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
ASPET (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

Gliomas are the most common primary tumors in adult central nervous system. Malignant glioblastoma is characterized by rapid cell proliferation, high invasion and genetic alterations. Despite advances in all these treatment modalities with aggressive surgical resection combined with irradiation and chemotherapy, the median survival remains poor. During malignant transformation, several genetic alterations are involved in glioma oncogenesis, including inactivation of tumor suppressor genes such as p16, Rb, p53 and PTEN, and amplification and overexpression of the CDK4 and EGFR genes. Avoiding apoptosis is integral to tumor development and resistance to therapy.  The main goal of researchers is to elucidate links that exist between survival signaling and cell cycle regulatory pathways, and to exploit this information to develop novel therapeutic approaches to the treatment of glioblastoma. 

During the cell division cycle, mitotic entry, spindle assembly, chromosome segregation and cytokinesis must all be carefully coordinated to ensure that the two daughter cells inherit all the genetic material required for further growth and development. When this process is disrupted, it can lead to cancer. Central to this coordination are several prominent protein kinases. A major area of interest to this group involves mechanistically understanding the regulatory function of Aurora kinases and cyclin dependent kinases (CDKs) in cell cycle regulation and how deregulation contributes to carcinogenesis. In another project, we explore the factors that regulate inactivation of the NF-κB pathway by proteasomal inhibitor, bortezomib in malignant human glioma cells and determining the mechanisms by which interruption of this process may lead to enhanced cell killing. Recently, it has been shown that interference of this pathway—genetically or pharmacologically—dramatically increases TRAIL and HDAC inhibitor-mediated apoptosis. In another project, the potential benefit of combining the CDK inhibitor dinaciclib with the Bcl-2/Bcl-xL antagonist ABT-737 has been demonstrated, and the advantages of simultaneously targeting both survival pathways in patients with glioma has been highlighted.