Faculty

Martin Peter Carroll, MD

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

Email:
carroll2@mail.med.upenn.edu

Publications

Search PubMed for articles

Education:
A.B. (English and American Literature)
Harvard College, Cambridge, MA, 1982.
M.D. (Medicine)
Dartmouth Medical School, Hanover, NH, 1988.

Links
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.

Permanent link

> Perelman School of Medicine > Faculty > Details

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

Sabatier M, Birsen R, Lauture L, Mouche S, Angelino P, Dehairs J, Goupille L, Boussaid I, Heiblig M, Boet E, Sahal A, Saland E, Santos JC, Armengol M, Fernandez-Serrano M, Farge T, Cognet G, Simonetta F, Pignon C, Graffeuil A, Mazzotti C, Avet-Loiseau H, Delos O, Bertrand-Michel J, Chedru A, Dembitz V, Gallipoli P, Anstee NS, Loo S, Wei AH, Carroll M, Goubard A, Castellano R, Collette Y, Vergez F, Mansat-De Mas V, Bertoli S, Tavitian S, Picard M, Recher C, Bourges-Abella N, Granat F, Kosmider O, Sujobert P, Colsch B, Joffre C, Stuani L, Swinnen JV, Guillou H, Roue G, Hakim N, Dejean AS, Tsantoulis P, Larrue C, Bouscary D, Tamburini J, Sarry JE.: C/EBPa confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia. Cancer Discov Apr 2023.

Kumar A, Taghi Khani A, Duault C, Aramburo S, Sanchez Ortiz A, Lee SJ, Chan A, McDonald T, Huang M, Lacayo NJ, Sakamoto KM, Yu J, Hurtz C, Carroll M, Tasian SK, Ghoda L, Marcucci G, Gu Z, Rosen ST, Armenian S, Izraeli S, Chen CW, Caligiuri MA, Forman SJ, Maecker HT, Swaminathan S.: Intrinsic suppression of type I interferon production underlies the therapeutic efficacy of IL-15-producing natural killer cells in B-cell acute lymphoblastic leukemia. J Immunother Cancer 2023.

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.

Matthews AH, Pratz KW, Carroll MP.: Targeting Menin and CD47 to Address Unmet Needs in Acute Myeloid Leukemia. Cancers (Basel) 14: 5906, 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.