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Ronald B Gartenhaus

Ronald B Gartenhaus M.D.

Academic Title: Professor
Primary Appointment: Medicine
Additional Title(s): Secondary Appt: Joint Program in Biochemistry & Molecular Biology; Co-Leader, Program in Molecular & Structural Biology of the Greenebaum Cancer Center; Head, Baltimore VA Hematologic Malignancies Clinic; Member, Combined MD/PhD Committee
Location: Bressler Research Building, Room 9-011
Phone: (410) 328-3691
Fax: (410) 328-6559
Lab: (410) 328-8083

Research Interests:

I have a longstanding interest in lymphoma biology dating back to the early 1990's when I worked as a post-doc in the laboratory of Dr. Robert Gallo at the National Cancer Institute after completing my medical oncology fellowship at the MD Anderson Cancer Center. About a decade ago, my lab identified a novel oncogene, MCT-1 from a human lymphoma cell line and demonstrated its capacity to transform immortalized cells as well as to alter their cell cycle kinetics. MCT-1 interacts with the density-regulated protein (DENR/DRP), an SUI1 domain-containing domain. The SUI1 domain is involved in recognition of the initiation codon by the eIF2-GTP-Met-tRNAi ternary complex. MCT-1 contains a PsuedoUridine synthase and Archaeosine transglycosylase (PUA) domain, which is a recently described RNA binding domain. A paradigm for how MCT-1 transforms cells has been proposed in which MCT-1 bound to DENR binds to the cap complex resulting in enhanced translation initiation of cancer-related mRNAs by scanning and recognition of the initiation codon. Employing translational profiling methodology, we were able to demonstrate that MCT-1 was able to upregulate the translation of a subset of cancer-related mRNAs involved in cell growth regulation, proliferation and apoptosis.

The abnormal regulation of protein synthesis in lymphoma cells has the potential to be exploited for cancer therapy. Towards this end, we were able to show that when MCT-1 function was repressed using a dominant-negative mutant approach the translational profile of tumor cells was altered and the malignant phenotype was attenuated. Recently, we demonstrated that the vast majority of primary DLBCL (85%) have elevated protein levels of MCT-1. The current challenge is to identify the complete repertoire of translated mRNAs regulated by MCT-1. Through our ongoing collaboration with Zhenqiu Liu from the Division of Biostatistics, we hope to characterize the genetic networks and processes employing comprehensive translational profiling of DLBCL cells. These important experiments will help us to understand how perturbation of MCT-1-regulated genes contributes to lymphomagenesis.


Selected Publications

Andrew M. Evens, Philip Lecane, Sheila Prachand, Seema Singhal, Mary Paniaqua, Darren Magda, Richard Miller, *Ronald B. Gartenhaus, and Leo I. Gordon: Motexafin Gadolinium Generates Reactive Oxygen Species and Induces Apoptosis in Multiple Myeloma Cell Lines. Blood 105:1265-73, 2005 (*corresponding author)

Hsin-Ling Hsu, Bo Shi, and Ronald B. Gartenhaus: The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells. Oncogene 24(31):4956-64, 2005

Melnikov, Anatoliy A., Gartenhaus, Ronald B., Levenson, Anait S , Motchoulskaya,,Natalia A., Levenson (Chernokhvostov), Victor, V.: Multiplexed Analysis of Gene-Specific DNA Methylation. Nucleic Acids Research 33(10):e93, 2005

Ali Hachem and Ronald B. Gartenhaus. Oncogenes as Molecular Targets in Lymphoma. Blood, 106:1911-1923, 2005

Levenson A.S., Thurn T.E., Simons L.A., Osipo C., Jordan V.C., Volpert O.V ., Satcher R.L., Gartenhaus R.B.: MCT1 oncogene contributes to increased in vivo tumorigenicity of MCF7 cells through promotion of angiogenesis and inhibition of apoptosis. Cancer Research 65(23):10651-6, 2005

Line Sinnathamby, Suvobroto Nandi, Bo Shi, Helen Hui and Ronald B, Gartenhaus: MCT-1 Protein Interacts with the Cap Complex and modulates mRNA Translational Profiles. Cancer Research 66(18):8994-9001, 2006

Suvobroto Nandi, Jeanette Yu, Angelika M. Burger, Line S. Reinert and Ronald B. Gartenhaus: Expression of DNA Mismatch Repair Proteins in Transformed non-Hodgkin's Lymphoma: Relationship to Smoking. Leukemia and Lymphoma 47(9):1806-12, 2006

S Nandi, L S. Reinert, A Hachem, K Mazan-Mamczarz, P Hagner, H He and R B. Gartenhaus: Phosphorylation of MCT-1 by p42/44 MAPK is required for its stabilization in response to DNA damage. Oncogene Apr 5;26(16):2283-9, 2007

Krystyna Mazan-Mamczarz and Ronald B Gartenhaus: Translational control of the MCT-1 associated protein DENR/DRP by RNA-binding protein AUF1. Cancer Genomics & Proteomics 4: 233-240, 2007

Hsin-Ling Hsu, Chik On Choy, Jeffrey R. Sawyer, Ravi Kasiappan, Chung-Li Shu, Yi-Rong Chen, Hsin-Fen Hsu, Ronald B. Gartenhaus: MCT-1 oncogene down-regulates p53 activity and destabilizes genome structure in response to DNA damage. DNA Repair Sep 1;6(9):1319-32, 2007

Krystyna Mazan-Mamczarz, Patrick R. Hagner, Sharon Corl, William H. Wood, Kevin G. Becker, Myriam Gorospe, Jack D. Keene, Anait S. Levenson and Ronald B. Gartenhaus: Post-transcriptional gene regulation by HuR leads to a more tumorigenic phenotype. Oncogene Oct 16;27(47):6151-63, 2008

Krystyna Mazan-Mamczarz, Patrick Hagner, Bojie Dai, Sharon Corl, Zhenqui Liu and Ron B. Gartenhaus: Targeted Suppression of MCT-1 Attenuates the Malignant Phenotype Through a Translational Mechanism. Leukemia Research Mar;33(3):474-82, 2008

Krystyna Mazan-Mamczarz, Patrick R. Hagner, William H. Wood, Yongqing Zhang, Kevin G. Becker, Zhenqui Liu and Ronald B. Gartenhaus: Identification of transformation-related pathways in a breast epithelial cell model using a ribonomics approach. Cancer Research Oct 1;68(19):7730-5, 2008

Zhenqui Liu, Ronald B Gartenhaus, Ming Tan and Xiaoli Jiao: Gene and Pathway Identification with Lp Regularized Bayesian Logistic Regression. BMC Bioinformatics, Oct 3;9:412, 2008

Patrick Hagner, Krystyna Mazan-Mamczarz, Bojie Dai, Sharon Corl, Zhenqui Liu and Ronald B. Gartenhaus: Alcohol Consumption and Decreased Risk of NHL: Role of mTOR Dysfunction. Blood, May 28;113(22):5526-35, 2009

Xianfeng Frank Zhao and Ronald B. Gartenhaus. Phospho-p70S6K and cdc2/cdk1 as Therapeutic Targets for Diffuse Large B-cell Lymphoma. Expert Opinion on Therapeutic Targets, Sep;13(9):1085-93.2009

Bojie Dai, Patrick Hagner, X. Frank Zhao, Paul Shapiro, Krystyna Mazan-Mamczarz, Shuchun Zhao, Yasodha Natkunam, and Ronald B. Gartenhaus. ERK Positively Regulates the Oncogenic Activity of MCT-1 in Diffuse Large B-Cell Lymphoma. Cancer Res, October 1; 69: (19). 2009

Patrick Hagner, Abraham Schneider, and Ronald B. Gartenhaus. Targeting the Cellular Translational Machinery as a Novel Treatment Strategy for Hematologic Malignancies. Blood, March 18; 115(11): 2127 - 2135. 2010

Abraham Schneider, and Ronald B. Gartenhaus. AMPK Signaling: A Targetable Tumor Suppressor Pathway? Cancer Biology & Therapy, Dec 11;10(11). 2010

Hagner PR. Mazan-Mamczarz K, Dai B, Gartenhaus RB. Ribosomal protein S6 is highly expressed in non-Hodgkins lymphoma and associates with mRNA containing a 5’ terminal oligopyrimidine tract. Oncogene, Nov 22. [Epub ahead of print] 2010

Krystyna Mazan-Mamczarz; Patrick R Hagner; Yongqing Zhang; Bojie Dai; William HWood; Kevin G Becker; Jack D Keene; Myriam Gorospe; Zhenqui Liu; Ronald Benjamin Gartenhaus. ATM regulates a DNA damage response post-transcriptional RNA operon in lymphocytes. Blood, Feb 24;117(8):2441-50. 2011

Savita Bhalla, Andrew M. Evens, Bojie Dai, Sheila Prachand, Rebecca Elstrom, Leo I. Gordon, and Ronald B. Gartenhaus. The novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse large B-cell lymphoma. Blood May 31. [Epub ahead of print] 2011

Bojie Dai, X. Frank Zhao, Krystyna Mazan-Mamczarz, Patrick Hagner, Sharon Corl, El Mustapha Bahassi, Peter J Stambrook, Paul Shapiro and Ronald B. Gartenhaus. Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma. Nature Communication, in press