Martin Peter Carroll

faculty photo
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
Office: (215) 573-5217
Fax: (215) 573-7049
Graduate Group Affiliations
A.B. (English and American Literature)
Harvard College, Cambridge, MA, 1982.
M.D. (Medicine)
Dartmouth Medical School, Hanover, NH, 1988.
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Description of Research Expertise

Research Interests
Molecular 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

Description of Itmat Expertise

Dr. Carroll investigates hematologic diseases and is engaged in several active translational projects including signal transduction in acute myeloid leukemia, retinoid derivative for treatment of refractory AML, and pathogenesis of myelodysplastic syndromes using primary cells from patients.

Selected Publications

Nybakken G E, Canaani J, Roy D, Morrissette J D, Watt C D, Shah N P, Smith C C, Bagg A, Carroll M, Perl A E: Quizartinib elicits differential responses that correlate with karyotype and genotype of the leukemic clone. Leukemia Nov 2015.

Paguirigan Amy L, Smith Jordan, Meshinchi Soheil, Carroll Martin, Maley Carlo, Radich Jerald P: Single-cell genotyping demonstrates complex clonal diversity in acute myeloid leukemia. Science translational medicine 7(281): 281re2, Apr 2015.

Sehgal Alison R, Gimotty Phyllis A, Zhao Jianhua, Hsu Jing-Mei, Daber Robert, Morrissette Jennifer D, Luger Selina, Loren Alison W, Carroll Martin: DNMT3A Mutational Status Affects the Results of Dose-Escalated Induction Therapy in Acute Myelogenous Leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 21(7): 1614-20, Apr 2015.

Kenderian S S, Ruella M, Shestova O, Klichinsky M, Aikawa V, Morrissette J J D, Scholler J, Song D, Porter D L, Carroll M, June C H, Gill S: CD33 Specific Chimeric Antigen Receptor T Cells Exhibit Potent Preclinical Activity against Human Acute Myeloid Leukemia. Leukemia Feb 2015.

Kalota Anna, Selak Mary A, Garcia-Cid Laura A, Carroll Martin: Eltrombopag modulates reactive oxygen species and decreases acute myeloid leukemia cell survival. PloS one 10(4): e0126691, 2015.

Wertheim Gerald B W, Smith Catherine, Luskin Marlise, Rager Alison, Figueroa Maria E, Carroll Martin, Master Stephen R: Validation of DNA Methylation to Predict Outcome in Acute Myeloid Leukemia by Use of xMELP. Clinical chemistry 61(1): 249-58, Oct 2014.

Li Sheng, Garrett-Bakelman Francine, Perl Alexander E, Luger Selina M, Zhang Chao, To Bik L, Lewis Ian D, Brown Anna L, D Andrea Richard J, Ross M, Levine Ross, Carroll Martin, Melnick Ari, Mason Christopher E: Dynamic evolution of clonal epialleles revealed by methclone. Genome biology 15(9): 472, Sep 2014.

Im A P, Sehgal A R, Carroll M P, Smith B D, Tefferi A, Johnson D E, Boyiadzis M: DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies. Leukemia 28(9): 1774-83, Apr 2014.

Wertheim Gerald B W, Smith Catherine, Figueroa Maria E, Kalos Michael, Bagg Adam, Carroll Martin, Master Stephen R: Microsphere-based multiplex analysis of DNA methylation in acute myeloid leukemia. The Journal of molecular diagnostics : JMD 16(2): 207-15, Mar 2014.

Smith Catherine Choy, Lasater Elisabeth A, Lin Kimberly C, Wang Qi, McCreery Melissa Quino, Stewart Whitney K, Damon Lauren E, Perl Alexander E, Jeschke Grace R, Sugita Mayumi, Carroll Martin, Kogan Scott C, Kuriyan John, Shah Neil P: Crenolanib is a selective type I pan-FLT3 inhibitor. Proceedings of the National Academy of Sciences of the United States of America 111(14): 5319-24, Mar 2014.

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Last updated: 02/01/2016
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