Daniel R. Premkumar, PhD

  • Research Assistant Professor

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 doctorate 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

Glioblastoma is the most common and aggressive malignant brain tumor. As tumors evolve, the daughter cells often become molecularly heterogeneous and develop different functional properties and therapeutic vulnerabilities. Therapeutic resistance and relapse in glioblastoma relates to the extensive intratumoral genetic and phenotypic heterogeneity characteristic of these tumors. To improve therapeutic responses in glioma patients, new combination therapies and a mechanistic understanding of the inevitable emergence of drug resistance are needed.

To achieve more durable responses, Dr. Premkumar reasoned that targeting two or more fundamental processes that gliomas are particularly dependent upon could result in pleiotropic effects that would reduce the diversity of resistant subpopulations thereby enabling convergence to a more robust therapeutic strategy. Using a dose escalation protocol, he was able to select for resistance to histone deacetylase and proteasomal inhibitors. Interestingly, these resistant populations were indistinguishable from their drug-naïve counterparts with respect to morphology and growth rates. Conducting RNA Seq analyses, Dr. Premkumar identified significant changes in gene expression among resistant and drug-naïve cells.

Currently, his studies are aimed at understanding the molecular mechanisms of chemoresistance in glioma and working on the prospects of combining this knowledge with complementary approaches that could lead to the development of more robust therapeutic strategies for this critical unmet need.