Ronald B. Gartenhaus, M.D. Associate Professor of Medicine
Department:
University of Maryland Greenebaum Cancer Center
UMGCC Research Program:
Molecular and Structural Biology Program
Education/Training:
College Degree:
B.A., University at Albany
Medical Degree:
M.D.
Residency:
Internal Medicine
University Hospital
State University of New York at Stony Brook
Fellowship:
Fellowship in Medical Oncology
M.D. Anderson Hospital and Tumor Institute
IRTA Fellow
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Laboratory of Tumor Cell Biology
Certification:
Diplomate, American Board of Internal Medicine
Board Certified in Medical Oncology
Contact
Information:
Mailing Address:
655 West Baltimore Street
Room 9-011, Bressler Research Building
Baltimore, Maryland 21201
Email:
rgartenhaus@som.umaryland.edu
Phone:
410-328-3691
Fax:
410-328-6559
Research Interests:
A major focus of my research program is on the molecular etiology of lymphoid malignancies. We recently cloned and identified a novel oncogene, MCT-1, found to be amplified in a human lymphoma and that appears to have a cell cycle regulatory role as well as anti-apoptotic activity. We subsequently identified a subset of primary diffuse large B-cell lymphomas (DLBCL) that exhibited significantly elevated levels of MCT-1 protein compared with normal lymphoid tissue.
The molecular mechanism(s) underlying the activity of MCT-1 are currently being investigated in the laboratory. MCT-1 has been shown to contain a PUA domain that recently has been demonstrated to mediate RNA binding activity. We found that MCT-1 is a novel cap-binding protein that enhances translation of select cancer related mRNAs through its association with DENR, a molecule containing the SUI1 domain which is involved in translation initiation. The efficiency of expression of key proteins involved in cell growth regulation, proliferation or cell death may be controlled at the translational level by changes in the activity of components of the protein synthesis machinery. With the exception of eIF4E, there are few other examples of oncogenic translation factors whose aberrant expression has been shown to induce malignant transformation of cells. We have recently established a Eu-MCT-1 transgenic mouse which will provide a useful in-vivo model to study the effects of enhanced translation of MCT-1 on lymphomagenesis. Our data provides a putative mechanism underlying the development and progression of tumors associated with dysregulation of MCT-1, and further supports the linkage between translational control and oncogenesis.
Publications:
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
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
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.
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.: MCT-1 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
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
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
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
Evens AE, Gordon LI, Prachand S, Paniaqua M, Shi B and Gartenhaus RB. Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent. Clinical Cancer Research 10:1481-91, 2004.
Shi B, Hsu HL, Evens AM, Gordon LI, and Gartenhaus RB. Expression of the candidate MCT-1 oncogene in B-and T-cell lymphoid malignancies. Blood 102:297-302, 2003
Shi B, Levenson V, and Gartenhaus RB. Identification and characterization of a novel enhancer for the human MCT-1 oncogene promoter. Journal of Cellular Biochemistry 90(1):68-79, 2003
Nasedkina TV, Zharinov VS, Isaeva EA, Yurasov R, Turigin AY, Karachunskii AI, Gartenhaus RB*, Mirzabekov AD. Clinical screening of gene rearrangements in childhood leukemia by multiplex PCR-microarray approach. Clinical Cancer Research 9(10):5620-29, 2003
Frankel AE, Fleming DR, Hall PD, Powell BL, Black JH, Leftwich C, and Gartenhaus R. A phase I study of DT fusion protein denileukin diftitox in patients with fludarabine refractory chronic lymphocytic leukemia. Clinical Cancer Research 9(10):3555-61, 2003
Herbert GB, Shi B, Gartenhaus RB. Expression and stabilization of the MCT-1 protein by DNA damaging agents. Oncogene 20:6777-6783, 2001
