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Ronald B. Gartenhaus, MD

Academic Title:

Professor

Primary Appointment:

Medicine

Additional Title:

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 (Primary):

(410) 328-3691

Fax:

(410) 328-6559

Education and Training

1977                B.A.    State University of New York at Albany, New York                       

1981                M.D.    Universidad del Noreste, Tampico, Mexico


Post Graduate Training

1981-1982:
Fifth Pathway Internship Long Island Jewish-Queens Hospital Center State University of New York at Stony Brook, NY

1982-1985: Internship & Residency in Internal Medicine University Hospital State University of New York at Stony Brook,NY

1985-1987: Fellowship in Medical Oncology M.D. Anderson Hospital and Tumor Institute Houston, Texas

1987-1988: IRTA Fellow National Cancer Institute (NCI), National Institutes of Health (NIH) Laboratory of Cellular and Molecular Biology Bethesda, Maryland

1988-1990: IRTA Fellow National Cancer Institute (NCI), National Institutes of Health (NIH) Laboratory of Tumor Cell Biology (LTCB)Bethesda, Maryland

1990-1992: Senior Staff Fellow, National Cancer Institute (NCI), National Institutes of Health (NIH)Laboratory of Tumor Cell Biology Bethesda, Maryland

1992: Guest Researcher National Cancer Institute (NCI), National Institutes of Health (NIH)Laboratory of Tumor Cell Biology Bethesda, Maryland

 

 

Biosketch

Ronald B. Gartenhaus, M.D. is a Tenured Professor of Medicine and Co-Leader, Program in Molecular & Structural Biology at the NCI-designated University of Maryland Marlene and Stewart Greenebaum Cancer Center. He also supervises the Hematologic Malignancies Clinic at the University affiliated Baltimore VA Hospital. Dr. Gartenhaus has a longstanding interest in lymphoma biology dating back to the early 1990's when he trained as a post-doc in the laboratory of Dr. Robert Gallo at the National Cancer Institute after completing a medical oncology fellowship at the MD Anderson Cancer Center. His laboratory was the first to identify and describe the MCT-1 oncogene. His current research focus is studying post-transcriptional/translational gene deregulation as well as oncogenic signaling cascades associated with lymphoma and how they can be exploited for targeted therapy. His research has been continually funded over the past 15 years through multiple NIH grants, VA Merit Review awards, as well as other national research foundations. Dr. Gartenhaus is a standing member of the NIH MONC study section and has participated as an ad hoc member of multiple NIH and VA reviews, including several NIH PO1 program project review panels. He has served on multiple editorial boards and is currently an Associate Editor for PLOS Genetic.

Positions and Professional Experience

1981 - 1982           Fifth-Pathway, Long Island Jewish-Queens Hospital Center, State University of New York at Stony Brook, Stony Brook, NY

1982 - 1983           Internship in Internal Medicine, University Hospital, State University of New York at Stony Brook, Stony Brook, NY

1983 - 1985           Residency in Internal Medicine, University Hospital, State University of New York at Stony Brook, Stony Brook NY

1985 - 1987           Fellowship, Medical Oncology, M.D. Anderson Hospital & Tumor Institute, Houston, TX

1987 - 1988           IRTA  Fellow,  Laboratory  of  Cellular  and  Molecular  Biology,  National  Cancer  Institute, National Institutes of Health, Bethesda, MD

1988 - 1990           IRTA Fellow, Laboratory of tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD

1990 - 1992           Senior Staff Fellow, Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD

1992                      Guest Researcher, Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD

1993 - 1996           Assistant Professor of Medicine, Albert Einstein College of Medicine, Bronx, NY

1993 - 1996           Assistant  Attending  Physician,  Division  of  Hematology/Oncology,  Long  Island  Jewish Medical Center, New Hyde Park, NY

1996 - 1999           Associate Professor and Section Chief, Molecular Oncology, MCP Hahnemann School of Medicine, Philadelphia, PA

1999 - 2004           Associate Professor of Medicine, Northwestern University Medical School

2000 - 2004           Co-Director,   Hematologic   Malignancies   Research  Program   of   the  Robert   H.   Lurie Comprehensive Cancer Center at Northwestern University

2004 - present       Associate Professor of Medicine, University of Maryland Medical School

2004 - present       Member, Program in Molecular and Structural Biology of the University of Maryland Marlene and Stewart Greenebaum Cancer Center

2007 - present       Head, Hematological Malignancies Clinic, Baltimore VA

2009 - present       Co-Leader, Program in Molecular & Structural Biology of the University of Maryland NCI-Designated Marlene and Stewart Greenebaum Comprehensive Cancer Center

2010                      Tenure awarded

2012 - present       Professor of Medicine, University of Maryland Medical School

Research/Clinical Keywords

Molecular & Structural Biology, Lymphoma biology, Post-transcriptional/translational gene deregulation, Oncogenic signaling cascades associated with lymphoma and how they can be exploited for targeted therapy

Highlighted Publications

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

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, ThomasScalea, Ferenc Livak and Ronald B. Gartenhaus. Inhibiting CARD11 translation during BCR activation by targeting the eIF4A RNA helicase. Blood. Dec 11:3758-67. 2014

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-eIF4E3 translation ‘switch’ to modulate oncogenic translation in DLBCL. Nature Communication, Nov 18; 5:5413. 2014

Bojie Dai, Raymond J. Peroutka, Simone Houng, Parameswary A Muniandy, Yongqing Zhang, Elin Lehrmann, Krystyna Mazan-Mamczarz, James Steinhardt, Ari Landon, Mikhail Shlyak, Qing Ching Chen, Kevin Becker, Rohit Talwani,Ronald B. Gartenhaus.  Hepatitis C virus up-regulates B-cell receptor signaling: a novel mechanism for HCV-associated B-cell lymphoproliferative disorders. Oncogene. Jun 9;35(23):2979-90. 2016

Bandish Kapadia, Nahid Nanaji , Kavita Bhalla , Binny Bhandary, Rena  Lapidus, Afshin Behesti, Andrew Evens and Ron Gartenhaus. FASN  induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL. Nature Communication, in press

Kavita Bhalla, Susan Jaber,Nanaji Nahid M, Karen Underwood, Afshin Beheshti, Ari Landon, Binny Bhandary, Paul Bastain, Andrew M. Evens, John Haley, Brian    Polster, and Ronald B. Gartenhaus. Selective translation of HK2 during hypoxia  promotes growth of DLBCL. Scientific Reports, 2017 in press

Research Interests

Contributions to Science

 1.    Perturbed DNA Damage Response andMicrosatellite Instability in LymphoidMalignancies. After completingmymedical oncology training at the MD Anderson Cancer Center,I began post-doctoralstudies on therole of HTLV-1 incellular transformation in the Tumor Cell Biology lab of Dr. Bob Gallo at the NCI. In 1992, I establishedmy own lab at the Long IslandJewish Medical Center,a teachingcampus at the Albert Einstein Medical College of Medicine, whereI initiatedstudies on DNA damage response andmicrosatellite instability. My labcharacterized the functional inactivation of wild-type p53 protein in HTLV-I transformed humanT lymphocytes andsubsequently, was among the first to demonstrate the induction of the p21/WAF1/CIP1 protein througha p53-independentmechanism. My group was also the first to make the original observation of amismatchrepair phenotype inasubset ofchronic lymphocytic leukemia, the first timesucha phenotype was described in a hematologicmalignancy.

 a. Gartenhaus RB, Wang P.(1995). Functional inactivation of wild-type p53 proteincorrelates with loss of IL- 2 dependence in HTLV-I transformed humanT lymphocytes. Leukemia. (12): 2082-6. PMID8609720b.   

b. Gartenhaus RB, Wang P, Hoffmann P.(1996). Induction of the WAF1/CIP1 protein and apoptosis in human T-cell leukemia virus type I-transformed lymphocytes after treatment with adriamycin by usinga p53- independent pathway. Proc Natl Acad Sci USA. 93(1): 265-8. PMID8552618c.   

c. Gartenhaus RB, Wang P, Hoffman M,Janson D, Rai K.(1996). The induction of p53 and WAF 1/CIP1 in chronic  lymphocytic  leukemia  cells  treated  with 2-chlorodeoxyadenosine.  J  Mol  Med.  (74):  143-147.  PMID8846164

d.    Gartenhaus RB,Johns MM III, Wang P, Rai, K, Sidransky D.(1996). Mutator phenotype ina subset of chronic lymphocytic leukemia.(Rapid Communication) Blood. 87: 38-41, PMID8547666

 2.    MCT-1 Oncogene. In 1998,my lab became the first and only one to successfully identify an oncogene using the arbitrarily primed-PCR(AP-PCR) assay. Specifically,my lab firstcloned and functionally characterized the oncogene MCT-1 (multiplecopies ina T-cell 1) asmodulating the expression ofasubset of mRNAs, employing polysomal profiling. We also demonstrated that MCT-1 oncoprotein is overexpressed in the vastmajority of DLBCL. Furthermore, weshowed that MEK/ERKsignaling was important for thestability and oncogenic activity of MCT-1 in DLBCL. These important findingssupported both theclinicalrelevance of potentially targeting MCT-1 and provided additional evidence linking MCT-1 with lymphoma development.

 a. Prosniak M, DierovJ, Okami K, Tilton B, Jameson B, Sawaya BE, Gartenhaus RB.(1998).A novel candidate oncogene, MCT-1, is involved incellcycle progression. Cancer Res. (Advances in Brief) 58(19): 4233-7. PMID9766643b.   

b. Shi B, Hsu HL, Evens AM, Gordon LI, GartenhausRB.(2003). Expression of thecandidate MCT-1 oncogene in B- and T-cell lymphoid malignancies. Blood. 102(1): 297-302. PMID12637315c.   

c. Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M, Bachman KE, He H, Gartenhaus RB.(2006). MCT-1 protein interacts with thecapcomplex andmodulatesmessenger RNA translational profiles. Cancer Res. 66(18): 8994-9001. PMID16982740

d.  Dai B, Zhao XF, Hagner P, Shapiro P, Mazan-Mamczarz K, Zhao S, Natkunam Y, Gartenhaus RB.(2009). Extracellularsignal-regulated kinase positivelyregulates the oncogenic activity of MCT-1 in diffuse large B-cell lymphoma. Cancer Res. 69(19): 7835-43. PMID19789340

 3.    Employingribonomicsto identifytransformation-related pathways.Ribonomics identifies and characterizes protein-RNA interactions of endogenousribonucleoprotein(RNP)complexes utilizing RIP-chip. This functional organization at the RNA level givesrise to the posttranscriptional RNA operonmodel, in which functionallyrelatedmRNAs are dynamic andcoordinatelyregulated temporally andspatially via RNP-driven mechanisms that involve RNA-binding proteins(RBPs) and target RNAs. Using this approach, we identified mRNAs fromcancer-related pathways whose association with RBPs were altered whencomparing immortalized with transformed MCF10Acells. This groundbreaking dataconvincingly demonstrated that the global alterations in binding of HuR and AUF1 with target transcripts havea keyrole in posttranscriptional regulation of genes involved in thecellular transformation process. Switching to lymphoma, we identifieda previously unidentifiedrole of ATM(Ataxia-Telangiectasia Mutated) incontrolling gene expression posttranscriptionally that is likelyrelevant to lymphoma development in afflicted ataxia-telangiectasia patients. Recently, we described how HCV infection upregulates BCRsignaling in human primaryB cells through differential association of HuR with targetmRNAs. The HCV NS3/4A proteinmodulating the CHK2 ability to phosphorylate HuRcauses these alterations. Importantly, thesestudies underscore therole of globalmRNA– protein interactions toward the development ofamoremalignant phenotype andsuggest that targeting RBP- mRNA associationsmayrepresent novel treatment strategies for humanmalignancies.

a. Mazan-Mamczarz K, Hagner PR, Wood WH, Becker KG, Gorospe M, KeeneJD, Levenson AS and Gartenhaus RB.(2008). Post-transcriptional generegulation by HuR leads toamore tumorigenic phenotype.OncogeneOct 16;27(47):6151-63. NIHMS64526

b. Mazan-Mamczarz K, Hagner PR, Wood WH, Zhang Y, Becker KG, Liu Z, Gartenhaus RB.(2008). Identification of transformation-related pathways ina breast epithelialcellmodel usingaribonomics approach. Cancer Research. (Priority Reports)68(19):7730-5. NIHMS79449

c. Mazan-Mamczarz K, Hagner PR, Zhang Y, Dai B, Wood WH, Becker KG, KeeneJD, Gorospe M, Liu Z, Gartenhaus  RB.  (2011).  ATM  regulates  a  DNA  damage  response post-transcriptional  RNA  operon in lymphocytes. Blood, Feb 24;117(8):2441-50. PMC3062410

d. Bojie Dai, RaymondJ. Peroutka, Simone Houng, ParameswaryA Muniandy, Yongqing Zhang, Elin Lehrmann, Krystyna Mazan-Mamczarz,James Steinhardt, Ari Landon, Mikhail Shlyak, Qing Ching Chen, Kevin Becker, Rohit Talwani,Ronald B. Gartenhaus(2016). HepatitisC virus up-regulates B-cellreceptor signaling:a novelmechanism for HCV-associated B-cell lymphoproliferative disorders. Oncogene.Jun 9; 35(23): 2979-90 PMID: 26434584.

4.    Targeting critical signaling pathways in Non-Hodgkin’s lymphoma. Our lab investigates actionable criticalsignaling pathwaysrelated to lymphomagenesis. Whilechronic alcohol intake has long been linked with areducedrisk of lymphoidmalignancies, there are fewmechanistic insights known. We found that ethanol specificallymodulatescap-dependent translation and global polysomal distribution profiles, and provided evidence that ethanol works to inhibit mTORsignaling ina lymphoid tissue-specificmanner. Of translational relevance, our laboratory identifiedacomplexmolecular and functional relationship between ERK and CHK2 in DLBCL. We demonstrated therapeuticsynergy when treating primary lymphomacells with both an ERK inhibitor anda CHK2 inhibitor. Recently,my lab has described how theserine/threonine kinases MNK1 and MNK2regulate an eIF4E1-eIF4E3 translation ‘switch’ tomodulate oncogenic translation in DLBCL,suggesting MNKs as novel targets in lymphoidmalignancies. Incollaboration with Dr. Evens at Tufts University, we demonstrated that the novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in DLBCL. We alsocollaborated with the Tuft’s group on defining themolecularmechanisms underlying the efficacy of the next generation proteasome inhibitor, Ixazomib in NHL.

 a. Bhalla S, Evens AM, Dai B, Prachand S, Elstrom R, Gordon LI, Gartenhaus RB.(2011). The novel anti- MEKsmallmolecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse largeB-cell lymphoma. Blood Jul 28;118(4):1052-61. PMC3148157

b. Dai B, Zhao XF, Mazan-Mamczarz K, Hagner PR, Corl S, Bahassi EM, Stambrook PJ, Shapiro  P, Gartenhaus RB. (2011). Functional andmolecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma.Nature Communication, Previewed in SciBX: Science-Business exchange,Jul 19;2:402. PMID2177227

c.  Landon A,A Muniandy P, Mazan-Mamczarz K, Houng S, Dai B, SteinhardtJ, Peroutka RJ, Borden K, and Gartenhaus RB. (2014). MNKsregulate an eIF4E1-eIF4E3 translation ‘switch’ tomodulate oncogenic translation in DLBCL.Nature Communication, Nov 18;5:5413. NIHMS632228

d.  Ravi D, Beheshti A, Abermil N, Passero F, SharmaJ, Coyle M, Kritharis A, Kandela I, Hlatky L, Sitkovsky MV, Mazar A, Gartenhaus RB, Evens AM.(2016) Anti-Proteasomal Therapy Induces MYC and CHK1 Dependent Cell Death in T-cell Lymphoma and Hodgkin Lymphoma Cells and Human Xenograft Models Cancer Res.Jun 1; 76(11): 3319-31.

5.    Posttranscriptional/Translational perturbations in lymphoma.Our group has identifiedseveral novel aspectsrelated to translational perturbations in DLBCL. My lab has described the overexpression of RpS6 in DLBCL as well as its physical association with the 5’ TOPsequence, which is important for the efficient translation ofrRNAs. We have also identified an important tumorsuppressor function ofmiR-520c-3p in regulating the eIF4G11structuralcomponent of the 4F translationcomplex. We haveshown that eIF4A- mediated enhancement of oncogene translationmay beacriticalcomponent for lymphoma progression, and specific targeting of eIF4Amay be an attractive therapeutic approach in themanagement of humanB-cell lymphomas. Finally, together with our Tuftscolleagues we have identifiedcirculatingmicroRNAspredictive of Lymphoma Development

 a. Hagner PR. Mazan-Mamczarz K, Dai B, Gartenhaus RB.(2010). Ribosomal protein S6 is highly expressed in  non-Hodgkins  lymphoma  and  associates  with  mRNA  containing  a  5’  terminal  oligopyrimidine  tract. Oncogene, Mar 31;30(13):1531-41. NIHMS337677

b. Mazan-Mamczarz K, Zhao XF, Dai B, SteinhardtJ, Berk K, Unger A, Sadowska M, Zhang Y, Lehrmann E, Becker  KG,  Shaknovich  R,  Liu Z, Gartenhaus RB.  (2014). Down-regulation of  eIF4GII bymiR-520c-3p represses diffuse largeBcell lymphoma development. PLoS Genet.Jan 30;10(1):e1004105. doi: 10.1371/journal.pgen.1004105. eCollection. PMID2449783

c. Steinhardt J, Peroutka RJ, Mazan-Mamczarz K, Chen Q, Houng S, Robles C, Barth R, DuboseJ, Bruns B, Tesoriero R, Stein D, Shakley R, Fang R, Jones K, Hanna N, PasleyJ, Rodriguez C, Kligman D, Bradley M, RabinJ, Shakleford S,A Muniandy P, Dai B, Landon AL, Scalea T, LivakF and Gartenhaus RB.(2014). Inhibiting CARD11 translation  during BCR  activation by targeting the eIF4A  RNA helicase. Blood. 124(25):3758-67. PMID25320244

d. Afshin Beheshti, Charles Vanderburg, J. Tyson McDonald, Hong Zhang, Ronald B. Gartenhaus, and Andrew M. Evens.(2017) Circulating microRNAs Predict Lymphoma Development. PLOS One, in press

Complete List of Published Work inMy Bibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/1TAPAgxjyjLAc/bibliography/47472512/public/?sort=date&direction=ascending

 

Awards and Affiliations

Honors and Awards

1987 – 1990: NIH Intramural Research Training Award

1992– 1995: Helena Rubenstein Leukemia Research Scholar

1994- 1995: National Leukemia Association Scholar

2001 – 2002: NCI Faculty Development Award

2010, 2012: Best Basic Science Publication of the Year Award, Department of Medicine,U MD School of Medicine

2014-15: Best Basic Science Publication of the Year Award, Department of Medicine,U MD School of Medicine

2015: Visiting Professor, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine

2017: Invited Scholar of the Israel Institute for Advanced Studies at The Hebrew University of Jerusalem (Sabbatical)

2017:  Visiting Professor, Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Winston Salem, NC 

Grants and Contracts

ACTIVE

P30CA134274 (Cullen) 09/01/16 – 08/31/21
NIH/NCI
University of Maryland Greenebaum Comprehensive Cancer Center Support Grant Program in Molecular and Structural Biology
Role: Co-Director
The major goals of this project are to lead and promote the interaction of investigators with common scientific interests in transcriptional and post-transcriptional gene-expression regulation

Research Award (Gartenhaus) 07/01/15 – 06/30/19 VA Merit Review
Lymphoma development in the elderly: Perturbed posttranscriptional regulation;
This project will investigate underlying mechanism(s) for the increased rate of lymphoma in our aged population by studying the function of ATM kinase, the major cellular sensor to DNA damage and downstream
targets.