Microbiology and Immunology Discipline

Center for Cancer Cell Biology, Immunology, and Infection

Dr. Sharma-Walia received her PhD in Experimental Medicine and Biotechnology from the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India in 1998. She was appointed as Senior Demonstrator in the Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India from 1998-2000. She worked as a postdoctoral fellow in the Northwestern University Medical School, Chicago in 2001 and the Department of Microbiology, Molecular Genetics and Immunology at the University of Kansas Medical Center (KUMC) from 2002-2005. She joined the ÎÞÂëȺ½» of Medicine and Science faculty in July 2005 as a Research Assistant Professor of Microbiology and Immunology and was promoted to Assistant Professor in July 2011, and subsequently to Associate Professor in July 2017.

Research

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), B cell lymphoproliferative primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV latent viral genome, viral gene expression, deregulated secretion of cytokines, and aggressive angiogenic factors are critical for KS, PEL, and MCD. Current treatments for KS and PEL rely on less effective cytotoxic systemic chemotherapeutics developed for non-virus-associated cancers that target DNA replication of all dividing cells. These treatment approaches have multiple myelosuppressive side effects, especially in immunocompromised patients. Hence, there is a critical need to design safe anti-viral therapies that simultaneously target tumors and eradicate viral load. Our long-term goal is to evaluate the role of arachidonic acid pathways of the host in KSHV biology. Our exciting studies discovered that 1) KSHV infection, aside from hijacking proinflammatory cyclooxygenase-2 and 5-lipoxygenase pathways, significantly reduce the secretion of anti-inflammatory lipoxin LXA4; 2) KSHV infected cells and human KS lesion cells express lipoxin receptor ALXR, and more importantly 3) Incubation of KSHV infected cells with stable small molecule analogs of LXA4s and aspirin-triggered lipoxins significantly downregulate KSHV's latent gene expression and decreases the infected cell survival. Currently, we are studying the role of host anti-inflammatory molecules in controlling KSHV replication and pathogenesis, which will lead to the effective treatment of KS and PEL. Understanding the antiviral and anticancer potential of anti-inflammatory lipoxins in KSHV biology is an unexplored field and can also be applied to other viral malignancies.

My lab also focuses on understanding the role of Arachidonic acid metabolism and the complexity of the tumor microenvironment in the biology of inflammatory breast cancer (IBC). Inflammatory breast cancer is the most aggressive, highly metastatic form of breast cancer. Systemic chemotherapy, adjuvant therapy, surgery, and radiation have not improved disease-free or overall survival of IBC patients. Inflammation, angiogenesis, metastasis, tumor-initiating cells, and circulating cancer stem cells are the signatures of IBC. The tumor microenvironment can suppress antitumor immunity, aggravate pro-inflammatory pro-tumorigenic factors, and eventually overcome the beneficial effects of the anti-cancer drugs and promote drug resistance. Therefore, it is very important to fully comprehend the role of the tumor microenvironment in breast cancer tumorigenesis to develop effective cancer therapies.

Peer-Reviewed Publications

• Bohae RL, May HP, Sharma-Walia N. Cyclopentenone prostaglandins: biologically active lipid mediators targeting inflammation. Front. Physiol. https://doi.org/10.3389/fphys.2021.640374. Review (published as corresponding author).
• Alsterda A, Asha K, Powrozek O, Repak M, Goswami S, Dunn AM, Memmel HC and Sharma-Walia N. Salubrinal Exposes Anticancer Properties in Inflammatory Breast Cancer Cells by Manipulating the Endoplasmic Reticulum Stress Pathway. Front. Oncol. https://doi.org/10.3389/fonc.2021.654940 (published as corresponding author).
• Asha K, Sharma-Walia N. Targeting Host Cellular Factors as a Strategy of Therapeutic Intervention for Herpesvirus Infections. Front. Cell. Infect. Microbiol. doi: 10.3389/fcimb.2021.603309. eCollection 2021.PMID: 33816328. Review (published as corresponding author).
• Iriana S, Asha K, Repak M, Sharma-Walia N. Hedgehog Signaling: Implications in Cancers and Viral Infections. Int J Mol Sci. 2021. doi: 10.3390/ijms22031042. PMID: 33494284. Review (published as corresponding author).
• Asha, K, N. Balfe, N Sharma-Walia. Concurrent Control of KSHV Life Cycle through Chromatin Modulation and Host Hedgehog Signaling: A New Prospect to the Therapeutic Potential of Lipoxin A4. J Virol., 2020; 94(9): e02177-19. PMCID: PMC7163125. (published as corresponding author).
• Valiya Veettil, M., G. Krishna, A. Roy, A. Ghosh, D. Dutta, B. Kumar, S. Chakraborty, A. T. Raveendran, N Sharma-Walia, B. Chandran. Kaposi's sarcoma Associated Herpesvirus Infection Induces the Expression of Neuroendocrine Genes in Endothelial Cells. J Virol., 2020. 94(8): e01692-19. PMCID: PMC7108831.
• Kumar B, Roy A, Asha K, Sharma-Walia N, Ansari MA, Chandran B. HACE1, an E3 ubiquitin-protein ligase, Mitigates Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Infection Induced Oxidative Stress by Promoting Nrf2 Activity. J Virol. 2019 Feb 20. pii: JVI.01812-18. doi: 10.1128/JVI.01812-18. ()
• Dutta A, Sharma-Walia N. Curbing Lipids: Impacts ON Cancer and Viral Infection. Int J Mol Sci. 2019 Feb 2;20(3). pii: E644. doi: 10.3390/ijms20030644. Review. () (published as corresponding author).
• Dajani S, Saripalli A, Sharma-Walia N. Water transport proteins-aquaporins (AQPs) in cancer biology. Oncotarget. 2018 Nov 20;9(91):36392-36405. doi: 10.18632/oncotarget.26351. eCollection 2018 Nov 20. Review. () (published as corresponding author).
• Asha K, Sharma-Walia N. Virus and tumor microenvironment induced ER stress and unfolded protein response: from complexity to therapeutics. Oncotarget. 2018 Aug 7;9(61):31920-31936. doi: 10.18632/oncotarget.25886. eCollection 2018 Aug 7. Review. () (published as corresponding author).
• Young KE, Flaherty S, Woodman KM, Sharma-Walia N, Reynolds JM. Fatty acid synthase regulates the pathogenicity of Th17 cells. J Leukoc Biol. 2017 Nov;102(5):1229-1235. doi: 10.1189/jlb.3AB0417-159RR. Epub 2017 Aug 28. ()
• Chandrasekharan JA, Huang XM, Hwang A, Sharma-Walia N. Altering the anti-inflammatory lipoxin microenvironment: a new insight into KSHV pathogenesis. J. Virol. 2016 Sep 28. pii: JVI.01491-16. () (published as corresponding author).
• Chandrasekharan JA, Marginean A, Sharma-Walia N. An insight into the role of arachidonic acid derived lipid mediators in virus associated pathogenesis and malignancies. Prostaglandins Other Lipid Mediat. 2016 Jul 20. pii: S1098-8823(16)30082-X. doi: 10.1016/j.prostaglandins.2016.07.009 () (published as corresponding author).
• Goswami S, Sharma-Walia N. Crosstalk between osteoprotegerin (OPG), fatty acid synthase (FASN) and, cycloxygenase-2 (COX-2) in breast cancer: implications in carcinogenesis. Oncotarget. 2016 Jun 6. doi: 10.18632/oncotarget.9835. () (published as corresponding author).
• Goswami S and Sharma-Walia N. Osteoprotegerin rich tumor microenvironment: implications in breast cancer. Oncotarget. doi: 10.18632/oncotarget.8658. April 8 2016. ()(published as corresponding author).
• Goswami S and Sharma-Walia N. Osteoprotegerin secreted by inflammatory and invasive breast cancer cells induces aneuploidy, cell proliferation and angiogenesis. BMC Cancer. 2015 Nov 25;15(1):935. doi: 10.1186/s12885-015-1837-1. () (published as corresponding author).
• Chandran K#, Goswami S, Sharma-Walia N#. Implications of a peroxisome proliferator-activated receptor alpha (PPARα) ligand clofibrate in breast cancer. Oncotarget. 2015 Nov 26. doi: 10.18632/oncotarget.6402. () # Both authors contributed equally to the work. (published as corresponding author).
• Chandrasekharan JA, Sharma-Walia N. Lipoxins: nature's way to resolve inflammation. J Inflamm Res. 2015 Sep 30;8:181-92. doi: 10.2147/JIR.S90380. eCollection 2015. ()(published as corresponding author).
• Marginean A#, Sharma-Walia N#. Lipoxins exert antiangiogenic and anti-inflammatory effects on Kaposi's sarcoma cells. Translational research : the journal of laboratory and clinical medicine. 2015. Epub 2015/03/31 () (Featured New Investigator series, published as corresponding author). # Both authors contributed equally to the work.
• Valiya Veettil M, Bottero V, Dutta D, Bandyopadhyay C, Gjyishi O, Sharma-Walia N, Dutta S, and Chandran B. Glutamate secretion and mGluR1 expression during Kaposi’s sarcoma associated herpesvirus infection promotes cell proliferation. PLoS Pathog. 2014 Oct 9; 10(10):e1004389. doi: 10.1371/journal.ppat.1004389. eCollection 2014 Oct. ()
• Sharma-Walia, N, Chandran K, Patel K, Veettil MV, and Marginean A. The KSHV induced 5-lipoxygenase-leukotriene B4 (5LO/LTB4) cascade plays key roles in KSHV latency, monocyte recruitment and lipogenesis. Journal of Virology, 2014; 85: 1980-1993 () (published as corresponding author).
• George-Paul A, Chandran B, Sharma-Walia N. COX-2-PGE2-EP receptor inflammatory axis: A key player in KSHV associated malignancies. Translational Research, 2013; 162(2):77-92. doi: 10.1016/j.trsl.2013.03.004. () (published as corresponding author).
• George-Paul A, Chandran B, Sharma-Walia N. Concurrent targeting of EP1/EP4 receptors and COX-2 induces synergistic apoptosis in KSHV and EBV associated non-Hodgkin lymphoma cell lines. Translational Research, 2013; 161(6):447-68. doi: 10.1016/j.trsl.2013.02.008 (Featured New Investigator series, () (published as corresponding author).
• Sharma-Walia N, Patel K, Chandran K, Marginean A, Bottero V, Kerur N, and George-Paul A. COX-2/PGE2: molecular ambassadors of Kaposi’s sarcoma-associated herpes virus oncoprotein-v-FLIP. Oncogenesis, 2012, 1, e5; doi:10.1038/oncsis.2012.5 (published as corresponding author). ()
• Sadagopan S, Veettil MV, Chakraborty S, Sharma-Walia N, Paudel N, Bottero V, and 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. ()
• George-Paul A, Sharma-Walia N and Chandran B. Targeting COX-2/KSHV latency and LANA-1/p53 links by nimesulide: A novel anti-viral/inflammatory/cancer strategy against Body cavity B cell lymphoma. PloS ONE, 2011. 6: e24379 () (published as corresponding author).
• Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S and Chandran B. IFI 16 acts as a nuclear danger sensor and induces the inflammasome in response to Kaposi's Sarcoma-Associated Herpes Virus (KSHV) Infection. Cell Host Microbe, 19:363-375, 2011. ()
• Bottero V, Kerur N, Sadagopan, S, Patel K, Sharma-Walia, N. and Chandran B. TGFβ Activating Kinase 1 (TAK1) phosphorylation and polyubiquitination is necessary for KSHV G protein-coupled receptor (vGPCR) activation of NF-ĸB. J. Virol.85, 1980-1993, 2011. ()
• Sharma-Walia N, George-Paul A, Patel K, Chandran K, Ahmad W and Chandran B. NFAT and CREB regulate Kaposi's Sarcoma-Associated Herpes Virus (KSHV) Induced Cyclooxygenase-2 (COX-2). J. Virol. 84, 12733-12753, 2010. () (published as corresponding author)
• Kerur N, Veettil, MV, Sharma-Walia N, Sadagopan, S, Bottero V, George-Paul A, Chandran B. Characterization of Entry and Infection of Monocytic THP-1 cells by Kaposi's Sarcoma-Associated Herpesvirus: Role of Heparan Sulfate, DC-SIGN, Integrins and Signaling. Virology, 406, 103-116. 2010 ()
• George-Paul A, Sharma-Walia N, Kerur N, White C and Chandran B. Piracy of PGE2/EP receptor mediated signaling by Kaposi's sarcoma associated herpes virus (KSHV/HHV-8) for latency gene expression: Strategy of a successful pathogen. Cancer Res. 70, 3697-3708, 2010 ()
• Sharma-Walia N*, George-Paul A, Bottero V, Sadagopan S, Veettil MV, Kerur N and Chandran B. Kaposi's Sarcoma-Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion. PloS Path. 6, P. e1000777, 2010 () (published as corresponding author)
  
  *This work was quoted as “” article by faculty of 1000.
• Bottero V, Sharma-Walia N, Kerur N, George-Paul A, Sadagopan S, Cannon M and Chandran B. Kaposi's 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, 392,34-51, 2009 ()
• Raghu H, Sharma-Walia N, Veettil MV, Sadagopan S and Chandran B. Kaposi's Sarcoma-Associated Herpes Virus Utilizes an Actin Polymerization-Dependant Macropinocytic Pathway To Enter Human Dermal Microvascular Endothelial and Human Umbilical Vein Endothelial Cells. J. Virol. 83, 4895-4911, 2009 ()
• Sadagopan S, Sharma-Walia N, Veettil MV, Bottero V, Levine R, Vart RJ and 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. 83,3342-3364,2009 ()
• Veettil MV, Sadagopan S, Sharma-Walia N, Wang FZ, Raghu H, Varga L and Chandran B. Kaposi’s Sarcoma-Associated Herpes Virus (KSHV/HHV-8) forms a Multi-Molecular Complex of Integrins (αVβ5, αVβ3 and α3β1) and CD98-xCT During Infection of Human Dermal Microvascular Endothelial (HMVEC-d) Cells and CD98-xCT is Essential for Post-Entry Stage of Infection. J. Virol. 82,12126-12144, 2008 ()
• Sivakumar R, Sharma-Walia, N, Raghu H, Veettil MV, Sadagopan S, Bottero V, Varga L, Levine R and Chandran B. Kaposi’s sarcoma Associated Herpes Virus 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. 82,1759-1776, 2008 ()
• Raghu H, Sharma-Walia N, Valiya VM, Sadagopan S, Caballero A, Sivakumar R, Varga L, Bottero V and Chandran B. Lipid Rafts of Primary Endothelial Cells are Essential for Kaposi’s Sarcoma-Associated Herpes Virus (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. 81,7941-7959, 2007 ()
• Sadagopan S, Sharma-Walia N, Veettil MV, Raghu H, Sivakumar R and Chandran B. Kaposi’s Sarcoma-Associated Herpes Virus (KSHV/HHV-8) Induces Sustained NF-kB Activation During de novo Infection of Primary Human Dermal Microvascular Endothelial Cells that is Essential for Viral Gene Expression. J. Virol. 81, 3949-3968, 2007 ()
• Veettil MV, Sharma-Walia N, Sadagopan S, Raghu H, Ramu S, Naranatt PP and Chandran B. RhoA-GTPase Facilitates Entry of Kaposi's Sarcoma-Associated Herpes Virus (KSHV/HHV-8) into the Adherent Target cells in a Src Dependent Manner.J. Virol. 80, 11432-11446, 2006 ()
• Sharma-Walia N, Raghu H, Sadagopan S, Ramu S, Veettil, MV, Naranatt PP, Smith M.M. and Chandran B. Cyclooxygenase-2 Induced by Kaposi's Sarcoma-Associated Herpes Virus Early during In Vitro Infection of Target Cells Plays a Role in the Maintenance of Latent Viral Gene Expression. J. Virol. 80, 6534-6552, 2006 ()
• Krishnan HH, Sharma-Walia N, Streblow DN, Naranatt PP and Chandran B. Focal Adhesion Kinase (FAK) is Critical for Kaposi's Sarcoma-Associated Herpes Virus (KSHV/HHV-8) Entry into the Target Cells. J. Virol. 80,1167-1180, 2006 ()
• Krishnan HH, Sharma-Walia N, Zeng L, Smith, MS and Chandran B. Envelope glycoprotein gB of Kaposi's Sarcoma-Associated Herpes Virus (KSHV) is essential for egress from infected cells. J. Virol. 79,10952-10967, 2005 ()
• Sharma-Walia N, Krishnan HH, Naranatt PP and Chandran B. KSHV/HHV-8 Envelope Glycoprotein gpK8.1A induced ERK Early During Infection is Essential for the Latent and Lytic gene Expression and for the Establishment of Latent Infection.J. Virol.79,10308-10329, 2005 ()

Book Chapters

• Kumar D, N Sharma-Walia, Kapoor S, and Tandon S. Antibody-Targeted Nanoparticles for Cancer Treatment. NanoBioMedicine. Springer, Singapore, 2020, pp 35-65.
• Everly D and Sharma-Walia N., Sadagopan, S. and Chandran, B. Herpesviruses and Cancer. In: Editor; E. Springer Sciences Business Media. (2011).
• Chandran B Sharma-Walia N. KSHV entry and infection of target cells. In: DNA tumor viruses. Springer Sciences Business Media; 2009.p.583-609.