Texas Tech University Health Sciences CenterPhD Candidate
Aug. 2014 - May. 2018Amarillo, TexasDissertation Title: “Rational redox-driven multi-targeted drug discovery for human brain tumors”
Adviser: Kalkunte Srivenugopal
The focus of my doctoral studies had been mainly anticancer drug discovery followed by evaluation of pharmacokinetics, safety, and efficacy in preclinical cancer models especially on glioblastoma.
• Worked on at least 4 small molecules such as O6-benzylguanine, disulfiram, m-nitroaspirin etc., that inhibit a DNA damage response protein, MGMT, and show synergy with chemotherapy in preclinical brain cancer models. • Developed and evaluated the efficiency of non-diuretic, brain penetrating analog of ethacrynic acid for its oxidative stress-based cancer-selective potent anticancer effects in orthotopic intracranial models. Developed an LC-MS/MS method to study the penetration, distribution, and elimination kinetics of the drug in mice. • Designed and characterized an NQO1 activatable drug for its potent anticancer activity in intracranial xenograft models and demonstrated its ability to activate immune system (immunogenic cell death) through induction of redox stress mediated ER stress, unfolded protein response (UPR) employing in vivo vaccination, flux analysis, transition electron microscopy (TEM) and FACS • Designed and developed an alpha-ketoglutarate analog inspired by the prognostic and survival benefits associated with IDH mutant patients and evaluated its role in epigenetics, DNA damage response in vitro, and in vivo anticancer effects and elucidated its MOA.