James Driscoll

James J Driscoll

Assistant Professor of Medicine

Professional Summary

Professional Summary: The Driscoll Lab uses high-throughput genetic and chemical screening approaches to establish the molecular basis of human cancers. Our goal is to uncover new targets and discover more effective therapeutics for these diseases. A mainstay of the laboratory is gene and microRNA expression profiling of tumors, which provides a foundation to understand the molecular pathogenesis of these cancers and their response to therapy. We have focused on investigating novel, biologically-based therapies for hematologic malignancies and brain cancers. An ongoing interest is microRNA-based genetic screens for new therapeutic targets in multiple myeloma, leukemias and lymphomas. A recurrent theme that emerges from these unbiased approaches is that malignancies co-opt signaling pathways that are used in normal cell differentiation and activation. Therefore, we have profiled individual patients newly diagnosed with myeloma in order to tailor targeted therapy for them. It is likely that cocktails of therapeutics will be needed to overcome resistance. These essential signaling pathways provide opportunities for the development of targeted therapies for human cancers. Using this translational approach, we have identified individual microRNAs that are responsible for therapeutic resistance in multiple myeloma. These studies have been extended to early phase clinical trials to identify microRNA signatures in patients that serve as readily-available blood-borne diagnostics and as prognostics of therapeutic response. Secondly, using this approach we have identified molecular links between cancer cells and diabetes- two diseases that co-opt common intracellular signaling pathways to subvert cellular metabolism. Importantly, we have found that metformin – an inexpensive, orally-available agent used by millions worldwide for type 2 diabetes- has molecular targets similar to those currently being targeted in cancer therapy. We have found that metformin may be extremely useful for enhancing the efficacy of mechanism-based and biologically targeted drugs. Specifically, we recently found that metformin synergistically enhances the anti-cancer effect of proteasome inhibitors – the standard of care therapy for myeloma.  To summarize, our correlative gene profiling, metabolic and signaling studies in tumor cell samples from patients treated with novel agents have identified the mechanisms of sensitivity and resistance, provided the rationale for selection of patients most likely to respond, helped to design combination therapies to enhance sensitivity and overcome resistance in cancer cells and suggested ways to develop more potent, selective, and less toxic targeted therapeutics. Finally, I provide operational assistance to students, residents, fellows, faculty and staff to assist them in conducting research, writing review articles and conducting clinical trials.  We have a research team consisting of 4 laboratory members.  Funding sources include foundation grants and pharmaceutical industry contracts.
Scientific Collaborations:
We have ongoing translational and clinical collaborations with:

UC Bone Marrow Transplant team
Ronald E. Warnick, MD, Director; UC Neuroscience Institute
E. Steven Woodle, MD, Director; UC Division of Transplant Surgery
Robert Cohen, MD, UC Division of Endocrinology, Diabetes and Metabolism
Atsuo Sasaki, PhD, Division of Hematology and Oncology

 

Education

Medical Degree, St. Mary's School of Medicine 2000

Doctoral Degree, State University of New York at Buffalo 1987 (Biochemistry)

Residency, Roger Williams Medical Center 2005

Fellowship, Dana-Farber Cancer Institute 2007 (Oncology)

Research Fellow, Boston University Medical Center 1996

Research Fellow, Harvard Medical School 1993

Positions and Work Experience

07-2007 -08-2010 Post Doctoral Fellow, National Cancer Institute, Bethesda, MD

11-2005 -06-2007 Post Doctoral Fellow, Dana-Farber Cancer Institute, Boston, MA

07-2003 -06-2005 Resident, Roger Williams Medical Center, Providence, RI

07-2002 -06-2003 Intern, Roger Williams Medical Center, Providence, RI

04-2002 -06-2002 Intern, St. Joseph's Mercy Hospital, Ann Arbor, MI

07-1994 -04-1996 Research Fellow, Boston University Medical Center, Boston, MA

05-1987 -03-1993 Research Fellow, Harvard Medical School, Boston, MA

Research and Practice Interests

Proteasome-based therapies, plasma cell hematologic malignancy, Multiple Myeloma, Hematology Oncology

Research Support

Grant: #Pre-Clincial Research Agreement Investigators:Driscoll, James 11-26-2012 -11-25-2013 Bristol-Myers Squibb Co. The Role of CD28/CTLA4-CD80/CD86 Co-signaling on Plasma Cell Survival and Sensitivity to Proteasome Inhibitor-Induced Cell Death Role:PI $68,000.00 Active Level:Industry

Grant: #R56 AI139141 Investigators:Driscoll, James 08-03-2018 -07-31-2019 National Institute of Allergy and Infectious Diseases Targeting Human Plasma Cells To Overcome Humoral Responses in Transplantation Role:PI $433,081.00 Active Level:Federal

Grant: #R01 AI139141 Investigators:Driscoll, James; Tremblay, Simon; Woodle, Ervin Steve 12-17-2018 -11-30-2023 National Institute of Allergy and Infectious Diseases Targeting Human Plasma Cells To Overcome Humoral Responses in Transplantation Role:PI $173,143.00 Awarded Level:Federal

Publications

Peer Reviewed Publications

Subramani, A., Alsidawi, A., Jagannathan S., Sumita, K., Sasaki, AT, Aronow, B., Warnick, RE, Lawler, S. and Driscoll, JJ. (2013. ) Brain microenvironment-induced reduction in microRNA-768-3p promotes metastatic tumor growth, drug resistance and KRAS expression.

Driscoll, JJ, Amin, S., Le Pape, E., Lee, MJ, Trepel, J., Tannous, BA, Munshi, NC, Anderson, KC and Annunziata, CM. (2013. ) Cullin-1 controls the clinical and cellular response to bortezomib through NF-B pathway activation in myeloma .

Driscoll, JJ, Khaled, A, Jagannathan, S. and Subramani, A. (2013. ) The Mammalian Target of Rapamycin as a Therapeutic Strategy in Oncology in Mammalian Target of Rapamycin (mTOR): Structure, Signalling Pathways and Biological Effects .

Driscoll, JJ, Khaled, A, Jagannathan, S. and Subramani, A. (2013. ) Targeting the PTEN Tumor Suppressor as an Anti-Cancer Therapeutic Strategy. In PTEN: Structure, Mechanisms-of-Action, Role in Cell Signaling and Regulation .

Driscoll, JJ., De Chowdhury, R. (2012. ) Molecular Crosstalk between the proteasome, aggresomes and autophagy: Translational potential and clinical implications .Cancer Letters, , 325 ,147-154

Driscoll, J., Amin, S., Pelluru, D., Le Pape, E., Burris, J., Gootenberg, J., Li, C., Anderson, K.C., Lee, M-J., Trepel, J., Nie, M., Boddy, M.N., Munshi, N.C., and Annuniziata, C.M. (2012. ) Regulation of the clinical and cellular response to bortezomib in myeloma through he Skp1-Cullin1-Fbox E3 ubiquitin ligase complex .Blood, ,

Driscoll, J. and De Chowdhury, R. (2012. ) Targeted inhibition of the proteasome, aggresomes and autophagy as an anti-cancer strategy to enhance apoptosis and reduce drug resistance .Cancer Letters, ,

Driscoll J. and Woodle, E. Steve (2012. ) Targeting the ubiquitin+proteasome system in solid tumors, .Seminars in Hematology, ,

Driscoll J., (2011. ) The SUMOylation pathway as a potential therapeutic target in Multiple Myeloma .Multiple Myeloma, , 129

Driscoll, J., Minter, A., Driscoll, D. an Burris, J. (2011. ) The Ubiquitin+Proteasome Protein Degradation Pathway as a Therapeutic Strategy in the Treatment of Solid Tumor Malignancies .Anti-Cancer Agents in Medicinal Therapy, , Feb 11 ,242

Driscoll J., Burris, J. and Annunziata, C.M. (2011. ) Targeting the Proteasome with Bortezomib in Multiple Myeloma: Update on therapeutic benefit as an upfront single agent, induction regimen for stem cell transplantation and as maintenance therapy .American Journal Therapeutics, ,

Driscoll, J. and Rixe, O. (2010. ) In Cancer: Principles & Practice of Oncology .Advances in Oncology, , 1 ,

Driscoll, J. Pelluru, D., Lefkimmiatis, K., Fulciniti, M., Prabhala, R.H., Greipp, P., Barlogie, Tai, Y., Anderson, K.C., Annunziata C.M. and Munshi, N.C. (2010. ) The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome .Blood, , 115 ,2827

Driscoll, J., and DeChowdhury, R. (2010. ) Therapeutically Targeting the SUMOylation, Ubiquitination and Proteasome Pathways as a Novel Anticancer Strategy .Targeted Oncology, , 5 ,281

Driscoll, J., Burris, J. and Annunziata, C.M. (2010. ) Novel Strategies in the Treatment of Mutiple Myeloma: From Proteasome Inhibitors to Immunotherapy .Journal Cell Science, , 1 ,101

Driscoll, J., De Chowdhury, R., Burris, J. and Annunziata, C.M. (2010. ) The Expanding Role of Proteasome-Based Therapy in the Treatment of Hematologic Malignancies .Open Journal Hematology, , 1 ,1

Gauerke, S. and Driscoll, JJ. (2010. ) Hidradenocarcinomas: A Brief Review and Future Directions .Arch. Pathol. Lab Med., , 134 ,781-785

Driscoll, J. and Rixe, O. (2009. ) Overall Survival - Still the Gold Standard .The Cancer Journal, , 15 ,401

Driscoll, J., Brown, M., Finley, D.J. and Monaco, J.J. MHC-Linked LMP Gene Products Specifically Alter the Peptidase Activities of the Proteasome .Nature (London), , 365 ,262

Brown, M., Driscoll, J. and Monaco, J.J. MHC-Linked LMP and Proteasome Complexes are Not Identical: Implications for Divergent Function among Immunospecific Forms of the Proteasome .Journal Immunology, , 151 ,1193

Arnold, D., Driscoll, J. Androlewicz, M., Huges, El, Cresswell, P. and Spies, T. Proteasome Subunits Encoded in the MHC are Not Generally Required for the Processing of Peptides Bound by MHC Class I Molecules .Nature (London), , 360 ,171

Driscoll, J. and Finley, D.J. A Controlled Breakdown: Antigen Processing and Turnover of Viral Proteins .Cell, , 68 ,823

Brown, M., Driscoll, J. and Monaco, J.J. Structural and Seroloical Similarity of the MHC-Linked LMP and the Proteasome (Multicatalytic Protease) Complexes .Nature (London), , 353 ,355

Driscoll, JJ., Goldberg, AL. The Proteasome (Multicatalytic Protease) is a Component of the 1,500-kDa Proteolytic Complex which Degrades Ubiquitin-Conjugated Proteins .J. Biol. Chem., , 265 ,4789-4792

Driscoll, JJ, and Goldberg, AL Skeletal Muscle Proteasome can Degrade Proteins in an ATP-Dependent Process that does Not Require Ubiquitin .Proc. Natl. Acad. Sci. U.S.A., , 86 ,787-791

Potluri, Veena; Noothi, Sunil K; Vallabhapurapu, Subrahmanya D; Yoon, Sang-Oh; Driscoll, James J; Lawrie, Charles H; Vallabhapurapu, Sivakumar (2013. ) Transcriptional repression of Bim by a novel YY1-RelA complex is essential for the survival and growth of Multiple Myeloma.PloS one, , 8 (7 ) ,e66121

Kim, Kui-Jin; Godarova, Alzbeta; Seedle, Kari; Kim, Min-Ho; Ince, Tan A; Wells, Susanne I; Driscoll, James J; Godar, Samuel (2013. ) Rb Suppresses Collective Invasion, Circulation and Metastasis of Breast Cancer Cells in CD44-Dependent Manner.PloS one, , 8 (12 ) ,e80590

Subramani, Arasukumar; Alsidawi, Samer; Jagannathan, Sajjeev; Sumita, Kazutaka; Sasaki, Atsuo T; Aronow, Bruce; Warnick, Ronald E; Lawler, Sean; Driscoll, James J (2013. ) The brain microenvironment negatively regulates miRNA-768-3p to promote K-ras expression and lung cancer metastasis.Scientific reports, , 3 ,2392

Driscoll, James J; Chowdhury, Roopa De (2012. ) Molecular crosstalk between the proteasome, aggresomes and autophagy: translational potential and clinical implications.Cancer letters, , 325 (2 ) ,147-54

Driscoll, James J; Woodle, E Steve (2012. ) Targeting the ubiquitin+proteasome system in solid tumors.Seminars in hematology, , 49 (3 ) ,277-83

Ahmad, N; Haider, S; Jagannathan, S; Anaissie, E; Driscoll, J J (2014. ) MicroRNA theragnostics for the clinical management of multiple myeloma.Leukemia, , 28 (4 ) ,732-8

Haider, Sajjad; Ahmad, Nisar; Anaissie, Elias; Driscoll, James J (2014. ) Future directions in the clinical management of amyloid light-chain amyloidosis.Leukemia & lymphoma, ,

Keywords

Proteasome, Metabolism, MicroRNAs, Hematologic Malignancies, Brain Malignancies, Developmental Therapeutics

Contact Information

Academic - Vontz Center for Molecular Studies
3125 Eden Avenue, Room 2302
Cincinnati  Ohio, 45267
Phone: 513-558-2186
Fax: 513-558-6703
james.driscoll@uc.edu