Medical Education Discipline

Dr. Virginie Bottero received her PhD in Molecular and Cellular Aspects of Biology from the University of Nice-Sophia Antipolis, France in 2002. She worked as a postdoctoral fellow at the Salk Institute for Biological Studies, La Jolla, CA from 2002 to 2006. She joined ����Ⱥ�� of Medicine and Science in July 2006.

RESEARCH

Dr. Bottero’s research interest is in the area of gene regulation. She has investigated how certain transcription factors are activated and how they influence the expression of genes involved in the development of different diseases such as cancers, viral infection and neurodegeneration.

Understanding the differentially expressed genes in a disease could allow for the development of biomarkers. She has applied bioinformatic and network analyses to uncover Parkinson’s disease biomarkers. The potential biomarkers were tested by real-time PCR from RNA extracted from the blood of healthy individual as well as Parkinson’s and Progressive Supranuclear Palsy patients. 

More recently, using the same methodologies, she is attempting to differentiate different types of dementias and to understand the mechanisms underlying their pathogenesis. Using publicly available transcriptomic data, she elucidated shared and specific transcriptional signatures in each dementia type and determined the pathways involved. Because type II diabetes is one of the largest risk factors for dementia, she is also determining if patients with type II diabetes share dysregulated pathways with dementia patients and whether individuals on a Mediterranean diet share pathways similar to healthy controls, suggesting this lifestyle choice may be neuroprotective.

PEER-REVIEWED PUBLICATIONs

Bottero V, Santiago JA, Potashkin JA. PTPRC Expression in Blood is Downregulated in Parkinson's and Progressive Supranuclear Palsy Disorders. J Parkinsons Dis. 2018;8(4):529-537. doi: 10.3233/JPD-181391. PMID: 30248063

Santiago JA, Bottero V, Potashkin JA. Evaluation of RNA Blood Biomarkers in the Parkinson's Disease Biomarkers Program. Front Aging Neurosci. 2018 May 29;10:157. doi: 10.3389/fnagi.2018.00157. eCollection 2018. PMID: 29896099

Santiago JA, Bottero V, Potashkin JA. Biological and Clinical Implications of Comorbidities in Parkinson’s Disease. Front Aging Neurosci. 2017 Dec 4;9:394. PMID: 29255414

Santiago JA, Bottero V, Potashkin JA. Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology. Front Aging Neurosci. 2017 May 29;9:166. PMID: 28611656

Mohanan Valiya Veettil, Binod Kumar, Mairaj Ansari, Dipanjan Dutta, Jawed Iqbal, Olsi Gjyshi, Virginie Bottero, and Bala Chandran. ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells. J Virol. 2016 Mar 28;90(8):3860-72. PMID: 26819309

Stephanie Flaherty, Olsi Gjyshi, Mohanan Valiya Veettil, Karen E. Johnson, Bala Chandran and Virginie Bottero*. Kaposi’s Sarcoma-Associated Herpesvirus Induces Nrf2 Activation in Latently-Infected Endothelial Cells through SQSTM1 Phosphorylation and Interaction with Polyubiquitinated Keap1. J Virol. 2015 Feb 15;89(4):2268-86. PMID: 25505069. *corresponding author

Karen E. Johnson, Virginie Bottero, Vivek Vikram Singh, Stephanie Flaherty, Bala Chandran Host Nuclear Innate Immune Sensor, IFI16, Restricts HSV-1 Replication by Regulating Gene Expression of all Temporal Classes of HSV-1 genes and Inducing Chromatin Remodeling. PLoS Pathog. 2014 Nov 6;10(11):e1004503. PMID: 25375629.

Olsi Gjyshi, Virginie Bottero, Mohanan Valliya Veettil, Sujoy Dutta, Vivek Vikram Singh, Leela Chikoti and Bala Chandran Kaposi's Sarcoma-Associated Herpesvirus Induces Nrf2 During De Novo Infection of Endothelial Cells to Create a Microenvironment Conducive for Infection and Establishment of Latency. PLoS Pathog. 2014 Oct 23;10(10):e1004460. PMID: 25340789.

Mohanan Valliya Veettil, Dipanjan Dutta, Virginie Bottero, Chirosree Bandyopadhyay, Olsi Gjyshi, Neelam Sharma-walia, Sujoy Dutta and Bala Chandran. Glutamate secretion and metabotropic glutamate receptor 1 expression during Kaposi’s sarcoma-associated herpesvirus infection promotes cell proliferation. PLoS Pathog. 2014 Oct 9;10(10):e1004389. PMID: 25299066.

Sujoy Dutta, Chirosree Bandyopadhyay, Virginie Bottero, Mohanan V. Veettil, Lydia Wilson, Michael R. Pins, Karen E. Johnson, Case Warshall and Bala Chandran. Angiogenin interacts with the plasminogen activation system at the cell surface of breast cancer cells to regulate plasmin formation and cell migration. Molecular Oncology Journal. 2014 May;8(3):483-507. PMID: 24457100.

Virginie Bottero*, Sathish Sadagopan, Karen E. Johnson, Sujoy Dutta, Mohanan Valiya Veettil and Bala Chandran. Kaposi’s Sarcoma-Associated Herpesvirus Positive Primary Effusion Lymphoma Tumor Formation in NOD/SCID Mice Is Inhibited by Neomycin and Neamine Blocking Angiogenin’s Nuclear Translocation. J Virol. 2013 Nov;87(21):11806-11820. PMID: 23986578. *corresponding author

Singh VV#, Kerur N#, Bottero V#, Dutta S, Chakraborty S, Ansari MA, Paudel N, Chikoti L, Chandran B. Kaposi's Sarcoma-Associated Herpesvirus Latency in Endothelial and B cells Activates Interferon Gamma-Inducible Protein 16 (IFI16) Mediated Inflammasomes. J Virol. 2013 Apr;87(8):4417-31. PMID: 23388709. #Authors contributed equally.

Bottero V*, Chakraborty S, Chandran B. Reactive Oxygen Species Are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during Primary Infection of Endothelial Cells To Promote Virus Entry. J Virol. 2013 Feb;87(3):1733-49. PMID: 23175375. *corresponding author

Chakraborty S, ValiyaVeettil M, Bottero V, Chandran B. Kaposi’s sarcoma-associated herpesvirus interacts with EphrinA2 receptor to amplify signaling essential for productive infection. Proc. Natl. Acad. Sci. USA. 2012 May 8;109(19):E1163-72. PMID: 22509030.

Sharma-Walia, N, Patel. K,  Chandran K, Bottero V, Kerur N, Paul AG, and Chandran B. Role of v FLIP in COX-2 induction and KSHV latency. Oncogenesis. (2012) 1, e5; doi:10.1038/oncsis.2012.5. PMID: 23552603.

Sadagopan S, Veettil MV, Chakraborty S, Sharma-Walia N, Paudel N, Bottero V, Chandran B. Angiogenin functionally interacts with p53 and regulates p53-mediated apoptosis and cell survival. Oncogene. 2012 Jan 23. doi:10.1038/onc.2011.648. PMID: 22266868.

Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B. IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus. Cell Host Microbe. 2011 May 19;9(5):363-75. PMID: 21575908.

Sadagopan S, Veettil MV, Paudel N, Bottero V, Chandran B. Kaposi`s sarcoma-associated herpesvirus (KSHV) induced angiogenin play roles in latency via PLCg pathway and blocking angiogenin inhibits lantent gene expression and induces lytic cycle. J Virol. 2011 Mar;85(6):2666-85. PMID: 21209106.

Bottero V*, Patel K, Sharma-Walia N, Sadagopan S, Chandran B. TGFb Activating Kinase 1 (Tak1) is involved in NF-kB activation and tumorigenesis induced by Kaposi Sarcoma-associated herpes virus (KSHV) G protein-coupled receptor (vGPCR). J Virol. 2011 Mar;85(5):1980-93. PMID: 21159881. *corresponding author

Kerur N, Veettil MV, Sharma-Walia N, Sadagopan S, Bottero V, Paul AG, Chandran B. Characterization of entry and infection of monocytic THP-1 cells by Kaposi's sarcoma associated herpesvirus (KSHV): role of heparan sulfate, DC-SIGN, integrins and signaling.  Virology. 2010 Oct 10;406(1):103-16. PMID: 20674951.

Sharma-Walia N, Bottero V#, Paul AG#, Sadagopan S, Veettil MV, Kerur N, Chandran B. Kaposi’s sarcoma associated herpes virus (KSHV) induced cyclooxygenase (COX)-2: A key factor in latency, inflammation, angiogenesis, cell survival and invasion. PLoS Pathogens.  2010 Feb 12;6(2):e1000777. PMID: 20169190. #Both authors contributed equally.

Bottero V, Sharma-Walia N, Kerur N, Paul AG, Sadagopan S, Cannon M, Chandran B. Kaposi Sarcoma-associated herpes virus (KSHV) G protein-coupled receptor (vGPCR) activates the ORF50 lytic switch promoter: A potential positive feedback loop for sustained ORF50 gene expression. Virology. 2009;392(1):34-51. PMID: 19640558.

Xia Y, Padre RC, De Mendoza TH, Bottero V, Tergaonkar VB, Verma IM. Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP. Proc Natl Acad Sci USA. 2009;106(8):2629-34. PMID: 19196987.

Sadagopan S, Sharma-Walia N, Veettil MV, Bottero V, Levine R, Vart RJ, Chandran B. Kaposi's Sarcoma Associated Herpes Virus (KSHV/HHV-8) Upregulates Angiogenin During Infection of Human Dermal Microvascular Endothelial Cells Which Induces 45SrRNA Synthesis, Anti-apoptosis, Cell Proliferation, Migration and Angiogenesis. J Virol. 2009;83(7):3342-64. PMID: 19158252.

Sivakumar R, Sharma-Walia N, Raghu H, Veettil MV, Sadagopan S, Bottero V, Varga L, Levine R, Chandran B. Kaposi's sarcoma-associated herpesvirus induces sustained levels of vascular endothelial growth factors A and C early during in vitro infection of human microvascular dermal endothelial cells: biological implications. J Virol. 2008;82(4):1759-76. PMID: 18057235.

Frelin C, Imbert V, Bottero V, Gonthier N, Samraj AK, Schulze-Osthoff K, Auberger P, Courtois G, Peyron JF. Inhibition of the NF-kB survival pathway via caspase-dependent cleavage of the IKK complex scaffold protein and NF-kB essential modulator NEMO. Cell Death Differ. 2008;15(1):152-60. PMID: 17932497.

Raghu H, Sharma-Walia N, Veettil MV, Sadagopan S, Caballero A, Sivakumar R, Varga L, Bottero V, Chandran B. Lipid Rafts of Primary Endothelial Cells Are Essential for Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8) Induced PI3-K and RhoA-GTPases Critical for Microtubule Dynamics and Nuclear Delivery of Viral DNA but Dispensable for Binding and Entry. J Virol. 2007;81(15):7941-59. PMID: 17507466.

Sadagopan S, Sharma-Walia N, Veettil MV, Raghu H, Sivakumar R, Bottero V, Chandran B. Kaposi's sarcoma-associated herpesvirus induces sustained NF-kappaB activation during de novo infection of primary human dermal microvascular endothelial cells that is essential for viral gene expression. J Virol. 2007;81(8):3949-68. PMID: 17287275.

Ghosh S, Tergaonkar V, Rothlin CV, Correa RG, Bottero V, Bist P, Verma IM, Hunter T. Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kB activation and cell survival. Cancer Cell. 2006;10(3):215-26. PMID: 16959613.

Muotri AR, Bottero V, Tergaonkar V and Correa RC. UV-Mediated NF-κB Activation is Abolished in Deficient XPC/D Primary Fibroblasts. Cell cycle, 2006;5(10):1085-9. PMID: 16721051.

Woods NB, Bottero V, Verma IM. Therapeutic gene for XSCID gene therapy trial results in T-cell lymphoma in mice, Nature. 2006;440(7088):1123. PMID: 16641981.

Magne N, Toillon RA, Bottero V, Didelot C, Houtte PV, Gerard JP, Peyron JF. NF-kB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett. 2006;231(2):158-68. PMID: 16399220.

Bottero V, Withoff S, Verma IM. NF-kB and the regulation of hematopoiesis. Review article. Cell Death Differ. 2006;13(5):785-97. PMID: 16528384.

Li Q, Lu Q, Bottero V, Estepa G, Morrison L, Mercurio F and Verma IM. Enhanced NF-B activation and cellular function in macrophages lacking IB kinase 1 (IKK1).  Proc Natl Acad Sci USA. 2005;102(35):12425-30. PMID: 16116086.

Ducut JL, Bottero V, Young DB, Shevchenko A, Mercurio F, Verma IM. ELKS, a regulatory subunit of IkB kinase complex required for NF-kB activation. Science. 2004;304(5679):1963-7. PMID: 15218148.

Bottero V, Imbert V, Frelin C, Formento JL, Peyron JF. Monitoring NF-kB Transactivation Potential Via Real-Time PCR Quantification of IkB-a Gene Expression. Mol Diagn. 2003;7(3):187-94. PMID: 15068390.

Tergaonkar V, Bottero V, Ikawa M, Li Q, Verma IM. IkB kinase-independent IkBa degradation pathway: functional NF-kB activity and implications for cancer therapy. Mol Cell Biol. 2003;23(22):8070-83. PMID: 14585967.

Busuttil V, Bottero V, Frelin C, Imbert V, Ricci JE, Auberger P, Peyron JF. The blockade NF-kB activation in Jurkat leukemic T cells converts the survival agent and tumor promoter PMA into an apoptotic effector. Oncogene, 2002, vol. 21, no. 20 pp. 3213-3224. PMID: 12082637.

Cursio R, Mari B, Louis K, Rostagno P, Saint-Paul MC, Giudicelli J, Bottero V, Anglard P, Yiotakis A, Dive V, Gugenheim J and Auberger P. Rat Liver Injury Following Normothermic Ischemia is prevented by a Phosphinic Matrix Metalloproteinase Inhibitor. FASEB J. 2002;16(1):93-5. PMID: 11709491.

Bottero V, Busuttil V, Loubat A, Magné N., Fischel JL, Milano G and Peyron JF. The topoisomerase poisons SN38 and doxorubicin activate NF-kB through the IKK complex. Cancer Research 2001, 61, 7785-7791. PMID: 11691793.

Bottero V, Rossi F, Samson M, Mari M, Hofman P and Peyron JF. IkB-a, the NF-kB inhibitory subunit, interacts with ANT, the mitochondrial ATP/ADP translocator. J Biol Chem. 2001;276(24):21317-24. PMID: 11287411.

Bottero V, Busuttil V, Frelin C, Imbert V and Peyron JF. Les facteurs de transcription NFkappaB: Des mécanismes moléculaires d'activation à la régulation de la survie et de la prolifération cellulaires. Regard sur la Biochimie 2001:31-39. (Review article in French).