Martin Peter Carroll
Associate Professor of Medicine
Department: Medicine
Graduate Group Affiliations
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
Publications
Education:
A.B. (English and American Literature)
Harvard College, Cambridge, MA, 1982.
M.D. (Medicine)
Dartmouth Medical School, Hanover, NH, 1988.
Permanent linkA.B. (English and American Literature)
Harvard College, Cambridge, MA, 1982.
M.D. (Medicine)
Dartmouth Medical School, Hanover, NH, 1988.
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
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
Selected Publications
Dinardo Courtney D, Propert Kathleen J, Loren Alison W, Paietta Elisabeth, Sun Zhuoxin, Levine Ross L, Straley Kimberly S, Yen Katharine, Patel Jay P, Agresta Samuel, Abdel-Wahab Omar, Perl Alexander E, Litzow Mark R, Rowe Jacob M, Lazarus Hillard M, Fernandez Hugo F, Margolis David J, Tallman Martin S, Luger Selina M, Carroll Martin: Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia. Blood May 2013.TCGA: Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. The New England journal of medicine 368(22): 2059-74, May 2013.
Diab Adi, Zickl Lynette, Abdel-Wahab Omar, Jhanwar Suresh, Gulam Manjit A, Panageas Katherine S, Patel Jay P, Jurcic Joseph, Maslak Peter, Paietta Elisabeth, Mangan James K, Carroll Martin, Fernandez Hugo F, Teruya-Feldstein Julie, Luger Selina M, Douer Dan, Litzow Mark R, Lazarus Hillard M, Rowe Jacob M, Levine Ross L, Tallman Martin S: Acute myeloid leukemia with translocation t(8;16) presents with features which mimic acute promyelocytic leukemia and is associated with poor prognosis. Leukemia research 37(1): 32-6, Jan 2013.
Sugita M, Kalota A, Gewirtz A M, Carroll M: Eltrombopag inhibition of acute myeloid leukemia cell survival does not depend on c-Mpl expression. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 27(5): 1207-10, Nov 2012.
Abdel-Wahab Omar, Adli Mazhar, Lafave Lindsay M, Gao Jie, Hricik Todd, Shih Alan H, Pandey Suveg, Patel Jay P, Chung Young Rock, Koche Richard, Perna Fabiana, Zhao Xinyang, Taylor Jordan E, Park Christopher Y, Carroll Martin, Melnick Ari, Nimer Stephen D, Jaffe Jacob D, Aifantis Iannis, Bernstein Bradley E, Levine Ross L: ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression. Cancer Cell 22(2): 180-93, Aug 2012.
Lee D W, Futami M, Carroll M, Feng Y, Wang Z, Fernandez M, Whichard Z, Chen Y, Kornblau S, Shpall E J, Bueso-Ramos C E, Corey S J: Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155. Oncogene 31(37): 4085-94, Jan 2012.
Hexner EH, Hoffman R, Roboz G, Luger S, Mascarenhas J, Carroll M, Clement R, Bensen-Kennedy D, and Moliterno A: An open-label study of oral CEP-701 in patients with polycythemia vera or essential thrombocythemia with the JAK2 V617F mutation. Blood 2012 Notes: Submitted.
Perl Alexander E, Kasner Margaret T, Shank Doris, Luger Selina M, Carroll Martin: Single-cell Pharmacodynamic Monitoring of S6 Ribosomal Protein Phosphorylation in AML Blasts During a Clinical Trial Combining the mTOR Inhibitor Sirolimus and Intensive Chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 18(6): 1716-25, Dec 2011.
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 118(15): 4179-87, Aug 2011.