Martin Peter Carroll
Martin Peter Carroll
421 Curie Blvd.
Philadelphia, PA 19104
Fax: (215) 573-7049
A.B. (English and American Literature)
Harvard College, Cambridge, MA, 1982.
Dartmouth Medical School, Hanover, NH, 1988.
Description of Research ExpertiseResearch 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.
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.
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 ExpertiseLeukemia and myelodysplastic syndromes
Selected PublicationsVu Ly P, Pickering Brian F, Cheng Yuanming, Zaccara Sara, Nguyen Diu, Minuesa Gerard, Chou Timothy, Chow Arthur, Saletore Yogesh, MacKay Matthew, Schulman Jessica, Famulare Christopher, Patel Minal, Klimek Virginia M, Garrett-Bakelman Francine E, Melnick Ari, Carroll Martin, Mason Christopher E, Jaffrey Samie R, Kharas Michael G: The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nature medicine Sep 2017.
Farge Thomas, Saland Estelle, de Toni Fabienne, Aroua Nesrine, Hosseini Moshen, Perry Robin, Bosc Claudie, Sugita Mayumi, Stuani Lucille, Fraisse Marine, Scotland Sarah, Larrue Clément, Boutzen Héléna, Féliu Virginie, Nicolau-Travers Marie-Laure, Cassant-Sourdy Stephanie, Broin Nicolas, David Marion, Serhan Nizar, Sarry Audrey, Tavitian Suzanne, Kaoma Tony, Vallar Laurent, Iacovoni Jason, Linares Laetitia K, Montersino Camille, Castellano Remy, Griessinger Emmanuel, Collette Yves, Duchamp Olivier, Barreira Yara, Hirsch Pierre, Palama Tony, Gales Lara, Delhommeau Francois, Garmy-Susini Barbara H, Portais Jean-Charles, Vergez Francois, Selak Mary, Danet-Desnoyers Gwenn, Carroll Martin, Récher Christian, Sarry Jean Emmanuel: Chemotherapy Resistant Human Acute Myeloid Leukemia Cells are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism. Cancer discovery 7(7): 716-735, Apr 2017.
Nabel Christopher S, DeNizio Jamie E, Carroll Martin, Kohli Rahul M: DNA Methyltransferases Demonstrate Reduced Activity against Arabinosylcytosine: Implications for Epigenetic Instability in Acute Myeloid Leukemia. Biochemistry Apr 2017.
Tasian Sarah K, Kenderian Saad S, Shen Feng, Ruella Marco, Shestova Olga, Kozlowski Miroslaw, Li Yong, Schrank-Hacker April, Morrissette Jennifer J D, Carroll Martin, June Carl H, Grupp Stephan A, Gill Saar: Optimized Depletion of Chimeric Antigen Receptor T-Cells in Murine Xenograft Models of Human Acute Myeloid Leukemia. Blood Feb 2017.
Chung Stephen S, Eng William S, Hu Wenhuo, Khalaj Mona, Garrett-Bakelman Francine E, Tavakkoli Montreh, Levine Ross L, Carroll Martin, Klimek Virginia M, Melnick Ari M, Park Christopher Y: CD99 is a therapeutic target on disease stem cells in myeloid malignancies. Science translational medicine 9(374), Jan 2017.
Wertheim Gerald B W, Luskin Marlise R, Carroll Martin, Master Stephen R: Microsphere-Based Assessment of DNA Methylation for AML Prognosis. Methods in molecular biology (Clifton, N.J.) 1633: 125-136, 2017.
Tasian S K, Hurtz C, Wertheim G B, Bailey N G, Lim M S, Harvey R C, Chen I-M, Willman C L, Astles R, Zebrowski A, Reshmi S C, Li M M, Frey N V, Luger S M, Carroll M, Perl A E: High incidence of philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) in older adults with B-ALL. Leukemia 31(4): 981-984, Dec 2016.
DiNardo Courtney D, Luskin Marlise R, Carroll Martin, Smith Catherine, Harrison Jenna, Pierce Sherry, Kornblau Steve, Konopleva Marina, Kadia Tapan, Kantarjian Hagop, Wertheim Gerald B, Master Stephen R: Validation of a Clinical Assay of Multi-Locus DNA Methylation for Prognosis of Newly Diagnosed AML. American journal of hematology 92(2): E14-E15, Nov 2016.
Tasian Sarah K, Teachey David T, Li Yong, Shen Feng, Harvey Richard C, Chen I-Ming, Ryan Theresa, Vincent Tiffaney L, Willman Cheryl L, Perl Alexander E, Hunger Stephen P, Loh Mignon L, Carroll Martin, Grupp Stephan A: Potent efficacy of combined PI3K/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood 129(2): 177-187, Oct 2016.
Luskin Marlise R, Carroll Martin, Lieberman David, Morrissette Jennifer J D, Zhao Jianhua, Crisalli Lisa, Roth David B, Luger Selina M, Porter David L, Reshef Ran: Clinical Utility of Next-Generation Sequencing for Oncogenic Mutations in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22(11): 1961-1967, Jul 2016.