Martin Peter Carroll, MD

faculty photo
Associate Professor of Medicine
Attending Physician, West Philadelphia Veterans Administration Hospital
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

Liu Y, Li Q, Alikarami F, Barrett DR, Mahdavi L, Li H, Tang S, Khan TA, Michino M, Hill C, Song L, Yang L, Li Y, Pokharel SP, Stamford AW, Liverton N, Renzetti LM, Taylor S, Watt GF, Ladduwahetty T, Kargman S, Meinke PT, Foley MA, Shi J, Li H, Carroll M, Chen CW, Gardini A, Maillard I, Huggins DJ, Bernt KM, Wan L.: Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia. Cancer Discov 12: 2684-2709, Nov 2022.

Rapaport F, Seier K, Neelamraju Y, Hassane D, Baslan T, Gildea DT, Haddox S, Lee T, Murdock HM, Sheridan C, Thurmond A, Wang L, Carroll M, Cripe LD, Fernandez H, Mason CE, Paietta E, Roboz GJ, Sun Z, Tallman MS, Zhang Y, Gönen M, Levine R, Melnick AM, Kleppe M, Garrett-Bakelman FE.: Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999. Blood Cancer J 12: 137, Sep 2022.

Vergez F, Largeaud L, Bertoli S, Nicolau ML, Rieu JB, Vergnolle I, Saland E, Sarry A, Tavitian S, Huguet F, Picard M, Vial JP, Lechevalier N, Bidet A, Dumas PY, Pigneux A, Luquet I, Mansat-De Mas V, Delabesse E, Carroll M, Danet-Desnoyers G, Sarry JE, Récher C.: Phenotypically-defined stages of leukemia arrest predict main driver mutations subgroups, and outcome in acute myeloid leukemia. Blood Cancer J 12: 117, Aug 2022.

Matthews AH, Perl AE, Luger SM, Loren AW, Gill SI, Porter DL, Babushok DV, Maillard IP, Carroll MP, Frey NV, Hexner EO, Martin ME, McCurdy SR, Stadtmauer EA, Paralkar VR, Bruno XJ, Hwang WT, Margolis D, Pratz KW.: Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia. Blood Adv 6: 3997-4005, Jul 2022.

Galán-Díez M, Borot F, Ali AM, Zhao J, Gil-Iturbe E, Shan X, Luo N, Liu Y, Huang XP, Bisikirska B, Labella R, Kurland I, Roth BL, Quick M, Mukherjee S, Rabadán R, Carroll M, Raza A, Kousteni S.: Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia. Cancer Discov 12: 1106-1127, Apr 2022.

Murdock HM, Kim HT, Denlinger N, Vachhani P, Hambley BC, Manning BS, Gier S, Cho C, Tsai HK, McCurdy SR, Ho VT, Koreth J, Soiffer RJ, Ritz J, Carroll MP, Vasu S, Perales MA, Wang ES, Gondek LP, Devine SM, Alyea EP, Lindsley RC, Gibson CJ.: Impact of diagnostic genetics on remission MRD and transplantation outcomes in older AML patients. Blood 139: 3546-3557, Mar 2022.

Schaefer EJ, Wang HC, Karp HQ, Meyer CA, Cejas P, Gearhart MD, Adelman ER, Fares I, Apffel A, Lim K, Xie Y, Gibson CJ, Schenone M, Murdock HM, Wang ES, Gondek LP, Carroll MP, Vedula RS, Winer ES, Garcia JS, Stone RM, Luskin MR, Carr SA, Long HW, Bardwell VJ, Figueroa ME, Lindsley RC.: BCOR and BCORL1 Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes. Blood Cancer Discov 3: 116-135, Mar 2022.

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 81: 3604-3622, 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 138: 1465-1480, 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.

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Last updated: 11/22/2022
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