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Helen Piwnica-Worms, Ph.D.

Present Title & Affiliation

Primary Appointment

Vice Provost of Science and Professor, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Senator A.M. Aikin Jr. Distinguished Chair, The University of Texas MD Anderson Cancer Center, Houston, TX

Bio Statement

Dr. Piwnica-Worms assumed the role of Vice Provost of Science and Professor of Cancer Biology at MDACC in 2013. Dr. Piwnica-Worms completed a B.A. in Biology at St. Olaf College (1979), a Ph.D. degree in microbiology and immunology at Duke University Medical School (1984) and a postdoctoral fellowship in pathology at the Dana-Farber Cancer Institute (1988). Dr. Piwnica-Worms was Instructor of Pathology at Harvard Medical School and Dana-Farber Cancer Institute from 1988-1989 prior to moving to Tufts University Medical School where she was Assistant Professor of Physiology (1989-1992) followed by Harvard Medical School and Beth Israel Hospital, Boston where she was Assistant and then Associate Professor of Microbiology and Molecular Genetics (1992-1994). In 1994, Dr. Piwnica-Worms moved to Washington University School of Medicine in St. Louis where she was the Gerty T. Cori Professor and Chair of Cell Biology and Physiology and Professor of Internal Medicine. She also served as Associate Director of Basic Science at the Alvin J. Siteman Cancer Center and co-directed the BRIGHT Institute at Washington University.

Research Interests

The major goals of my research program are to delineate how the cell division cycle is regulated in unperturbed cycling cells (cell cycle control); how cell division is delayed by replicative- and genotoxic-stress (checkpoint control); how cancer cells derail these regulatory pathways and ultimately; to use this information to treat human disease. Clinical, preclinical and basic studies in breast and prostate cancer are a major focus of the laboratory. We are actively involved in designing and analyzing the results of Phase I/II clinical trials aimed at translating our fundamental knowledge of cell cycle- and checkpoint-control into improved targeted therapies for breast cancer patients. Recognizing that a key challenge facing breast cancer researchers today is the lack of good preclinical models for studying human breast cancer, we are working with primary human breast tumors obtained directly from breast cancer patients. These tumors are being propagated in the humanized mammary fat pads of immune compromised mice for our preclinical studies (HIM models). Many of these models metastasize out of the mouse mammary gland to distant mouse organs, including bone and lung. We are identifying the molecular changes associated with the acquisition of metastasis in this model. In addition, we are developing mouse models that enable regulatory pathways to be studied non-invasively and repetitively in living mice using molecular imaging strategies, with a particular focus on p21 and CDC25A.

Research Interest:

Cell Cycle- and Checkpoint-Control

Perturbations in Cell Cycle- and Checkpoint-Control in Cancer                                                                                                                                                                        Therapeutic strategies for treating p53-deficient tumors

Office Address

The University of Texas MD Anderson Cancer Center
1400 Pressler
Unit Number: 1492
Houston, TX 77030
Room Number: FCT20.5223
Phone: 713-745-1221

Education & Training

Degree-Granting Education

1984 Duke University, Durham, NC, PHD, Microbiology and Immunology, Laboratory of Jack D. Keene
1979 St. Olaf College, Northfield, MN, BA, magna cum laude, Biology

Postgraduate Training

1984-1988 Postdoctoral Fellowship, Research Fellow in Pathology, Laboratory of Thomas M. Roberts, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA

Selected Publications

Peer-Reviewed Original Research Articles

1. Ma CX, Ellis MJ, Petroni GR, Guo Z, Cai SR, Ryan CE, Craig Lockhart A, Naughton MJ, Pluard TJ, Brenin CM, Picus J, Creekmore AN, Mwandoro T, Yarde ER, Reed J, Ebbert M, Bernard PS, Watson M, Doyle LA, Dancey J, Piwnica-Worms H, Fracasso PM. A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Breast Cancer Res Treat 137(2):483-92, 1/2013. e-Pub 12/2012. PMCID: PMC3539064.
2. Huh J, Piwnica-Worms H. CRL4(CDT2) targets CHK1 for PCNA-independent destruction. Mol Cell Biol 33(2):213-26, 1/2013. e-Pub 10/2012. PMCID: PMC3554108.
3. Origanti S, Cai SR, Munir AZ, White LS, Piwnica-Worms H. Synthetic lethality of Chk1 inhibition combined with p53 and/or p21 loss during a DNA damage response in normal and tumor cells. Oncogene 32(5):577-88, 1/2013. e-Pub 3/2012. PMCID: PMC3381958.
4. Duxin JP, Moore HR, Sidorova J, Karanja K, Honaker Y, Dao B, Piwnica-Worms H, Campbell JL, Monnat RJ, Stewart SA. Okazaki fragment processing-independent role for human Dna2 enzyme during DNA replication. J Biol Chem 287(26):21980-91, 6/2012. e-Pub 5/2012. PMCID: PMC3381158.
5. Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding WS, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Leitch M, Hunt K, Olson J, Tao Y, Maher CA, Fulton LL, Fulton RS, Harrison M, Oberkfell B, Du F, Demeter R, Vickery TL, Elhammali A, Piwnica-Worms H, McDonald S, Watson M, Dooling DJ, Ota D, Chang LW, Bose R, Ley TJ, Piwnica-Worms D, Stuart JM, Wilson RK, Mardis ER. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486(7403):353-60, 6/2012. e-Pub 6/2012. PMCID: PMC3383766.
6. Ma CX, Cai S, Li S, Ryan CE, Guo Z, Schaiff WT, Lin L, Hoog J, Goiffon RJ, Prat A, Aft RL, Ellis MJ, Piwnica-Worms H. Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models. J Clin Invest 122(4):1541-52, 4/2012. e-Pub 3/2012. PMCID: PMC3314455.
7. Tinkum KL, Marpegan L, White LS, Sun J, Herzog ED, Piwnica-Worms D, Piwnica-Worms H. Bioluminescence imaging captures the expression and dynamics of endogenous p21 promoter activity in living mice and intact cells. Mol Cell Biol 31(18):3759-72, 9/2011. e-Pub 7/2011. PMCID: PMC3165732.
8. Wang YV, Leblanc M, Fox N, Mao JH, Tinkum KL, Krummel K, Engle D, Piwnica-Worms D, Piwnica-Worms H, Balmain A, Kaushansky K, Wahl GM. Fine-tuning p53 activity through C-terminal modification significantly contributes to HSC homeostasis and mouse radiosensitivity. Genes Dev 25(13):1426-38, 7/2011. PMCID: PMC3134085.
9. Fracasso PM, Williams KJ, Chen RC, Picus J, Ma CX, Ellis MJ, Tan BR, Pluard TJ, Adkins DR, Naughton MJ, Rader JS, Arquette MA, Fleshman JW, Creekmore AN, Goodner SA, Wright LP, Guo Z, Ryan CE, Tao Y, Soares EM, Cai SR, Lin L, Dancey J, Rudek MA, McLeod HL, Piwnica-Worms H. A Phase 1 study of UCN-01 in combination with irinotecan in patients with resistant solid tumor malignancies. Cancer Chemother Pharmacol 67(6):1225-37, 6/2011. e-Pub 8/2010. PMCID: PMC3102212.
10. Ma CX, Janetka JW, Piwnica-Worms H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol Med 17(2):88-96, 2/2011. PMID: 21087899.
11. Lee G, Origanti S, White LS, Sun J, Stappenbeck TS, Piwnica-Worms H. Contributions made by CDC25 phosphatases to proliferation of intestinal epithelial stem and progenitor cells. PLoS One 6(1):e15561, 2011. e-Pub 1/2011. PMCID: PMC3026785.
12. Lennerz JK, Hurov JB, White LS, Lewandowski KT, Prior JL, Planer GJ, Gereau RW, Piwnica-Worms D, Schmidt RE, Piwnica-Worms H. Loss of Par-1a/MARK3/C-TAK1 kinase leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis. Mol Cell Biol 30(21):5043-56, 11/2010. PMCID: PMC2953066.
13. Honaker Y, Piwnica-Worms H. Casein kinase 1 functions as both penultimate and ultimate kinase in regulating Cdc25A destruction. Oncogene 29(23):3324-34, 6/2010. PMCID: PMC2883652.
14. Qian Z, Leung-Pineda V, Xuan B, Piwnica-Worms H, Yu D. Human cytomegalovirus protein pUL117 targets the mini-chromosome maintenance complex and suppresses cellular DNA synthesis. PLoS Pathog 6(3):e1000814, 3/2010. PMCID: PMC2841624.
15. Granot Z, Swisa A, Magenheim J, Stolovich-Rain M, Fujimoto W, Manduchi E, Miki T, Lennerz JK, Stoeckert CJ, Meyuhas O, Seino S, Permutt MA, Piwnica-Worms H, Bardeesy N, Dor Y. LKB1 regulates pancreatic beta cell size, polarity, and function. Cell Metab 10(4):296-308, 10/2009. PMCID: PMC2790403.
16. Lin J, Hou KK, Piwnica-Worms H, Shaw AS. The polarity protein Par1b/EMK/MARK2 regulates T cell receptor-induced microtubule-organizing center polarization. J Immunol 183(2):1215-21, 7/2009. PMCID: PMC2837933.
17. Leung-Pineda V, Huh J, Piwnica-Worms H. DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress. Cancer Res 69(6):2630-7, 3/2009. e-Pub 3/2009. PMCID: PMC2776040.
18. Lee G, White LS, Hurov KE, Stappenbeck TS, Piwnica-Worms H. Response of small intestinal epithelial cells to acute disruption of cell division through CDC25 deletion. Proc Natl Acad Sci U S A 106(12):4701-6, 3/2009. PMCID: PMC2660721.
19. Watkins JL, Lewandowski KT, Meek SE, Storz P, Toker A, Piwnica-Worms H. Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association. Proc Natl Acad Sci U S A 105(47):18378-83, 11/2008. PMCID: PMC2587537.
20. Lovly CM, Yan L, Ryan CE, Takada S, Piwnica-Worms H. Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379. Mol Cell Biol 28(19):5874-85, 10/2008. PMCID: PMC2547006.
21. Nakajima H, Yonemura S, Murata M, Nakamura N, Piwnica-Worms H, Nishida E. Myt1 protein kinase is essential for Golgi and ER assembly during mitotic exit. J Cell Biol 181(1):89-103, 4/2008. PMCID: PMC2287290.
22. Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung MC, Piwnica-Worms H. GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell 13(1):36-47, 1/2008. PMCID: PMC2276649.
23. Hurov J, Piwnica-Worms H. The Par-1/MARK family of protein kinases: from polarity to metabolism. Cell Cycle 6(16):1966-9, 8/2007. PMID: 17721078.
24. Tarakanova VL, Leung-Pineda V, Hwang S, Yang CW, Matatall K, Basson M, Sun R, Piwnica-Worms H, Sleckman BP, Virgin HW. Gamma-herpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication. Cell Host Microbe 1(4):275-86, 6/2007. PMCID: PMC2034359.
25. Hurov JB, Huang M, White LS, Lennerz J, Choi CS, Cho YR, Kim HJ, Prior JL, Piwnica-Worms D, Cantley LC, Kim JK, Shulman GI, Piwnica-Worms H. Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo. Proc Natl Acad Sci U S A 104(13):5680-5, 3/2007. PMCID: PMC1838456.
26. King JB, Gross J, Lovly CM, Piwnica-Worms H, Townsend RR. Identification of protein phosphorylation sites within Ser/Thr-rich cluster domains using site-directed mutagenesis and hybrid linear quadrupole ion trap Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom 21(21):3443-51, 2007. PMID: 17918214.
27. Dequiedt F, Martin M, Von Blume J, Vertommen D, Lecomte E, Mari N, Heinen MF, Bachmann M, Twizere JC, Huang MC, Rider MH, Piwnica-Worms H, Seufferlein T, Kettmann R. New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases. Mol Cell Biol 26(19):7086-102, 10/2006. PMCID: PMC1592903.
28. Leung-Pineda V, Ryan CE, Piwnica-Worms H. Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit. Mol Cell Biol 26(20):7529-38, 10/2006. PMCID: PMC1636880.
29. Chen YM, Wang QJ, Hu HS, Yu PC, Zhu J, Drewes G, Piwnica-Worms H, Luo ZG. Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity. Proc Natl Acad Sci U S A 103(22):8534-9, 5/2006. e-Pub 5/2006. PMCID: PMC1482526.
30. King JB, Gross J, Lovly CM, Rohrs H, Piwnica-Worms H, Townsend RR. Accurate mass-driven analysis for the characterization of protein phosphorylation. Study of the human Chk2 protein kinase. Anal Chem 78(7):2171-81, 4/2006. PMID: 16579595.
31. Ferguson AM, White LS, Donovan PJ, Piwnica-Worms H. Normal cell cycle and checkpoint responses in mice and cells lacking Cdc25B and Cdc25C protein phosphatases. Mol Cell Biol 25(7):2853-60, 4/2005. PMCID: PMC1061644.
32. Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L, Mansukhani M, Murty VV, Gaciong Z, Meek SE, Piwnica-Worms H, Hibshoosh H, Parsons R. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 7(2):193-204, 2/2005. PMID: 15710331.
33. Luker KE, Smith MC, Luker GD, Gammon ST, Piwnica-Worms H, Piwnica-Worms D. Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. Proc Natl Acad Sci U S A 101(33):12288-93, 8/2004. PMCID: PMC514471.
34. Meek SE, Lane WS, Piwnica-Worms H. Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. J Biol Chem 279(31):32046-54, 7/2004. PMID: 15161933.
35. Hurov JB, Watkins JL, Piwnica-Worms H. Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr Biol 14(8):736-41, 4/2004. PMID: 15084291.
36. Chen MS, Ryan CE, Piwnica-Worms H. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol Cell Biol 23(21):7488-97, 11/2003. PMCID: PMC207598.
37. Neely KE, Piwnica-Worms H. Cdc25A regulation: to destroy or not to destroy--is that the only question? Cell Cycle 2(5):455-7, Sep-Oct, 9/2003. PMID: 12963843.
38. Bulavin DV, Higashimoto Y, Demidenko ZN, Meek S, Graves P, Phillips C, Zhao H, Moody SA, Appella E, Piwnica-Worms H, Fornace AJ. Dual phosphorylation controls Cdc25 phosphatases and mitotic entry. Nat Cell Biol 5(6):545-51, 6/2003. PMID: 12766774.
39. Schwarz JK, Lovly CM, Piwnica-Worms H. Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation. Mol Cancer Res 1(8):598-609, 6/2003. PMID: 12805407.
40. Zhao H, Watkins JL, Piwnica-Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci U S A 99(23):14795-800, 11/2002. e-Pub 10/2002. PMCID: PMC137498.
41. Luker GD, Sharma V, Pica CM, Dahlheimer JL, Li W, Ochesky J, Ryan CE, Piwnica-Worms H, Piwnica-Worms D. Noninvasive imaging of protein-protein interactions in living animals. Proc Natl Acad Sci U S A 99(10):6961-6, 5/2002. e-Pub 5/2002. PMCID: PMC124511.
42. Chen F, Zhang Z, Bower J, Lu Y, Leonard SS, Ding M, Castranova V, Piwnica-Worms H, Shi X. Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A 99(4):1990-5, 2/2002. PMCID: PMC122307.
43. Rothblum-Oviatt CJ, Ryan CE, Piwnica-Worms H. 14-3-3 binding regulates catalytic activity of human Wee1 kinase. Cell Growth Differ 12(12):581-9, 12/2001. PMID: 11751453.
44. Müller J, Ory S, Copeland T, Piwnica-Worms H, Morrison DK. C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1. Mol Cell 8(5):983-93, 11/2001. PMID: 11741534.
45. Crawford DF, Piwnica-Worms H. The G(2) DNA damage checkpoint delays expression of genes encoding mitotic regulators. J Biol Chem 276(40):37166-77, 10/2001. e-Pub 8/2001. PMID: 11483598.
46. Deming PB, Cistulli CA, Zhao H, Graves PR, Piwnica-Worms H, Paules RS, Downes CS, Kaufmann WK. The human decatenation checkpoint. Proc Natl Acad Sci U S A 98(21):12044-9, 10/2001. PMCID: PMC59764.
47. Zhao H, Piwnica-Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol 21(13):4129-39, 7/2001. PMCID: PMC87074.
48. Chen MS, Hurov J, White LS, Woodford-Thomas T, Piwnica-Worms H. Absence of apparent phenotype in mice lacking Cdc25C protein phosphatase. Mol Cell Biol 21(12):3853-61, 6/2001. PMCID: PMC87049.
49. Hurov JB, Stappenbeck TS, Zmasek CM, White LS, Ranganath SH, Russell JH, Chan AC, Murphy KM, Piwnica-Worms H. Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase. Mol Cell Biol 21(9):3206-19, 5/2001. PMCID: PMC86958.
50. Graves PR, Lovly CM, Uy GL, Piwnica-Worms H. Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding. Oncogene 20(15):1839-51, 4/2001. PMID: 11313932.
51. Ahn JY, Schwarz JK, Piwnica-Worms H, Canman CE. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res 60(21):5934-6, 11/2000. PMID: 11085506.

Grant & Contract Support

Title: Combined Targeting of Chk1 and PARP to Triple Negative Breast Cancer
Funding Source: Susan G. Komen for the Cure
Role: Principal Investigator
Duration: 7/1/2012 - 6/30/2016
 
Title: Project 2: Imaging and Characterizing Stress Responses In Vivo with p21 Reporter Mice (H. Piwnica-Worms, PI)
Funding Source: NIH/NCI
Role: Co-Principal Investigator
Principal Investigator: Piwnica-Worms, David
Duration: 1/1/2012 - 12/31/2017

Last updated: 2/19/2014