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Rong Chen, BS, MS, Ph.D,

Present Title & Affiliation

Primary Appointment

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

Bio Statement

I majored in Biochemistry in Wuhan University in Wuhan, China where I got my Bachelor in Sciences degree. During my undergraduate study I was awarded a small grant to conduct a study of producing single cell protein from corn wastes through mixed micro-organisms culturing. This study was published in 1994. After college, I went to Institute of Genetics of Chinese Academy of Sciences in Beijing for a Master degree in molecular biology. My study focused on molecular cloning and expression of proteinase inhibitors. These natural proteinase inhibitors protect plants from insect damage. Once transfected and expressed in other crops, they can make these crops resistant to insects. In 1996, I came to University of Texas Graduate school of Biomedical Sciences. My Ph.D. study was directed by Dr. Arly Nelson. My work focused on organic cation transporters in the secretion of nucleoside analogs. Using frog oocyte as an in vitro expression system, I found some nucleosides are transported by organic cation transporters. Different organic cation transporters had different specificity. Further, chimeric transporters were regenerated to identify the domains that contribute to its specificity. After graduation, I came to Dr. William Plunkett's lab as a postdoctoral fellow. I am now an instructor in Dr. Plunkett's lab. My work focuses on developing transcription/translation inhibitors in cancer therapy and overcoming drug resistance.

Research Interests

 

The major focus of my research is developing inhibitors of transcription/translation for the therapy of cancer. Some tumors are dependent upon the continued activity of a single oncogene for maintenance of their malignant phenotype. This has been characterized as "oncogene addiction". We hypothesized that strategies that decrease expression of critical oncogene products by transcription/translational inhibitors will have therapeutic benefit. The biological context of dependence of the oncogene for survival, and the short intrinsic half-life of the mRNA/protein of the oncogene would provide the specificity for this therapy. Small molecular cyclin dependent kinase inhibitors such as flavopiridol, roscovitine, SNS-032 that are active in transcriptional control, transcription inhibitor Actinomycin D,  as well as translational inhibitor Homoharringtonine have been evaluated in our lab in leukemia cell systems such CML, CLL and mantle cell lymphoma. They are effective in inducing apoptosis in these systems through the transcriptional /translational inhibition of oncoproteins such as Bcr-Abl, Mcl-1 and Cyclin D1. Currently, our studies focus on developing new transcription/translation inhibitors, as well as evaluating these inhibitors in overcoming resistance to conventional therapy.

Office Address

The University of Texas MD Anderson Cancer Center
1901 East Road
Unit Number: 1950
Houston, TX 77054
Room Number: 4SCR3.1049

Education & Training

Degree-Granting Education

2002 University of Texas Health Science Center, Graduate School of Biomedical Sciences, Houston, TX, PHD, Cancer Biology
1995 Chinese Academy of Sciences, Institute of Genetics, Beijing, P. R. China, MS, Molecular Biology
1992 Wuhan University, Wuhan, P. R. China, BS, Biochemistry

Postgraduate Training

2002-3/2007 Postdoctoral Fellowship, molecular pharmacology, The University of Texas MD Anderson Cancer Center, Houston, TX, Dr. William Plunkett

Experience/Service

Academic Appointments

Assistant Professor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 12/2010-present

Honors and Awards

2009 Best poster award, Gordon Research Conferences, Nucleosides, Nucleotides & Oligonucleotides
2006 The Kimberly Patterson Fellowship in Leukemia Research
2003-2005 Aventis Translational Research Fellowship Award

Selected Publications

Peer-Reviewed Original Research Articles

1. Liu H, Zhang T, Chen R, McConkey DJ, Ward JF, Curley SA. Multiple kinase pathways involved in the different de novo sensitivity of pancreatic cancer cell lines to 17-AAG. J Surg Res 176(1):147-53, 7/2012. e-Pub 10/2011. PMID: 22099584.
2. Carter BZ, Mak DH, Shi Y, Fidler JM, Chen R, Ling X, Plunkett W, Andreeff M. MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in a murine model of AML. Leukemia 26(3):443-50, 3/2012. e-Pub 9/2011. PMID: 21904380.
3. Zecevic A, Sampath D, Ewald B, Chen R, Wierda W, Plunkett W. Killing of chronic lymphocytic leukemia by the combination of fludarabine and oxaliplatin is dependent on the activity of XPF endonuclease. Clin Cancer Res 17(14):4731-41, 7/2011. e-Pub 6/2011. PMID: 21632856.
4. Chen R, Guo L, Chen Y, Jiang Y, Wierda WG, Plunkett W. Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia. Blood 117(1):156-64, 1/2011. e-Pub 10/2010. PMID: 20971952.
5. Chen R, Chubb S, Cheng T, Hawtin RE, Gandhi V, Plunkett W. Responses in mantle cell lymphoma cells to SNS-032 depend on the biological context of each cell line. Cancer Res 70(16):6587-97, 8/2010. e-Pub 7/2010. PMCID: PMC2929954.
6. Tong WG, Chen R, Plunkett W, Siegel D, Sinha R, Harvey RD, Badros AZ, Popplewell L, Coutre S, Fox JA, Mahadocon K, Chen T, Kegley P, Hoch U, Wierda WG. Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma. J Clin Oncol 28(18):3015-22, 6/2010. e-Pub 5/2010. PMID: 20479412.
7. Kurtova AV, Balakrishnan K, Chen R, Ding W, Schnabl S, Quiroga MP, Sivina M, Wierda WG, Estrov Z, Keating MJ, Shehata M, Jäger U, Gandhi V, Kay NE, Plunkett W, Burger JA. Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance. Blood 114(20):4441-50, 11/2009. e-Pub 9/2009. PMID: 19762485.
8. 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.
9. Qin T, Youssef EM, Jelinek J, Chen R, Yang AS, Garcia-Manero G, Issa JP.. Effect of cytarabine and decitabine in combination in human leukemic cell lines. Clin Cancer Res 13(14):4225-4232, 2007. PMID: 17634552.
10. Chen R, Gandhi V, Plunkett W. A sequential blockade strategy for the design of combination therapies to overcome oncogene addiction in chronic myelogenous leukemia. Cancer Res 66(22):10959-10966, 2006. PMID: 17108134.
11. Chen R, Keating MJ, Gandhi V, Plunkett W. Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood 106(7):2513-2519, 2005. e-Pub 6/2005. PMCID: PMC1895272.
12. Chen R, Jonker JW, Nelson JA. Renal organic cation and nucleoside transport. Biochem Pharmacol 64(2):185-190, 2002. PMID: 12123738.
13. Chen R, Nelson JA. Role of organic cation transporters in the renal secretion of nucleosides. Biochem Pharmacol 60(2):215-219, 2000. PMID: 10825466.
14. Chen R, Pan BF, Sakurai M, Nelson JA. A nucleoside-sensitive organic cation transporter in opossum kidney cells. Am J Physiol 276(2 Pt 2):F323-328, 2/1999. PMID: 9950964.
15. Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA. A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci 47(2):181-186, 2/1999. PMID: 10220855.
16. Zhou Z, Zhu Z, Chen R, Liu C, Li X. High level expression of oryzacystatin in Escherichia coli. Chin J Biotechnol 12(1):17-24, 1996. PMID: 8877110.
17. Zhou ZL, Zhu Z, Liu CM, Chen R, Xiao GF, Li XH. Molecular cloning of thiol-proteinase inhibitor gene. High Technology Letters 2(2):89-94, 1996.
18. Xie Z, Chen R. Producing single cell protein from corn wastes through mixed micro-organisms culturing. Cereal & Food Industry 7:28-31, 1994.

Invited Articles

1. Chen R, Plunkett W. Strategy to induce apoptosis and circumvent resistance in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol 23(1):155-66, 3/2010. PMID: 20620979.
2. Chen R, Plunkett W. Sequential Blockade of Oncogenic Kinases. American Association for Cancer Research 96th Annual Meeting Educational Book:344-348, 2005.

Abstracts

1. Chen R, Tsai J, Chen Y, Burrows F, Wierda W and Plunkett W. Mechanism of action of the multikinase inhibitor TG02 in chronic lymphocytic leukemia. Proceedings of America Association for Cancer Research 53, 4/2012.
2. Chen R, Chen Y, Green SR, Wierda WG, Plunkett W. A novel derivative of the Cdk inhibitor roscovitine that induces apoptosis in CLL and overcomes stromal cell-mediated protection. Proceedings of America Association for Cancer Research 51 (#4431), 2010.
3. Guo L, Chen R, Wierda WG, Plunkett W. Homoharringtonine downregulates Mcl-1 and induces apoptosis in Chronic Lymphocytic Leukemia cells. Proceedings of American Association for Cancer Research 50 (#1815), 2009.
4. Chen R,Chubb S, Cheng T, Hawtin RE, Fox JA, Gandhi V, Plunkett W. SNS-032 reduced the expression of cyclin D1 and Mcl-1 and inhibited survival in mantle cell lymphoma cell lines. Proceedings of America Association for Cancer Research 50 (#1801), 2009.
5. Wierda WG, Chen R, Plunkett W, Coutre S, Badros A, Popplewell L, Fox JA, Hoch U, Goldberg Z. A phase 1 trial of SNS-032, a potent and specific cdk 2, 7 and 9 inhibitor, in chronic lymphocytic leukemia and multiple myeloma. Blood 110 (#3178), 2008.
6. Chen R, Chubb S, Hoch U, Hawtin RE, Fox JA, Gandhi V, Plunkett W. SNS-032, a novel inhibitor of cyclin-dependent kinases 2, 7 and 9, blocks transcription of cyclin D1 and Mcl-1, causing cell death in mantle cell lymphoma cell lines. Proceedings of American Association for Cancer Research 49 (#756), 2008.
7. Chen R, Wierda WG, Chubb S, Hoch U, 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: comparison with flavopiridol. Blood 109 (#3112), 2007.
8. Chen R, Tsai CY, Plunkett W. Transcription inhibition by Actinomycin D as a mechanism-based approach to treatment of Bcr-Abl-positive chronic myelogenous leukemia. Proceedings of American Association for Cancer Research 48:764 #3211 (#3211), 2007.
9. Quintás-Cardama A, Kantarjian H, Wierda W, Ferrajoli A, Chen R, Ravandi F, Plunkett W, Cortes J. A phase II study of intravenous (iv) homoharringtonine (HHT) and imatinib (IM) in patients (pts) with chronic myeloid leukemia (CML). Blood 108(11):261, 2006.
10. Chen R, Cortes J, Gandhi V, Plunkett W. Sequential blockade of Bcr-Abl expression overcomes resistance to imatinib. National Spore Meeting, 2006.
11. Chen R, Plunkett W. Sequential blockade of Bcr-Abl production overcomes resistance to imatinib. Proceedings of the American Association for Cancer Research 47:709, 2006.
12. Chen R, Cortes J, Gandhi V, Plunkett W. A sequential blockade strategy to target the Bcr-Abl oncoprotein in chronic myelogenous leukemia with the combination of flavopiridol, homoharringtonine and Imatinib. National Spore Meeting, 2005.
13. Chen R, Keating MJ, Gandhi V, Plunkett W. Flavopiridol-induced apoptosis in chronic lymphocytic leukemia (CLL) cells through the transcriptional down-regulation of anti-apoptotic proteins. Proceedings of the American Association for Cancer Research 46:769, 2005.
14. Chen R, Plunkett W. A sequential blockade strategy to target the Bcr-Abl oncoprotein in chronic myelogenous leukemia by the combination of flavopiridol, homoharringtonine and STI571. Proceedings of the American Association for Cancer Research 45:124, 2004.
15. Pan JX, Chen R, Plunkett W. Claspin, a Chk1 interacting protein, is involved in gemcitabine-induced S phase checkpoint activation. Proceedings of the American Association for Cancer Research 45:538, 2004.
16. Chen R, Benaissa S, Plunkett W. A sequential blockade strategy to target the BCR/ABL oncoprotein in chronic myelogenous leukemia with STI571 and the protein synthesis inhibitor homoharringtonine. Proceedings of the American Association for Cancer Research 44:867, 2003.
17. Chen R, Keating MJ, Plunkett W. Transcriptional down-regulation of oncogene expression in CML and CLL by actinomycin D and flavopiridol. AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics:146 #B114, 2003.
18. Pan BF, Chen R, Farquhar D, Nelson JA. Multidrug resistance and collateral sensitivity in human renal carcinoma. Proceedings of the American Association for Cancer Research 43:951, 2002.

Grant & Contract Support

Title: Chronic Lymphocytic Leukemia Research Consortium
Funding Source: NIH/NCI
Role: Co-Investigator
Principal Investigator: Thomas Kipps
Duration: 12/1/2011 - 11/30/2016
 
Title: Investigations of the multi-kinase inhibitor TG02 in CLL
Funding Source: Tragara Pharmaceuticals, Inc.
Role: Co-Investigator
Principal Investigator: William Plunkett
Duration: 5/11/2011 - 5/31/2013
 
Title: A Phase 1 Dose-Escalation and Pharmacokinetic Study of TG02 Citrate in Patients with Advanced Hematological Malignancies
Funding Source: Tragara Pharmaceuticals, Inc.
Role: Co-Investigator
Principal Investigator: Elias Jabbour
Duration: 6/1/2010 - 6/30/2013
 
Title: Development of New Drugs for CLL
Funding Source: US-European Alliance for Chronic Lymphocytic Leukemia
Role: Co-Investigator
Principal Investigator: William Plunkett
Duration: 3/10/2008 - 12/31/2012
 
Title: A Phase I multi-center, dose-escalation clinical study of the safety and tolerability of intravenously administered SNS-032, a novel cyclin-dependent kinase inhibitor, administered to patients with advanced chronic lymphocytic leukemia.
Funding Source: Sunesis Pharmaceuticals, Inc
Role: Co-Investigator
Principal Investigator: William Wierda
Duration: 4/2007 - 1/2009
 
Title: Mechanisms of Action of SNS-032 in CLL
Funding Source: Sunesis Pharmaceuticals, Inc
Role: Co-Investigator
Principal Investigator: William Plunkett
Duration: 2/21/2007 - 2/29/2008
 
Title: Circumventing Resistance in CLL by Flavopiridol
Funding Source: Aventis
Role: Principal Investigator
Duration: 2003 - 2005

Last updated: 11/26/2012