Primary Appointment

Dual/Joint/Adjunct Appointment

William Plunkett, Ph.D., Professor at The University of Texas MD Anderson Cancer Center, holds the Barnts Family Distinguished Chair for Cancer Research. His administrative appointment is Deputy Chairman, Department of Experimental Therapeutics.  

His major research pursuits are related to development of novel therapeutics based on knowledge of cellular responses to DNA damage, and elucidating the mechanisms of drug action, particularly of nucleoside analogs. His investigations demonstrated multiple mechanism of action for both fludarabine and gemcitabine, as well as the mechanisms of other nucleosides.  He has enjoyed sustained and dedicated collaborations with his colleagues involved with clinical research, interactions that have resulted in advances in clinical treatments that induce remissions more effectively and are maintained then longer than previously possible in leukemias. He was the recipient of the Service to Mankind Award from the Leukemia Society of America in 1989, the Faculty Achievement Award in Clinical Research in 1996, and the 1^st Potu N. Rao award for Excellence in Basic Research in 2006, and the Waun Ki Hong Achievement Award for Team Research - CLL in 2011. He was elected a Fellow of the American Association for the Advancement of Science in 2012.  He also has the title of Associate Vice President, Research Integrity, and is the Institutional Research Integrity Officer.

Dr. Plunkett is particularly interested in education of the next generation of scientists. He has been a member of the University of Texas Graduate School of Biomedical Sciences at Houston since 1976. His activities in graduate education have been recognized by his election to President of the Faculty of The Graduate School of Biomedical Sciences, and the award of the 1^st Sowell-Huggins Professorship in Cancer Research in that school.

My research program melds discovery of mechanisms of drug action and an understanding of cancer cell biology to generate experimental strategies that improve therapeutic efficacy and aim to overcome potential means of tumor resistance. I have concentrated efforts on translational investigations with colleagues in the Leukemia Department. 

Inhibition of DNA Repair. We have discovered that the mechanism of action of a nucleoside analogue now in early phase clinical trials, sapacitabine, is to generate a single strand break which is difficult to repair, and results in formation of a double-strand DNA break upon subsequent DNA replication.  A homologous recombination mechanism is required to repair such lesions.  Based on this information, we have initiated investigations of sapacitabine in tumors that lack the homologous recombination repair functions.

Cellular context as a basis for specificity.  The survival of CLL is dependent upon the sustained expression of anti-apoptotic proteins, some of which (Mcl-1, XIAP) have intrinsic signals for rapid turnover of transcripts and protein. We reasoned that transient inhibition of transcription would decrease these proteins to the point of initiation of apoptosis, an irreversible process. Transcription requires phosphorylation of RNA polymerase II by cyclin-dependent kinase 9. Our investigations in primary CLL samples demonstrated that cyclin-dependent kinase inhibitors flavopiridol and SNS-032 potently inhibited this enzyme, with a resulting decrease in polymerase phosphorylation, transcript generation and decreased survival protein levels, that were associated with apoptosis induction within 8 hr. This has provided rationale for a multi-center clinical trial, coordinated at MDACC, of SNS-032.

Administrative Appointments/Responsibilities

Endowed Positions

Last updated: 11/28/2012