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Martin Peter CarrollAssociate Professor of Medicine
Department: Medicine
Contact information
Room 708, BRB II/III
421 Curie Blvd. Philadelphia, PA 19104
Office: (215) 573-5217
Fax: (215) 573-7049 Email: carroll2@mail.med.upenn.edu
Graduate Group Affiliations
Publications
Education:
A.B. (English and American Literature) Harvard College, Cambridge, MA, 1982. M.D. (Medicine) Dartmouth Medical School, Hanover, NH, 1988.
Post-Graduate Training
Intern in Medicine , Columbia-Presbyterian Medical Center, New York, 1988-1989. Resident in Medicine , Columbia-Presbyterian Medical Center, New York, 1990-1991. Clinical Fellowship, Hematology and Oncology , Beth Israel Hospital, Boston, 1991-1992. Research Fellow, Laboratory of Dr. Alan D'Andrea, Dana-Farber , Cancer Institute, Boston, MA, 1992-1995. Research Fellow, Laboratory of Dr. D. Gary Gilliland, , Brigham and Women's Hospital, Boston, MA, 1995-1998.
Certifications
Permanent linkAmerican Board of Internal Medicine, 1991. Medical Oncology Subspecialty Certification, 1993. Description of Research ExpertiseResearch InterestsMolecular biology of leukemia Key words: Leukemia, BCR/ABL, signal transduction, PI3 kinase. Description of Research My laboratory is broadly interested in the molecular biology of leukemia. There are two active areas of research in the laboratory. The first project focused on acute myeloid leukemia (AML). AML has been hypothesized to arise from a combination of oncogenic translocations that disrupt cellular disruption and dysregulation of cellular growth regulatory mechanisms. Although a number of translocations are identified which block differentiation in AML cells, the mechanism of increased cell growth is poorly understood. We are working to understand the signal transduction pathways activated in primary cells from patients with acute myeloid leukemia (AML). We have recently found that over 80% of AML patient samples have activation of the PI3 kinase signaling pathway and that these cells require activation of the PI3 kinase pathway for survival. We are continuing to work on the PI3 kinase pathway in these primary patient cells in order to determine the exact role of the pathway in AML. Experiments are in progress to test the use of PI3 kinase pathway inhibitors in the therapy of AML using a NOD/SCID xenograft model of the disease. We are also working to develop improved culture conditions for primary AML cells in order to define the growth regulatory pathways that maintain the survival of these cells in patients. A second project involves the role of genomic instability in progression of chronic myeloid leukemia (CML) from the chronic phase to the terminal blast crisis phase of disease. CML arises because of the t(9;22) translocation which gives rise to the BCR/ABL oncogene. Extensive work has shown that BCR/ABL is a constitutively activated tyrosine kinase that leads to constitutive activation of signal transduction pathways in leukemic cells causing their aberrant growth. However, the role of BCR/ABL in progression to blast crisis is unknown. We have recently demonstrated that BCR/ABL alters the cellular response to DNA damage. After DNA damage, BCR/ABL translocates from the cytoplasm to the nucleus. In the nucleus, the oncogene associates with and disrupts the function of the ataxia-telangiectasia and rad 3 related (ATR) protein which regulates cell cycle checkpoints and DNA repair. We are actively working on trying to define the mechanism of translocation and association with ATR in order to better understand the role of BCR/ABL in progression of this disease. Rotation Projects for 2006-2007 1. Understanding the effects of hypoxia on growth of MDS cells. 2. Defining targets of mTOR signaling in AML. 3. Effects of BCR/ABL on genomic instability. Lab personnel: Jamil Dierov PhD, DS. - Staff Scientist James Thompson, M.D. - Research Associate Patty Sanchez, Ph.D. - Postdoctoral Fellow Xiiowei Yang, Ph.D. - Postdoctoral Fellow Beth Burke - Graduate Student Kristin Brennan - Research Specialist Description of Clinical ExpertiseLeukemia and myelodysplastic syndromesSelected PublicationsDierov J, Dierova R, Carroll, M : BCR/ABL Translocates to the Nucleus and Disrupts an ATR Dependent Intra-S phase Checkpoint, submitted. Cancer Cell 5: 275, 2004.Salto-Tellez S, Shelat SG, Benoit B, Rennert H, Carroll M, Leonard GB, Nowell P and Bagg A: Multiplex RT-PCR for the detection of leukemia-associated translocations: test validation and application to routine molecular diagnostic practice, submitted. The Journal of Molecular Diagnostics 5(4): 231, 2003. Xu, Q.,Simpson S., Carroll M.: PI3 Kinase Dependent Pathways in the Grwoth and Survival of AML Blasts. Blood 102(3): 972, 2003. Dierov J, Dierova R, Xu Q, Carroll M. : TEL/PDGFƒÒR Activates PI3 Kinase and Requires PI3 kinase for Regulation of the G1 to S phase Transition. Blood 99(5): 1758, 2002. Carroll M.: Beyond Directed Therapeutics: Are two drugs always better than One? Cancer Biology and Therapy 1(6): 683, 2002. Sternberg DW, Carroll M, Barker G, Palmer AM, Kazlauskas A, Gilliland DW. : The TEL/PDGFƒÒR Fusion in Chronic Myelomonocytic Leukemia Does Not Require the Known SH2 Interaction Sites for Transformation Blood 98(12): 3390, 2001. Carroll M, Palmer AM, Mahajan S, Frank D, Gilliland DG.: The TEL/PDGFƒÒR Fusion Protein activates STAT 1 and 5: A Common Mechanism of Transformation by Tyrosine Kinase Fusion Proteins. Experimental Hematology May 28(5 ): 584, May 2000. Dierov J, Daley GQ and Carroll M.: BCR/ABL Alters the Kinetics of DNA Repair in Transformed Cells After DNA Double Strand Damage. Blood 96(11), 2000.
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