  At present there are no early biomarkers available to detect HAND or any other HIV-1 associated comorbidities.  Therefore, an early diagnosis and better treatment options to treat and/or manage HAND will be beneficial to the patients.  Our goal here is to develop a sensitive miRNA biomarker based noninvasive molecular diagnostic tool to detect the development of HAND in HIV-1 positive subjects.  Additionally these miRNAs also have the ability to serve us new drugs that could potentially regulate gene expression associated with disease progression. 


Education

1991 | Madurai Kamaraj University, India | Doctor of Philosophy
1991-1993 | The Wistar Institute | Postdoctoral Fellow
1994-1998 | The University of Pennsylvania | Research Associate


Teaching

IDM 2001 - Molecular Biology of Microbiol Pathogens
IDM 2023 - Laboratory Methods
IDM 2025 - Seminar Series & Journal Club
IDM 2010 - Pathogen Biology
IDM 2014 - Functional Genomics


Rotation Projects - Fall 2014

1. Understanding the role of host and viral factors in HIV-1 Neuropathogenesis
2. Mechanisms involved in HIV-1 latency: HIV-1 Cure strategies
3. Biomarker discovery and validation


Selected Publications

Majumder B, Venkatachari NJ, Ayyavoo V.  (2008)  Human Immunodeficiency Virus type 1 Viral Protein R (HIV-1Vpr) impairs NK cell activation through dysregulation of infected target cells. J Virol. 82:7189-200.

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 vivo. Virology 376:140-53.

Majumder B, Venkatachari NJ, Srinivasan A, Ayyavoo V.  (2009)  HIV-1 mediated immune pathogenesis: spotlight on the role of viral protein R (Vpr). Curr HIV Res. 7:169-77.

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: 7470.

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.

Guha D, Nagilla P, Redinger C, Srinivasan A, Schatten G Ayyavoo V. (2012)  Neuronal apoptosis by HIV-1 Vpr: Contribution of pro-inflammatory molecular networks from infected target cells. J Neuroinflammation 9:138-152.

Duskova K, Nagilla P, Le H, Iyer P, Thalamuthu A, Martinson J, Bar-Joseph Z, Buchanan W, Rinaldo C, Ayyavoo V.  (2013)  MicroRNA regulation and its effects on cellular transcriptome in Human Immunodeficiency Virus-1 (type-1) infected individuals with distinct viral load and CD4 cells. BMC Genomics 13:250.

Zych C, Domling A, Ayyavoo V.  (2013)  Development of a robust cell- based high-throughput screening assay to identify targets of HIV-1 Vpr dimerization. J. Drug Design Develop. Therapy 7:403-412.

Hadi K, Walker LA, Tarwater P, Srinivasan A, Ayyavoo V.  (2014)  Human Immunodeficiency Virus- type 1 (HIV-1) Vpr polymorphisms associated with progressors and non-progressor individuals alter Vpr associated functions. J. Gen. Virol. 95:700-711.

Guha D, Klamar CR, Reinhart T, Ayyavoo V.  (2015)  Transcriptional regulation of CXCL5 in HIV-1-infected macrophages and its functional consequences on CNS Pathology.  J. Interferon Cytokine Res.  35:373-384.

Venkatachari NJ, Zerbato JM, Jain S, Mancini AE, Chattopadhyay A, Suis-Cremer N, Bar-Joseph Z, Ayyavoo V.  (2015)  Temporal transcriptional response to latency reversing agents identifies specific factors regulating HIV-1 viral transcriptional switch.  Retrovirol.  12:85.

Jain S, Arrais J, Venkatachari NJ, Ayyavoo V, Bar-Joseph Z.  (2016)  Reconstructing the temporal progression of HIV-1 immune response pathways.  Bioinformatics  32:i253-i261.

Guha D, Mancini A, Sparks J, Ayyavoo V.  (2016)  HIV-1 infection dysregulates cell cycle regulatory protein p21 in CD4+ T cells through miR-20a and miR-106b regulation.  J Cell Biochem  11:1902-1912.

Venkatachari NJ, Jain S, Walker L, Bivalkar-Mehla S, Chattopadhyay A Bar-Joseph Z, Rinaldo C Ragin A, Seaberg E, Levine A, Becker J, Martin E, Sacktor N, Ayyavoo V.  (2016) Transcriptome analyses identify key cellular factors associated with HIV-1 associated neuropathogenesis in infected men.  AIDS


For a full list publications, click this link:  https://www.ncbi.nlm.nih.gov/pubmed/?term=ayyavoo+v

Velpandi  Ayyavoo
© 2017 by University of Pittsburgh Graduate School of Public Health

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