About Dr. Chen
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 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 that protect plants from insect damage. Transgenic crops that express the peoteinase inhibitors will become 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 certain nucleosides are transported by specific organic cation transporters. 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 and graduate rise to assistant professor. My work focuses on developing transcription/ translation inhibitors in cancer therapy and overcoming drug resistance.
Assistant Professor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
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.
|2002||University of Texas Health Science Center, Graduate School of Biomedical Sciences, Houston, TX, USA, PHD, Cancer Biology|
|1995||Chinese Academy of Sciences, Institute of Genetics, Beijing, USA, MS, Molecular Biology|
|1992||Wuhan University, Wuhan, USA, BS, Biochemistry|
|2002-2007||Postdoctoral Fellowship, molecular pharmacology, The University of Texas MD Anderson Cancer Center, Houston, TX|
Instructor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2007 - 2010
|2013||Leukemia SPORE Career Development Award, MDACC Leukemia SPORE|
|2009||Best poster award, Gordon Research Conferences, Nucleosides, Nucleotides & Oligonucleotides|
|2006||The Kimberly Patterson Fellowship in Leukemia Research|
|2003||Aventis Translational Research Fellowship Award|
- Chen R, Zhu M, Chaudhari RR, Robles O, Chen Y, Skillern W, Qin Q, Wierda WG, Zhang S, Hull KG, Romo D, Plunkett W. Creating novel translation inhibitors to target pro-survival proteins in chronic lymphocytic leukemia. Leukemia 33(7):1663-1674, 2019. e-Pub 2019. PMID: 30700841.
- Jouanneau M, McClary B, Reyes JC, Chen R, Chen Y, Plunkett W, Cheng X, Milinichik AZ, Albone EF, Liu JO, Romo D. Derivatization of Agelastatin A Leading to Bioactive Analogs and a Trifunctional Probe. Bioorg Med Chem Lett 26(8):2092-7, 2016. e-Pub 2016. PMID: 26951751.
- Yeh YY, Chen R, Hessler J, Mahoney E, Lehman AM, Heerema NA, Grever MR, Plunkett W, Byrd JC, Johnson AJ. Up-regulation of CDK9 kinase activity and Mcl-1 stability contributes to the acquired resistance to cyclin-dependent kinase inhibitors in leukemia. Oncotarget 6(5):2667-79, 2015. PMID: 25596730.
- Koay EJ, Truty MJ, Cristini V, Thomas RM, Chen R, Chatterjee D, Kang Y, Bhosale PR, Tamm EP, Crane CH, Javle M, Katz MH, Gottumukkala VN, Rozner MA, Shen H, Lee JE, Wang H, Chen Y, Plunkett W, Abbruzzese JL, Wolff RA, Varadhachary GR, Ferrari M, Fleming JB. Transport properties of pancreatic cancer describe gemcitabine delivery and response. J Clin Invest 124(4):1525-36, 2014. e-Pub 2014. PMID: 24614108.
- 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, 2012. e-Pub 2011. PMID: 22099584.
- 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, 2012. e-Pub 2011. PMID: 21904380.
- 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, 2011. e-Pub 2011. PMID: 21632856.
- 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, 2011. e-Pub 2010. PMID: 20971952.
- 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, 2010. e-Pub 2010. PMID: 20663900.
- 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, 2010. e-Pub 2010. PMID: 20479412.
- 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, 2009. e-Pub 2009. PMID: 19762485.
- 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, 2009. e-Pub 2009. PMID: 19234140.
- 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.
- 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.
- 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 2005. PMID: 15972445.
- Chen R, Jonker JW, Nelson JA. Renal organic cation and nucleoside transport. Biochem Pharmacol 64(2):185-190, 2002. PMID: 12123738.
- Chen R, Nelson JA. Role of organic cation transporters in the renal secretion of nucleosides. Biochem Pharmacol 60(2):215-219, 2000. PMID: 10825466.
- 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, 1999. PMID: 10220855.
- 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, 1999. PMID: 9950964.
- 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.
- 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. e-Pub 1996.
- Xie Z, Chen R. Producing single cell protein from corn wastes through mixed micro-organisms culturing. Cereal & Food Industry 7:28-31, 1994.
- Chen R, Chen Y, Tsai J, Thompson PA, Burrowa FJ, Keating MJ, Wierda WG, Plunkett W. The multikinase inhibitor TG02 induces apoptosis and blocks B-cell receptor signaling in chronic lymphocytic leukemia through dual mechanisms of action. Clinical Cancer Research.
- Chen R, Plunkett W. Strategy to induce apoptosis and circumvent resistance in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol 23(1):155-66, 2010. PMID: 20620979.
- Chen R, Plunkett W. Sequential Blockade of Oncogenic Kinases. American Association for Cancer Research 96th Annual Meeting Educational Book:344-348, 2005.
- Chen R, Chen Y, Frame S, Blake D, Wierda WG, Zheleva D and Plunkett W. Strategic combination of the cyclin-dependent kinase inhibitor CYC065 with venetoclax to target anti-apoptotic proteins in chronic lymphocytic leukemia. AACR 2018 annual meeting, April 14 - 18, 2018, Chicago, Illinois, USA, 2018.
- Rong Chen, Yuling Chen, Emanuela Ghia, Laura Rassenti, Tom Kipps, Michael Keating, William Wierda and William Plunkett. Targeting SF3B1 mediated splicing control of Mcl-1 in chronic lymphocytic leukemia. Proceedings of America Association for Cancer Research 55, 2014.
- Rong Chen, Bonnie Leung, Yuling Chen and William Plunkett. Activities and Mechanism Based Combinations of Omacetaxine in Acute Myeloid Leukemia. Blood 122(21):ABs# 1288, 2013.
- 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, 2012.
- Chen R, Guo L, Chen Y, Jiang Y, Wierda W, Plunkett W. Reducing Mcl-1 by Homoharringtonine Induces Apoptosis in Chronic Lymphocytic Leukemia Cells. Blood 112, 2010.
- 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, 2010.
- 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, 2009.
- 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, 2009.
- 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, 2008.
- 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, 2008.
- 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, 2007.
- 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, 2007.
- 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.
- Chen R, Cortes J, Gandhi V, Plunkett W. Sequential blockade of Bcr-Abl expression overcomes resistance to imatinib. National Spore Meeting, 2006.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Chen R, Zhu M, Chaudhari RR, Robles O, Chen Y, Skillern W, Qin Q, Wierda W, Zhang S, Hull KG, Romo D, Plunkett W. Novel pateamine analogs to target the translation initiation factor eIF4A in chronic lymphocytic leukemia. AACR 2019 annual meeting.
|Title:||Single agent and mechanism-based combinations of CYC065 in chronic lymphocytic leukemia|
|Funding Source:||Cyclacel, Ltd|
|Title:||Strategies to target the pathophysiology of CLL|
|Funding Source:||CLL Global Research Foundation|
|Title:||CLL Moon Shot: Drug Development Project|
|Funding Source:||CLL Moon Shot|
|Title:||Chronic Lymphocytic Leukemia Research Consortium|