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William Plunkett, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Bio Statement

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 1st 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 1st Sowell-Huggins Professorship in Cancer Research in that school.

Research Interests

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.

Office Address

The University of Texas MD Anderson Cancer Center
1901 East Road
Unit Number: 1950
Houston, TX 77054
Room Number: 3SCR3.4121
Phone: (713) 792-3335
Fax: (713) 794-4316
Email: wplunket@mdanderson.org

Education & Training

Degree-Granting Education

1970 University of Massachusetts, Amherst, MA, PHD, Biochemistry
1965 Springfield College, Springfield, MA, BS, Biology, Chemistry

Postgraduate Training

1972-1975 Research Associate, Microbiology, University of Colorado Medical Center, Denver, CO, Seymour S. Cohen, Ph.D.
1970-1971 Postdoctoral Fellow, Therapeutic Research, University of Pennsylvania, Philadelphia, PA, Seymour S. Cohen, Ph.D.

Experience/Service

Administrative Appointments/Responsibilities

Deputy Department Chair, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2008-present

Endowed Positions

Barnts Family Distinguished Chair for Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 1999-present

Honors and Awards

2011 Waun Ki Hong Achievement Award for Team Science - CLL, Division of Cancer Medicine
2006 1st Potu N. Rao Award for Outstanding Achievement in Basic Science, The University of Texas M. D. Anderson Cancer Center, Division of Cancer Medicine
2001 1st Sowell-Huggins Professorship in Cancer Research, University of Texas Graduate School of Biomedical Sciences, Houston
1999-present Barnts Family Distinguished Chair for Cancer Research, The University of Texas M. D. Anderson Cancer Center
1996 Faculty Achievement Award, Clinical Research, The University of Texas M. D. Anderson Cancer Center
1993 Chairman, Gordon Research Conference on Purines, Pyrimidines & Related Substances
1991 Outstanding Faculty Award, University of Texas Graduate School of Biomedical Sciences at Houston
1989-1999 Hubert L. and Olive Stringer Professorship in Medical Oncology, The University of Texas M. D. Anderson Cancer Center
1989 Service to Mankind Award, Leukemia Society of America, Gulf Coast Chapter
1988-1989 President of the Graduate Faculty, University of Texas Graduate School of Biomedical Sciences

Professional Memberships

American Association for Cancer Research
Chair, Program Committee, Mechanisms of Drug Action, 2004-2005
Member, Program Committee, Experimental and Molecular Therapeutics, 2004-2005
Chairman, Exhibits Committee, 2002-2005
Chairman, Research Fellowship Committee, 2002
Member, Education Committee, 2002
Chairman, 2002 Research Fellowships Committee, 2001-2002
Member, Program Committee, Experimental Therapeutics-2, 2001-2002
Chairman, Exhibits Committee, 2000
Member, C. P. Rhodes Memorial Award Committee, 1999
Member, Gertrude B. Elion Award Committee, 1999
Member, 1976

Selected Publications

Peer-Reviewed Original Research Articles

1. Liu X, Kantarjian H, Plunkett W. Sapacitabine for cancer. Expert Opin Investig Drugs 21(4):541-55, 4/2012. e-Pub 2/14/2012. PMCID: PMC3366487.
2. Liu X, Wang Y, Benaissa S, Matsuda A, Kantarjian H, Estrov Z, Plunkett W. Homologous recombination as a resistance mechanism to replication-induced double-strand breaks caused by the antileukemia agent CNDAC. Blood 116(10):1737-46, 9/2010. e-Pub 5/2010. PMCID: PMC2947394.
3. Chen R, Wierda WG, Chubb S, Hawtin RE, Fox JA, Keating MJ, Gandhi V, Plunkett W. Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood 113(19):4637-45, 5/2009. e-Pub 2/2009. PMCID: PMC2680368.

Grant & Contract Support

Title: Creating Novel Translation Inhibitors to Target Pro-Survival Oncoproteins
Funding Source: CPRIT-HIHR
Role: Co-Principal Investigator
Principal Investigator: Daniel Romo
Duration: 12/1/2012 - 11/30/2013
 
Title: Chronic Lymphocytic Leukemia Research Consortium
Funding Source: NIH
Role: Project Leader
Principal Investigator: Thomas Kipps
Duration: 9/24/2012 - 9/23/2017
 
Title: Sapacitabine therapy to create synthetic lethality in DNA repair-deficient CLL
Funding Source: NIH
Role: Co-Principal Investigator
Principal Investigator: William Wierda, Co-Principal Investigator
Duration: 8/1/2012 - 7/30/2015
 
Title: A Novel Preoperative Platform in Pancreatic Cancer for Mechanistic Studies
Funding Source: Lustgarten Foundation for Pancreatic Cancer Research
Role: Co-Investigator
Principal Investigator: Gauri Varadhachary
Duration: 5/1/2011 - 4/30/2013
 
Title: Biochemical Basis for Therapeutic Activity
Funding Source: NIH
Role: Principal Investigator
Duration: 1/1/2011 - 4/30/2016
 
Title: Center for Targeted Therapy Cancer Center Support (Core) Grant
Funding Source: NIH
Role: Co-Program Leader
Principal Investigator: Ronald DePinho
Duration: 7/1/2009 - 6/30/2014
 
Title: SPORE Grant in Leukemia
Funding Source: NIH
Role: Project Leader
Principal Investigator: Hagop Kantarjian
Duration: 12/1/2008 - 11/30/2013
 
Title: Development of New Drugs for CLL
Funding Source: US-European Alliance for CLL
Role: Principal Investigator
Duration: 3/10/2008 - 12/30/2012

Last updated: 11/28/2012