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Improved therapeutic response via metabolic modulation. Development of a safe and reproducible method to selectively acidify and deenergize the human cancers. Specifically, we seek to employ the natural tendency of cancers to convert glucose to lactate as a method for selective intracellular acidification, which is known to potentiate tumor response to chemotherapy, radiation therapy, hyperthermia, and photodynamic therapy. In vivo 31P and 1H MRS demonstrated that human cancer xenografts such as melanoma, breast, prostate, ovarian and glioma in immunosuppressed mice treated with metabolic modulators exhibit a sustained and tumor-selective decrease in pH, bioenergetics and increase in lactate and subsequent sensitization to chemo- and radiation therapy.ExpertiseMouse xenograft development, tumor cells studies, drug delivery, metabolomics, and tumor micro-environment modulation. Surface coil development to perform MRI/MRS studies on preclinical models. 1H, 31P, 13C MRS.T1, T2, DTI, DCE MRI. Measurement of test-retest reproducibility of SUV on PET in cancer patients.
Zhang Q, Wang HY, Liu X, Cruz SN, Jillab M, Melnikov O, Nath K, Glickson J, Wasik MA: Cutting Edge: ROR1/CD19 Receptor Complex Promotes Growth of Mantle Cell Lymphoma Cells Independently of the B Cell Receptor-BTK Signaling Pathway The Journal of Immunology 203 (8): 2043-2048,2019.
Lee SC, Shestov AA, Guo L, Zhang Q, Roman JC, Liu X, Wang HY, Pickup S, Nath K, Lu P, Hofbauer S, Mesaros C, Wang YL, Nelson DS, Schuster SJ, Blair IA, Glickson JD, Wasik MA: Metabolic Detection of Bruton's Tyrosine Kinase Inhibition in Mantle Cell Lymphoma Cells Molecular cancer research 17 (6): 1365-1377,2019.
Xu HN, Feng M, Nath K, Nelson DS, Roman J, Zhao H, Lin Z, Glickson JD, Li LZ: Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts Molecular imaging and biology 21 (3): 426-435,2019.
*Nath K, Roman J, Nelson DS, Guo L, Lee SC, Orlovskiy S, Muriuki K, Heitjan DF, Leeper DB, Blair IA, Putt ME, Glickson JD: Effect of Differences in Metabolic Activity of Melanoma Models on Response to Lonidamine plus Doxorubicin Scientific reports 8 (1): 14654,2018 *Corresponding Author.
Zhou R, Bagga P, Nath K, Hariharan H, Mankoff D and Reddy R: Glutamate-weighted Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging Detects Glutaminase Inhibition in a Mouse Model of Triple Negative Breast Cancer Cancer research 78 (19): 5521-5526,2018.
*Nath K, Nelson DS, Roman J, Putt ME, Lee SC, Leeper DB, Glickson JD: Effect of Lonidamine on Systemic Therapy of DB-1 Human Melanoma Xenografts with Temozolomide Anticancer research 37 (7): 3413-3421,2017 *Corresponding Author.
Choi H, Liu T, Nath K, Zhou R, Chen IW: Peptide nanoparticle with pH-sensing cargo solubility enhances cancer drug efficiency Nano today 13 : 15-22,2017.
*Nath K, Guo L, Nancolas B, Nelson DS, Shestov AA, Lee SC, Roman J, Zhou R, Leeper DB, Halestrap AP, Blair IA, Glickson JD: Mechanism of antineoplastic activity of lonidamine BBA Reviews on Cancer 1866 (2): 151-162,2016 *Corresponding Author.
*Nath K, Nelson DS, Putt ME, Leeper DB, Garman B, Nathanson KL, Glickson JD: Comparison of the Lonidamine Potentiated Effect of Nitrogen Mustard Alkylating Agents on the Systemic Treatment of DB-1 Human Melanoma Xenografts in Mice PLoS One 11 (6): 2016 *Corresponding Author.
Guo L, Shestov AA, Worth AJ, Nath K, Nelson DS, Leeper DB, Glickson JD, Blair IA: Inhibition of mitochondrial complex II by the anti-cancer agent lonidamine Journal of Biological Chemistry 291 (1): 42-57,2016.
B6 Blockley Hall423 Guardian DrivePerelman School of MedicineDepartment of RadiologyUniversity of Pennsylvania