Martin Peter Carroll
Associate Professor of Medicine
Attending Physician, Hematology Consult Service, 1 mo./yr., Hospital of the University of Pennsylvania
Attending Physician, West Philadelphia Veterans Administration Hospital
Department: Medicine
Contact information
Room 708, BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
421 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 573-5217
Fax: (215) 573-7049
Fax: (215) 573-7049
Email:
carroll2@mail.med.upenn.edu
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.
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.
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
American Board of Internal Medicine, 1991.
Medical Oncology Subspecialty Certification, 1993.
Permanent linkAmerican Board of Internal Medicine, 1991.
Medical Oncology Subspecialty Certification, 1993.
Description of Research Expertise
Research 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 Expertise
Leukemia and myelodysplastic syndromesSelected Publications
Erdogan Begum, Facey Crystal, Qualtieri Julianne, Tedesco Jason, Rinker Elizabeth, Isett R Benjamin, Tobias John, Baldwin Donald A, Thompson James E, Carroll Martin, Kim Annette S: Diagnostic microRNAs in myelodysplastic syndrome. Experimental hematology 39(9): 915-926.e2, Sep 2011.Bhattacharya Sabyasachi, Zheng Hui, Tzimas Christos, Carroll Martin, Baker Darren P, Fuchs Serge Y: Bcr-abl signals to desensitize chronic myeloid leukemia cells to interferon alpha via accelerating the degradation of its receptor. Blood Aug 2011.
Sarry Jean-Emmanuel, Murphy Kathleen, Perry Robin, Sanchez Patricia V, Secreto Anthony, Keefer Cathy, Swider Cezary R, Strzelecki Anne-Claire, Cavelier Cindy, Récher Christian, Mansat-De Mas Véronique, Delabesse Eric, Danet-Desnoyers G, Carroll Martin: Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice. The Journal of clinical investigation 121(1): 384-95, Jan 2011.
Wunderlich M, Chou F-S, Link K A, Mizukawa B, Perry R L, Carroll M, Mulloy J C: AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 24(10): 1785-8, Oct 2010.
Fernandes Margret S, Reddy Mamatha M, Croteau Nicole J, Walz Christoph, Weisbach Henry, Podar Klaus, Band Hamid, Carroll Martin, Reiter Andreas, Larson Richard A, Salgia Ravi, Griffin James D, Sattler Martin: Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism. The Journal of biological chemistry 285(42): 32596-605, Oct 2010.
Zhao F, Mancuso A, Bui T V, Tong X, Gruber J J, Swider C R, Sanchez P V, Lum J J, Sayed N, Melo J V, Perl A E, Carroll M, Tuttle S W, Thompson C B: Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1alpha-induced metabolic reprograming. Oncogene 29(20): 2962-72, May 2010.
Ward Patrick S, Patel Jay, Wise David R, Abdel-Wahab Omar, Bennett Bryson D, Coller Hilary A, Cross Justin R, Fantin Valeria R, Hedvat Cyrus V, Perl Alexander E, Rabinowitz Joshua D, Carroll Martin, Su Shinsan M, Sharp Kim A, Levine Ross L, Thompson Craig B: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer cell 17(3): 225-34, Mar 2010.
Perl Alexander E, Kasner Margaret T, Tsai Donald E, Vogl Dan T, Loren Alison W, Schuster Stephen J, Porter David L, Stadtmauer Edward A, Goldstein Steven C, Frey Noelle V, Nasta Sunita D, Hexner Elizabeth O, Dierov Jamil K, Swider Cezary R, Bagg Adam, Gewirtz Alan M, Carroll Martin, Luger Selina M: A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 15(21): 6732-9, Nov 2009.
Sanchez P V, Perry R L, Sarry J E, Perl A E, Murphy K, Swider C R, Bagg A, Choi J K, Biegel J A, Danet-Desnoyers G, Carroll M: A robust xenotransplantation model for acute myeloid leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 23(11): 2109-17, Nov 2009.
Hahn Cynthia K, Berchuck Jacob E, Ross Kenneth N, Kakoza Rose M, Clauser Karl, Schinzel Anna C, Ross Linda, Galinsky Ilene, Davis Tina N, Silver Serena J, Root David E, Stone Richard M, DeAngelo Daniel J, Carroll Martin, Hahn William C, Carr Steven A, Golub Todd R, Kung Andrew L, Stegmaier Kimberly: Proteomic and genetic approaches identify Syk as an AML target. Cancer cell 16(4): 281-94, Oct 2009.
