Faculty

Martin Peter Carroll, MD

faculty photo
Associate Professor of Medicine
Department: Medicine
Graduate Group Affiliations

Contact information
Room 715, BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 573-5217
Fax: (215) 573-7049
Education:
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 Clinical Expertise

Leukemia and myelodysplastic syndromes

Selected Publications

Cao Z, Budinich KA, Huang H, Ren D, Lu B, Zhang Z, Chen Q, Zhou Y, Huang YH, Alikarami F, Kingsley MC, Lenard AK, Wakabayashi A, Khandros E, Bailis W, Qi J, Carroll MP, Blobel GA, Faryabi RB, Bernt KM, Berger SL, Shi J.: ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency. Mol Cell Jul 2021.

Duault C, Kumar A, Taghi Khani A, Lee SJ, Yang L, Huang M, Hurtz C, Manning B, Ghoda LY, McDonald T, Lacayo NJ, Sakamoto KM, Carroll MP, Tasian SK, Marcucci G, Yu J, Caligiuri MA, Maecker HT, Swaminathan S.: Activated Natural Killer Cells Predict Poor Clinical Prognosis in High-risk B- and T- cell Acute Lymphoblastic Leukemia. Blood Jun 2021.

Stuani L, Sabatier M, Saland E, Cognet G, Poupin N, Bosc C, Castelli FA, Gales L, Turtoi E, Montersino C, Farge T, Boet E, Broin N, Larrue C, Baran N, Cissé MY, Conti M, Loric S, Kaoma T, Hucteau A, Zavoriti A, Sahal A, Mouchel PL, Gotanègre M, Cassan C, Fernando L, Wang F, Hosseini M, Chu-Van E, Le Cam L, Carroll M, Selak MA, Vey N, Castellano R, Fenaille F, Turtoi A, Cazals G, Bories P, Gibon Y, Nicolay B, Ronseaux S, Marszalek JR, Takahashi K, DiNardo CD, Konopleva M, Pancaldi V, Collette Y, Bellvert F, Jourdan F, Linares LK, Récher C, Portais JC, Sarry JE.: Mitochondrial metabolism supports resistance to IDH mutant inhibitors in acute myeloid leukemia. J Exp Med 218: e20200924, May 2021.

Carroll M.: Understanding how retinoic acid derivatives induce differentiation in non-M3 acute myelogeneous leukemia. Haematologica 106: 927-928, Apr 2021.

Rivera OD, Mallory MJ, Quesnel-Vallières M, Chatrikhi R, Schultz DC, Carroll M, Barash Y, Cherry S, Lynch KW.: Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia. Proc Natl Acad Sci U S A 118: e2014967118, Apr 2021.

Rapaport F, Neelamraju Y, Baslan T, Hassane D, Gruszczynska A, Robert de Massy M, Farnoud N, Haddox S, Lee T, Medina-Martinez J, Sheridan C, Thurmond A, Becker M, Bekiranov S, Carroll M, Moses Murdock H, Valk PJM, Bullinger L, D'Andrea R, Lowe SW, Neuberg D, Levine RL, Melnick A, Garrett-Bakelman FE.: Genomic and evolutionary portraits of disease relapse in acute myeloid leukemia. Leukemia Feb 2021.

Sussman RT, Manning B, Ackerman D, Bigdeli A, Pammer P, Velu PD, Luger SM, Bagg A, Carroll M, Morrissette JJD.: Interpretative differences of combined cytogenetic and molecular profiling highlights differences between MRC and ELN classifications of AML. Cancer Genet 2021.

Duy C, Li M, Teater M, Meydan C, Garrett-Bakelman FE, Lee TC, Chin CR, Durmaz C, Kawabata KC, Dhimolea E, Mitsiades CS, Doehner H, D'Andrea RJ, Becker MW, Paietta EM, Mason CE, Carroll M, Melnick AM.: Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence. Cancer Discov 2021.

Abshiru, N. A., Sikora, J. W., Camarillo, J. M., Morris, J. A., Compton, P. D., Lee, T., Neelamraju, Y., Haddox, S., Sheridan, C., Carroll, M., Cripe, L. D., Tallman, M. S., Paietta, E. M., Melnick, A. M., Thomas, P. M., Garrett-Bakelman, F. E., Kelleher, N. L.: Targeted detection and quantitation of histone modifications from 1,000 cells. PLoS One 15(10): e0240829, Oct 2020.

Fagnan, A., Bagger, F. O., Piqué-Borràs, M. R., Ignacimouttou, C., Caulier, A., Lopez, C. K., Robert, E., Uzan, B., Gelsi-Boyer, V., Aid, Z., Thirant, C., Moll, U., Tauchmann, S., Kurtovic-Kozaric, A., Maciejewski, J., Dierks, C., Spinelli, O., Salmoiraghi, S., Pabst, T., Shimoda, K., Deleuze, V., Lapillonne, H., Sweeney, C., De Mas, V., Leite, B., Kadri, Z., Malinge, S., de Botton, S., Micol, J. B., Kile, B., Carmichael, C. L., Iacobucci, I., Mullighan, C. G., Carroll, M., Valent, P., Bernard, O. A., Delabesse, E., Vyas, P., Birnbaum, D., Anguita, E., Garçon, L., Soler, E., Schwaller, J., Mercher, T.: Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease drivers. Blood 136(6): 698-714, Aug 2020.

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Last updated: 08/20/2021
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