Daniel R. Premkumar, PhD

Research Assistant Professor


Daniel Premkumar

Contact

412-692-9227

Biography

Prior to joining the faculty of the Department of Neurological Surgery at the University of Pittsburgh in 2008, Daniel R. Premkumar, PhD, was a senior scientist at a biotechnology company. He graduated from Madurai Kamaraj University in India where he earned his masters and PhD degrees. Dr. Premkumar then completed his post-doctoral training at Case Western Reserve University in Cleveland.

Dr. Premkumar has published more than 40 papers in refereed journals and has been awarded patents to characterize protein-protein interaction biosensors for cellular systems biology profiling. He is currently examining the efficacy of promising various receptor inhibitors, for inhibiting glioma proliferation in vitro, using genotypically diverse panel of malignant glioma cell lines to identify potential genotype-response associations.

Specialized Areas of Interest

Major research emphasis is directed towards understanding the molecular mechanisms of receptor tyrosine kinase inhibition and signaling in malignant human glioma cell lines.

Professional Organization Membership

American Association for Cancer Research
American Society of Pharmacology and Experimental Therapeutics

Education & Training

BS, Biology, Madura College, 1982
MS, Animal Sciences, Madurai Kamaraji University, 1984
PhD, Entomology, Madurai Kamaraji University, 1990

Selected Publications

Jane EP, Premkumar DR, Cavaleri JM, Sutera PA, Rajasekar T, Pollack IF. Dinaciclib, a Cyclin-Dependent Kinase Inhibitor Promotes Proteasomal Degradation of Mcl-1 and Enhances ABT-737-Mediated Cell Death in Malignant Human Glioma Cell Lines. J Pharmacol Exp Ther 356(2):354-65, 2016.

Foster KA, Jane EP, Premkumar DR, Morales A, Pollack IF. NVP-BKM120 potentiates apoptosis in tumor necrosis factor-related apoptosis-inducing ligand-resistant glioma cell lines via upregulation of Noxa and death receptor 5. Int J Oncol 47(2):506-16, 2015.

Premkumar DR, Jane EP, Pollack IF. Cucurbitacin-I inhibits Aurora kinase A, Aurora kinase B and survivin, induces defects in cell cycle progression and promotes ABT-737-induced cell death in a caspase-independent manner in malignant human glioma cells. Cancer Biol Ther 16(2):233-43, 2015.

Foster KA, Jane EP, Premkumar DR, Morales A, Pollack IF. Co-administration of ABT-737 and SAHA induces apoptosis, mediated by Noxa upregulation, Bax activation and mitochondrial dysfunction in PTEN-intact malignant human glioma cell lines. J Neurooncol 120(3):459-72, 2014.

Jane EP, Premkumar DR, Morales A, Foster KA, Pollack IF. Inhibition of phosphatidylinositol 3-kinase/AKT signaling by NVP-BKM120 promotes ABT-737-induced toxicity in a caspase-dependent manner through mitochondrial dysfunction and DNA damage response in established and primary cultured glioblastoma cells. J Pharmacol Exp Ther 350(1):22-35, 2014.

Premkumar DR, Jane EP, Foster KA, Pollack IF. Survivin inhibitor YM-155 sensitizes tumor necrosis factor- related apoptosis-inducing ligand-resistant glioma cells to apoptosis through Mcl-1 downregulation and by engaging the mitochondrial death pathway. J Pharmacol Exp Ther 346(2):201-10, 2013.

Jane EP, Premkumar DR, DiDomenico JD, Hu B, Cheng SY, Pollack IF. YM-155 potentiates the effect of ABT-737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context. Mol Cancer Ther 12(3):326-38, 2013.

Premkumar DR, Jane EP, DiDomenico JD, Vukmer NA, Agostino NR, Pollack IF. ABT-737 synergizes with bortezomib to induce apoptosis, mediated by Bid cleavage, Bax activation, and mitochondrial dysfunction in an Akt-dependent context in malignant human glioma cell lines. J Pharmacol Exp Ther 341(3):859-72, 2012.

Premkumar DR, Jane EP, Agostino NR, DiDomenico JD, Pollack IF. Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage. Mol Carcinog 52(2):118-33, 2013.

Jane EP, Premkumar DR, Pollack IF. Bortezomib sensitizes malignant human glioma cells to TRAIL, mediated by inhibition of the NF-{kappa}B signaling pathway. Mol Cancer Ther 10(1):198-208, 2011.

A complete list of Dr. Premkumar's publications can be reviewed through the National Library of Medicine's publication database.

Research Activities

Malignant human gliomas are highly invasive primary tumors with poor prognosis despite advances in multimodality therapy. Glioma accounts for 30% of brain cancer, and 80% of gliomas are malignant. Glioma is characterized by uncontrolled cellular proliferation, diffuse infiltration, necrosis, and resistance to apoptosis. Several genes such as TP53, PTEN, CDKN2A, and EGFR, altered in glial tumorigenesis.

The molecular and genetic aberrations in glioma have been extensively studied and show remarkable heterogeneity even within an individual tumor, which facilitate therapeutic resistance in the tumor cells via various signaling pathways. Thus, new therapeutic approaches are urgently needed.

We have identified several critical “nodes’ for cell death signaling (including NF-κB, proteasomes, AKT and Bcl-2 family proteins), when inhibited, promoted apoptotic signaling in glioma cells. Currently, our group is working on to understand the molecular mechanisms that are integrally involved in mediating glioma resistance to apoptotic signaling.