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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
rgartenhaus@som.umaryland.edu
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.


Publications:

Selected Publications

Patrick Hagner, Abraham Schneider, and Ronald B. Gartenhaus. Targeting the translational machinery as a novel treatment strategy for hematologic malignancies. Blood, March18; 115(11): 2127 - 2135. 2010

Zhou, Hua; Mazan-Mamczarz, Krystyna; Martindale, Jennifer; Barker, Andrew; Liu, Zhenqiu; Gorospe, Myriam; Leedman, Peter J.; Gartenhaus, Ronald; Hamburger, Anne; Zhang, Yuexing. Posttranscriptional regulation of androgen receptor mRNA by an ErbB3 binding protein 1 (EBP1) in prostate cancer. Nucleic Acids Research Jun 1;38(11):3619-31. 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, 30, 1531–1541. 2011

Zhenqiu Liu Dechang Chen Ming Tan Feng Jiang and Ronald B Gartenhaus. Kernel based methods for accelerated failure time model with ultra-high dimensional data. BMC Bioinformatics, Dec 21;11(1):606. 2010

Krystyna Mazan-Mamczarz; Patrick R Hagner; Yongqing Zhang; Bojie Dai; William H Wood; Kevin G Becker; Jack D Keene; Myriam Gorospe; Zhenqui Liu; Ronald 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 Jul 28;118(4):1052-61. 2011

Bojie Dai, X. Frank Zhao, Krystyna Mazan-Mamczarz, Patrick Hagner, Sharon Corl, El Mustapha Bahassi, Song Lu, 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, Previewed in SciBX: Science-Business exchange, Jul 19;2:402. 2011

James J. Steinhardt and Ronald B. Gartenhaus. Personalizing therapeutic options for diffuse large B-cell lymphoma subtypes with oncogene addictions. Clinical Cancer Research, Sep 1;18(17):4538-48. 2012

James J. Steinhardt and Ronald B. Gartenhaus. Epigenetic approaches for chemo-sensitization of refractory diffuse large B-cell lymphomas. Cancer Discovery, Sep; 3(9):968-70. 2013

Krystyna Mazan-Mamczarz and Ronald B. Gartenhaus. Role of microRNA Deregulation in the Pathogenesis of Diffuse Large B-cell Lymphoma. Leukemia Research, Nov;37(11):1420-8. 2013

Krystyna Mazan-Mamczarz, Frank Zhao, Bojie Dai, James Steinhardt, Kimberly Berk, Ari Unger, Mariola Sadowska, Yonqing Zhang, Elin Lehrmann, Kevin Becker, Rita Shaknovich, Zhenqiu Liu, Ronald B. Gartenhaus. Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. PLoS Genet 10(1): e1004105. doi:10.1371. 2014

Cairo Cristiana, Naveen Surendran, Mazan-Mamczarz Krystyna, Sakoda Yukimi, Diaz-Mendez Felisa, Tamada Koji, Gartenhaus Ronald, Mann Dean, Pauza David. Vγ2Vδ2 T cell Costimulation Increases NK cell Killing of Monocyte-derived Dendritic Cells. Immunology, 2014 Sep 16. [Epub ahead of print]

James J. Steinhardt, Raymond J. Peroutka, Krystyna Mazan-Mamczarz, Qing Chen, Simone Houng, Carol Robles, Rolf Barth, Joseph Dubose, Brandon Bruns, Ronald Tesoriero, Deborah Stein, Ryan Shakley, Raymond Fang, Kevin Jones, Nader Hanna, Jason Pasley, Carlos Rodriguez, David Kligman, Matthew Bradley, Joseph Rabin, Stacey Shakleford, Bojie Dai, Ari L. Landon, Thomas Scalea, Ferenc Livak and Ronald B. Gartenhaus. Inhibiting CARD11 translation during BCR activation by targeting the eIF4A RNA helicase. Blood, 2014 Oct 15. [Epub ahead of print]

Dashnamoorthy Ravi, Savita Bhalla, Ronald B Gartenhaus, Jennifer Crombie, Irawati Kandela, Jaya Sharma, Andrew Mazar, Andrew M. Evens. The Novel Organic Arsenical Darinaparsin Induces MAPK-Mediated and SHP1 Dependent Cell Death in T-cell Lymphoma and Hodgkin Lymphoma Cells and Human Xenograft Models. Clinical Cancer Research, 2014 Oct 14. [Epub ahead of print]

Ari Landon, Parameswary A. Muniundy, Krystyna Mazan-Mamczarz, Simone Houng, Bojie Dai, James Steinhardt, RJ Peroutka, Katherine Borden and Ronald B. Gartenhaus. MNKs regulate an eIF4E1-eIF4E3translation ‘switch’ to modulate oncogenic translation in DLBCL. Nature Communication, in press