Molecular and Therapeutics Unit

The foundation for the development of effective cancer therapeutics depends on hypothesis-driven basic science research and its translation to clinical endeavors. Glioblastoma (GBM) is the most common malignant primary brain tumor. It remains incurable despite aggressive, multimodal therapy and has proven to be an enduring challenge. In the Molecular & Therapeutics Unit, we extensively study the pathophysiology of GBM in the context of potential therapeutic candidates using preclinical in vivo and in vitro GBM models.

Our lab has three major goals:

  1. Identify and validate novel therapeutic targets for GBM.
  2. Develop biological and/or small molecule agents to target the validated therapeutic candidates.
  3. Drug repurposing.

Lab Members:

Lab Alumni
  • Hannah Sur, BS, Medical Student at Quinnipiac University 
  • Sriya Namagiri, BS, Medical Student at St. George's University 
  • Jean-Paul Bryant, MD, MPH, MS, Neurosurgery resident at MedStar Georgetown University Hospital
Selected Publications:

Otani Y, Yoo JY, Lewis CT, Chao S, Swanner J, Shimizu T, Kang JM, Murphy SA, Rivera-Caraballo K, Hong B, Glorioso JC, Nakashima H, Lawler SE, Banasavadi-Siddegowda Y, Heiss JD, Yan Y, Pei G, Caligiuri MA, Zhao Z, Chiocca EA, Yu J, Kaur B (2022)
NOTCH-Induced MDSC Recruitment after oHSV Virotherapy in CNS Cancer Models Modulates Antitumor Immunotherapy.
Clin Cancer Res, 28:1460-1473. PubMed ID: 35022322

Shah AH, Govindarajan V, Doucet-O'Hare TT, Rivas S, Ampie L, DeMarino C, Banasavadi-Siddegowda YK, Zhang Y, Johnson KR, Almsned F, Gilbert MR, Heiss JD, Nath A (2022)
Differential expression of an endogenous retroviral element [HERV-K(HML-6)] is associated with reduced survival in glioblastoma patients.
Sci Rep, 12:6902. PubMed ID: 35477752

Bryant, J-P; Levy, A; Heiss, JD; Banasavadi-Siddegowda, YK. Review of PP2A Tumor Biology and Antitumor Effects of PP2A Inhibitor LB100 in the Nervous System. Cancers 2021, 13(12), 3087; https://doi.org/10.3390/cancers1312308

Abdulmalik, S; Ramos, D; Rudraiah, S; Banasavadi-Siddegowda, YK; Kumbar, S. The glucagon-like peptide 1 receptor agonist Exendin-4 induces tenogenesis in human mesenchymal stem cells.Differentiation (2021); DOI: 10.1016/j.diff.2021.05.001

Otani Y, Sur HP, Rachaiah G, Namagiri S, Chowdhury A, Lewis CT, Shimizu T, Gangaplara A, Wang X, Vézina A, Maric D, Jackson S, Yan Y, Zhengping Z, Ray-Chaudhury A, Kumar S, Ballester LY, Chittiboina P, Yoo JY, Heiss J, Kaur B, Banasavadi-Siddegowda YK (2021)
Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma.
Neuro Oncol, 23:1481-1493. PubMed ID: 33556161

Bryant JP, Heiss J, Banasavadi-Siddegowda YK (2021)
Arginine Methylation in Brain Tumors: Tumor Biology and Therapeutic Strategies.
Cells, 10 PubMed ID: 33440687

Nair M, Khosla MOtani YYeh M, Park FShimizu TKang JM, Bolyard CYu J-GBanasavadi-Siddegowda YKLopez GKaur BPollock RELee TJOld MYoo JY. Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation. 2020 Apr 23;12(4):1040. DOI: 10.3390/cancers12041040. PMID: 32340193.

Tedros S, Kondrasov A, Namagiri S, Chowdhury A, Banasavadi-Siddegowda YK, Ray-Chaudhury A. Pathological features of tumors of the nervous system in hereditary cancer predisposition syndromes: a review. Neurosurgery. 2020 (NEU-D-20-01169R3).

Yoo JY, Swanner J, Otani Y, Nair M, Park F, Banasavadi-Siddegowda Y, Liu J, Jaime-Ramirez AC, Hong B, Geng F, Guo D, Bystry D, Phelphs M, Quadri H, Lee TJ, Kaur B (2019)
Oncolytic HSV therapy increases trametinib access to brain tumors and sensitizes them in vivo.
Neuro Oncol, 21:1131-1140. PubMed ID: 31063549

Lee TJ, Nair M, Banasavadi-Siddegowda Y, Liu J, Nallanagulagari T, Jaime-Ramirez AC, Guo JY, Quadri H, Zhang J, Bockhorst KH, Aghi MK, Carbonell WS, Kaur B, Yoo JY (2019)
Enhancing Therapeutic Efficacy of Oncolytic Herpes Simplex Virus-1 with Integrin β1 Blocking Antibody OS2966.
Mol Cancer Ther, 18:1127-1136. PubMed ID: 30926634

Hong B, Muili K, Bolyard C, Russell L, Lee TJ, Banasavadi-Siddegowda Y, Yoo JY, Yan Y, Ballester LY, Bockhorst KH, Kaur B (2019)
Suppression of HMGB1 Released in the Glioblastoma Tumor Microenvironment Reduces Tumoral Edema.
Mol Ther Oncolytics, 12:93-102. PubMed ID: 30719499

Russell L, Swanner J, Jaime-Ramirez AC, Wang Y, Sprague A, Banasavadi-Siddegowda Y, Yoo JY, Sizemore GM, Kladney R, Zhang J, Lehman NL, Ostrowski MC, Hong B, Caligiuri M, Yu J, Kaur B (2018)
PTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance.
Nat Commun, 9:5006. PubMed ID: 30479334

Banasavadi-Siddegowda YK, Welker AM, An M, Yang X, Zhou W, Shi G, Imitola J, Li C, Hsu S, Wang J, Phelps M, Zhang J, Beattie CE, Baiocchi R, Kaur B (2018)
PRMT5 as a druggable target for glioblastoma therapy.
Neuro Oncol, 20:753-763. PubMed ID: 29106602

Kesanakurti D, Maddirela D, Banasavadi-Siddegowda YK, Lai TH, Qamri Z, Jacob NK, Sampath D, Mohanam S, Kaur B, Puduvalli VK (2017)
A novel interaction of PAK4 with PPARγ to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma.
Oncogene, 36:5309-5320. PubMed ID: 28534509

Jaime-Ramirez AC, Dmitrieva N, Yoo JY, Banasavadi-Siddegowda Y, Zhang J, Relation T, Bolyard C, Wojton J, Kaur B (2017)
Humanized chondroitinase ABC sensitizes glioblastoma cells to temozolomide.
J Gene Med, 19 PubMed ID: 28087981

Bolyard C, Meisen WH, Banasavadi-Siddegowda Y, Hardcastle J, Yoo JY, Wohleb ES, Wojton J, Yu JG, Dubin S, Khosla M, Xu B, Smith J, Alvarez-Breckenridge C, Pow-Anpongkul P, Pichiorri F, Zhang J, Old M, Zhu D, Van Meir EG, Godbout JP, Caligiuri MA, Yu J, Kaur B (2017)
BAI1 Orchestrates Macrophage Inflammatory Response to HSV Infection-Implications for Oncolytic Viral Therapy.
Clin Cancer Res, 23:1809-1819. PubMed ID: 27852701

Banasavadi-Siddegowda YK, Russell L, Frair E, Karkhanis VA, Relation T, Yoo JY, Zhang J, Sif S, Imitola J, Baiocchi R, Kaur B (2017)
PRMT5-PTEN molecular pathway regulates senescence and self-renewal of primary glioblastoma neurosphere cells.
Oncogene, 36:263-274. PubMed ID: 27292259

Bhallamudi VP, Xue R, Purser CM, Presley KF, Banasavadi-Siddegowda YK, Hwang J, Kaur B, Hammel PC, Poirier MG, Lannutti JJ, Pandian RP (2016)
Nanofiber-based paramagnetic probes for rapid, real-time biomedical oximetry.
Biomed Microdevices, 18:38. PubMed ID: 27106026

Yan F, Alinari L, Lustberg ME, Martin LK, Cordero-Nieves HM, Banasavadi-Siddegowda Y, Virk S, Barnholtz-Sloan J, Bell EH, Wojton J, Jacob NK, Chakravarti A, Nowicki MO, Wu X, Lapalombella R, Datta J, Yu B, Gordon K, Haseley A, Patton JT, Smith PL, Ryu J, Zhang X, Mo X, Marcucci G, Nuovo G, Kwon CH, Byrd JC, Chiocca EA, Li C, Sif S, Jacob S, Lawler S, Kaur B, Baiocchi RA (2014)
Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma.
Cancer Res, 74:1752-65. PubMed ID: 24453002

Gu C, Banasavadi-Siddegowda YK, Joshi K, Nakamura Y, Kurt H, Gupta S, Nakano I (2013)
Tumor-specific activation of the C-JUN/MELK pathway regulates glioma stem cell growth in a p53-dependent manner.
Stem Cells, 31:870-81. PubMed ID: 23339114

Joshi K, Banasavadi-Siddegowda Y, Mo X, Kim SH, Mao P, Kig C, Nardini D, Sobol RW, Chow LM, Kornblum HI, Waclaw R, Beullens M, Nakano I (2013)
MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells.
Stem Cells, 31:1051-63. PubMed ID: 23404835

Guvenc H, Pavlyukov MS, Joshi K, Kurt H, Banasavadi-Siddegowda YK, Mao P, Hong C, Yamada R, Kwon CH, Bhasin D, Chettiar S, Kitange G, Park IH, Sarkaria JN, Li C, Shakhparonov MI, Nakano I (2013)
Impairment of glioma stem cell survival and growth by a novel inhibitor for Survivin-Ran protein complex.
Clin Cancer Res, 19:631-42. PubMed ID: 23251006

Saxena A, Banasavadi-Siddegowda YK, Fan Y, Bhattacharya S, Roy G, Giovannucci DR, Frizzell RA, Wang X (2012)
Human heat shock protein 105/110 kDa (Hsp105/110) regulates biogenesis and quality control of misfolded cystic fibrosis transmembrane conductance regulator at multiple levels.
J Biol Chem, 287:19158-70. PubMed ID: 22505710

Banasavadi-Siddegowda YK, Mai J, Fan Y, Bhattacharya S, Giovannucci DR, Sanchez ER, Fischer G, Wang X (2011)
FKBP38 peptidylprolyl isomerase promotes the folding of cystic fibrosis transmembrane conductance regulator in the endoplasmic reticulum.
J Biol Chem, 286:43071-80. PubMed ID: 22030396

Siddegowda YK, Leo MD, Kumar D, Hooda OK, Prakash VR, Mishra SK (2007)
Influence of heat stress on the reactivity of isolated chicken carotid artery to vasoactive agents.
Exp Physiol, 92:1077-86. PubMed ID: 17720746

Leo MD, Siddegowda YK, Kumar D, Tandan SK, Sastry KV, Prakash VR, Mishra SK (2008)
Role of nitric oxide and carbon monoxide in N(omega)-Nitro-L-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery.
Eur J Pharmacol, 596:111-7. PubMed ID: 18713623