Warren Jackson (Jack) Pledger is a molecular cell biologist who is a Professor, Department of Surgery, University of Utah School of Medicine and a member of the Cell Response and Regulation Program, Huntsman Cancer Institute. He was the Associate Center Director for Basic Science at the Moffitt Cancer Center and Research Institute. He has held academic appointments and tenure at the University of North Carolina School of Medicine (Assistant and Associate Professor of Pharmacology and Program Leader of the Cell Biology Program at the Lineberger Cancer Center), Vanderbilt University School of Medicine (Professor of Cell Biology) and the University of South Florida College of Medicine (Professor of Biochemistry and Oncology).
Pledger was born in Philadelphia, Pennsylvania, and was reared in Texas. He earned his Bachelor’s and Master’s degrees in Biology from the University of Houston. He completed his graduate work at Purdue University, where he received a Ph.D. in Molecular Biology. He had postdoctoral fellowships at the University of Texas/M.D. Anderson Cancer Center in Houston and the Dana Farber Cancer Institute in Boston.
He moved to the Moffitt Cancer Center in 1994 as Associate Center Director for Basic Research and was awarded the Cortner-Couch Endowed Chair in Cancer Research. Dr. Pledger was responsible for the development, administration and quality of all research programs and cores at Moffitt. He was also responsible for recruiting investigators to Moffitt to support the application for a National Cancer Institute (NCI) Comprehensive Cancer Center. Moffitt grew into a national research institution during his tenure as Associate Center Director for Basic Sciences. He instituted and developed the Moffitt Research Institute and was its Founding Director. Moffitt/University of South Florida Ph.D. program in Cancer Biology was organized under his leadership, which continues to train students. He also served as the Deputy Center Director (2001 to 2013). In addition, he served as the principal investigator at Moffitt’s National Functional Genomics Center (NFGC).
Pledger has received peer-reviewed funding for more than 30 years. He has held numerous National Institute of Health (NIH) and NCI grants, participated in three Program Project Grants (PPG) and was the principal investigator of one PPG. He has served as the principal investigator on several institutional grants including the American Cancer Society (ACS) Institutional Research Grant, the National Genomics Center Grant (Department of Defense), and a U56 / U54 partnership grant with the Ponce School of Medicine Cancer Center. He has over 150 publications in journals, including Science, Nature, Proceedings of the National Academy of Sciences, USA, Molecular Cell Biology, and Journal of Cell Biology. Dr. Pledger was also an associate editor for the Journal of Cellular Biochemistry, Critical Reviews in Eukaryotic Gene Expression and Cancer Research. He has served as a permanent member on NIH, ACS and VA grant review panels and has served on several NIH and NCI ad hoc panels that reviewed Program Project Grants and Center Grants. He was the first recipient of Moffitt Cancer Center's Scientist of the Year Award.
Pledger's research focuses on the mechanisms governing cell cycle progression. He was the first to show that the cell cycle is regulated by a series of sequential events and to hypothesize that dysfunction of these events could trigger transformation or cancer. He demonstrated that growth factors controlled cell cycle regulatory events and has actively studied these processes, including platelet derived growth factor (PDGF) and insulin-like growthfactor-1 (IGF-1) signal transduction. He investigated the role of growth factor-regulated cyclin-dependent kinase (CDK) activity in the control of cellular proliferation, and used mouse models to explore the role of CDK activity in tumor formation. His current projects address the impact of signal transduction pathway inhibition on CRC tumor cell survival, and the hallmarks of cancer during the evolution of tumor progression seeking to find new therapeutic avenues.
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- Lin SL Kikuchi T Pledger WJ Tamm I. Interferon inhibits the establishment of competence in Go/S-phase transition. Science. 1986 Jul 18;233(4761):356-9. PMID 3726533.
- Pledger WJ Thompson WJ Strada SJ. Mediation of serum-induced changes in cyclic nucleotide levels in cultured fibroblasts by cyclic nucleotide phosphodiesterase. Nature. 1975 Aug 28;256(5520):729-31. PMID 168501.
- Olashaw NE Pledger WJ. Association of platelet-derived growth factor-induced protein with nuclear material. Nature. 1983 Nov 17-23;306(5940):272-4. PMID 6646209.
- Bowman T Broome MA Sinibaldi D Wharton W Pledger WJ Sedivy JM Irby R Yeatman T Courtneidge SA Jove R. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7319-24. Epub 2001 Jun 12. PMID 11404481.
- Drozdoff V Wall NA Pledger WJ. Expression and growth inhibitory effect of decapentaplegic Vg-related protein 6: evidence for a regulatory role in keratinocyte differentiation. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5528-32. PMID 7515504.
- Selinfreund RH Barger SW Pledger WJ Van Eldik LJ. Neurotrophic protein S100 beta stimulates glial cell proliferation. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3554-8. PMID 1902567.
- Olashaw NE O'Keefe EJ Pledger WJ. Platelet-derived growth factor modulates epidermal growth factor receptors by a mechanism distinct from that of phorbol esters. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3834-8. PMID 3012534.
- Russell WE Van Wyk JJ Pledger WJ. Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2389-92. PubMed PMID 6371813.
- Wharton W Leof E Pledger WJ O'Keefe EJ. Modulation of the epidermal growth factor receptor by platelet-derived growth factor and choleragen: effects on mitogenesis. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5567-71. PMID 6291052.
- Pledger WJ Hart CA Locatell KL Scher CD. Platelet-derived growth factor-modulated proteins: constitutive synthesis by a transformed cell line. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4358-62. PMID 6170062.
- Clemmons DR Van Wyk JJ Pledger WJ. Sequential addition of platelet factor and plasma to BALB/c 3T3 fibroblast cultures stimulates somatomedin-C binding early in cell cycle. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6644-8. PMID 6161369.
- Stiles CD Capone GT Scher CD Antoniades HN Van Wyk JJ Pledger WJ. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1279-83. PMID 312500.
- Pledger WJ Stiles CD Antoniades HN Scher CD. An ordered sequence of events is required before BALB/c-3T3 cells become committed to DNA synthesis. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2839-43. PMID 275855.
- Pledger WJ Stiles CD Antoniades HN, Scher CD. Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481-5. PMID 270695.
- Kazi A, Carie A, Blaskovich MA, Bucher C, Thai V, Moulder S, Peng H, Carrico D, Pusateri E, Pledger WJ, Berndt N, Hamilton A, Sebti SM. Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 Phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy. Mol Cell Biol. 2009 Apr;29(8):2254-63. PMID 19204084.
- Herman B, Pledger WJ. Platelet-derived growth factor-induced alterations in vinculin and actin distribution in BALB/c-3T3 cells. J Cell Biol. 1985 Apr;100(4):1031-40. PMID 3920222.
- H. Lee Moffitt Cancer Center & Research Institute
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- O'Keefe EJ, Pledger WJ. A model of cell cycle control: sequential events regulated by growth factors. Mol Cell Endocrinol. 1983 Aug;31(2-3):167-86. Review. PMID 6313447.
- Jackson RJ, Adnane J, Coppola D, Cantor A, Sebti SM, Pledger WJ. Loss of the cell cycle inhibitors p21(Cip1) and p27(Kip1) enhances tumorigenesis in knockout mouse models. Oncogene. 2002 Dec 5;21(55):8486-97. PMID 12466968.
- Pledger WJ, Hart CA, Wharton WR. Mammalian cell proliferation is regulated by the synergistic actions of multiple growth factors. Adv Exp Med Biol. 1981;138:287-300. PMID 7200718.
- Olashaw N, Pledger WJ. Paradigms of growth control: relation to Cdk activation. Sci STKE. 2002 May 28;2002(134):re7. Review. PMID 12034920.