Sharmila Nair, PhD

Research Interests 

Glioblastoma multiform (GBM) tumors is one of the most aggressive primary brain tumor, and virtually all patients die within 2 years of diagnosis. Poor patient outcomes from GBM are multifactorial, including the presence of GBM stem cells (GSCs), which are resistant to radiation treatment and chemotherapy, and weak antitumor immunological responses. Overcoming resistance to immune checkpoint blockade and augmenting immune responses that suppress tumor growth is a therapeutic priority in GBM. Zika virus has a unique capability to target and lyse GSCs which opened the field of glioblastoma research to using the oncolytic capacity of Zika virus to treat GBM. Our laboratory focuses on leveraging the unique tropism of Zika virus (ZIKV) and the host immune system to target/lyse glioblastoma tumors as well as understand how therapeutic ZIKV treatment in brain tumors improves anti-tumor immune responses. Our research interests are aimed at

  1. Understanding mechanisms by which ZIKV improves immunological responses against glioblastoma tumors.
  2. Identify critical residues on ZIKV genome that mediate oncolytic efficacy against Glioblastoma Stem cells.
  3. Developing and testing immune therapies that provides better success in targeting glioblastoma tumors in combination with oncolytic ZIKV therapy.

 

Publications

Nair S, Mazzoccoli L, Jash A, Govero J, Bais SS, Hu T, Fontes-Garfias CR, Shan C, Okada H, Shresta S, Rich JN, Shi PY, Diamond MS, Chheda MG. Zika virus oncolytic activity requires CD8+ T cells and is boosted by immune checkpoint blockade. JCI Insight. 2020 Nov 24;. doi: 10.1172/jci.insight.144619. Epub 2021 PMID: 33232299

Winkler ES, Bailey AL, Kafai NM, Nair S, McCune BT, Yu J, Fox JM, Chen RE, Earnest JT, Keeler SP, Ritter JH, Kang LI, Dort S, Robichaud A, Head R, Holtzman MJ, Diamond MS. SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function. Nat Immunol. 2020 Nov;21(11):1327-1335. doi: 10.1038/s41590-020-0778-2. Epub 2020 Aug 24. PMID: 32839612

Zhang R, Kim AS, Fox JM, Nair S, Basore K, Klimstra WB, Rimkunas R, Fong RH, Lin H, Poddar S, Crowe JE Jr, Doranz BJ, Fremont DH, Diamond MS.Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature. 2018 May;557(7706):570-574. doi: 10.1038/s41586-018-0121-3. Epub 2018 May 16. PMID: 29769725

Nair S, Huynh JP, Lampropoulou V, Loginicheva E, Esaulova E, Gounder AP, Boon ACM, Schwarzkopf EA, Bradstreet TR, Edelson BT, Artyomov MN, Stallings CL, Diamond MS. Irg1 expression in myeloid cells prevents immunopathology during M. tuberculosis infection. J Exp Med. 2018 Apr 2;215(4):1035-1045. doi: 10.1084/jem.20180118 Epub 2018 Mar 6. PMID: 29511063

Nair S, Poddar S, Shimak RM, Diamond MS. Interferon Regulatory Factor 1 Protects against Chikungunya Virus-Induced Immunopathology by Restricting Infection in Muscle Cells. J Virol. 2017 Nov 15;91(22). doi: 10.1128/JVI.01419-17. Print 2017 Nov 15. PMID: 28835505

Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SC, Griss T, Weinheimer CJ, Khader S, Randolph GJ, Pearce EJ, Jones RG, Diwan A, Diamond MS, Artyomov MN. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab. 2016 Jul 12;24(1):158-66. doi: 10.1016/j.cmet.2016.06.004. Epub 2016 Jun 30. PMID: 27374498

Kurhade C, Zegenhagen L, Weber E, Nair S, Michaelsen-Preusse K, Spanier J, Gekara NO, Kröger A, Överby AK. Type I Interferon response in olfactory bulb, the site of tick-borne flavivirus accumulation, is primarily regulated by IPS-1. J Neuroinflammation. 2016 Jan 27;13:22. doi: 10.1186/s12974-016-0487-9. PMID: 26819220

Nair S, Diamond MS. Innate immune interactions within the central nervous system modulate pathogenesis of viral infections. Curr Opin Immunol. 2015 Oct;36:47-53. doi: 10.1016/j.coi.2015.06.011. Epub 2015 Jul 8. Review. PMID: 26163762

Weber E, Finsterbusch K, Lindquist R, Nair S, Lienenklaus S, Gekara NO, Janik D, Weiss S, Kalinke U, Överby AK, Kröger A. Type I interferon protects mice from fatal neurotropic infection with Langat virus by systemic and local antiviral responses. J Virol. 2014 Nov;88(21):12202-12. doi: 10.1128/JVI.01215-14. Epub 2014 Aug 13. PMID: 25122777

Nair S, Michaelsen-Preusse K, Finsterbusch K, Stegemann-Koniszewski S, Bruder D, Grashoff M, Korte M, Köster M, Kalinke U, Hauser H, Kröger A. Interferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons. PLoS Pathog. 2014 Mar;10(3):e1003999. doi: 10.1371/journal.ppat.1003999. eCollection 2014 Mar. PMID: 24675692

Nandakumar R, Finsterbusch K, Lipps C, Neumann B, Grashoff M, Nair S, Hochnadel I, Lienenklaus S, Wappler I, Steinmann E, Hauser H, Pietschmann T, Kröger A. Hepatitis C virus replication in mouse cells is restricted by IFN-dependent and -independent mechanisms.Gastroenterology.2013 Dec;145(6):1414- 23.e1. doi: 10.1053/j.gastro.2013.08.037. Epub 2013 Aug 21. PMID: 23973921