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Martin Peter Carroll, MD
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Associate Professor of Medicine (Hematology-Oncology)
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Department: Medicine
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Graduate Group Affiliations
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- Immunology 6b
- Cell and Molecular Biology e
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Contact information
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Room 715, BRB II/III
32 421 Curie Blvd.
Philadelphia, PA 19104
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32 421 Curie Blvd.
Philadelphia, PA 19104
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Office: (215) 573-5217
34 Fax: (215) 573-7049
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34 Fax: (215) 573-7049
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Email:
carroll2@mail.med.upenn.edu
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carroll2@mail.med.upenn.edu
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Publications
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Links
135 Search PubMed for articles
47 Cell and Molecular Biology graduate group faculty webpage.
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135 Search PubMed for articles
47 Cell and Molecular Biology graduate group faculty webpage.
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Education:
21 9 A.B. 2c (English and American Literature) c
37 Harvard College, Cambridge, MA, 1982.
21 9 M.D. 15 (Medicine) c
3e Dartmouth Medical School, Hanover, NH, 1988.
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Permanent link21 9 A.B. 2c (English and American Literature) c
37 Harvard College, Cambridge, MA, 1982.
21 9 M.D. 15 (Medicine) c
3e Dartmouth Medical School, Hanover, NH, 1988.
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26 Molecular biology of leukemia
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4d Key words: Leukemia, BCR/ABL, signal transduction, PI3 kinase.
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26 Description of Research
537 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.
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437 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.
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20 Rotation Projects
48 1. Understanding the effects of hypoxia on growth of MDS cells.
36 2. Defining targets of mTOR signaling in AML.
36 3. Effects of BCR/ABL on genomic instability.
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1e Lab personnel:
2f Jamil Dierov PhD, DS. - Staff Scientist
31 James Thompson, M.D. - Research Associate
32 Patty Sanchez, Ph.D. - Postdoctoral Fellow
31 Xiiowei Yang, Ph.D. - Postdoctoral Fellow
25 Beth Burke - Graduate Student
2c Kristin Brennan - Research Specialist
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Description of Research Expertise
2b Research Interests26 Molecular biology of leukemia
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4d Key words: Leukemia, BCR/ABL, signal transduction, PI3 kinase.
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26 Description of Research
537 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.
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437 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.
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20 Rotation Projects
48 1. Understanding the effects of hypoxia on growth of MDS cells.
36 2. Defining targets of mTOR signaling in AML.
36 3. Effects of BCR/ABL on genomic instability.
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1e Lab personnel:
2f Jamil Dierov PhD, DS. - Staff Scientist
31 James Thompson, M.D. - Research Associate
32 Patty Sanchez, Ph.D. - Postdoctoral Fellow
31 Xiiowei Yang, Ph.D. - Postdoctoral Fellow
25 Beth Burke - Graduate Student
2c Kristin Brennan - Research Specialist
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Description of Clinical Expertise
36 Leukemia and myelodysplastic syndromes1a 29
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18e Pottier A, Park S, Lee Y, Liccardo F, Yang H, Park J, Lorant A, Schnekenburger M, Brusa D, Li V, Valente S, Mai A, Skuli SJ, Carroll M, Boettcher S, Sarry JE, Cerella C, Morceau F, Diederich M.: TP53-agnostic lethality through combined pan-HDAC and CDK inhibition in acute myeloid leukemia. Cancer Lett 633: 218011, Sep 2025.
1ac Prajapati SC, Meydan C, Neelamraju Y, Wang Z, Fan H, Dunham N, Dillon R, Gandara JA, Lee T, Sheridan C, Zumbo P, Becker MW, Bullinger L, Carroll MP, D'Andrea RJ, Levine RL, Mason C, Melnick AM, Zang C, Bekiranov S, Garrett-Bakelman FE.: CCAAT-enhancer binding protein delta functions as a tumor suppressor gene in acute myeloid leukemia. bioRxiv Aug 2025.
29f Skuli SJ, Bakayoko A, Kruidenier M, Manning B, Pammer P, Salimov A, Riley O, Brake-Sillá G, Dopkin D, Bowman M, Martinez-Gutierrez LN, Anderson CC, Reisz JA, Buono R, Paul M, Saland E, Liccardo F, DeVine A, Wong S, Xu JP, Nee E, Hausler R, Boettcher S, Sebti SM, Lai C, Maxwell KN, Sarry JE, Fruman DA, D'Alessandro A, Mesaros C, Keith B, Simon MC, Sung PJ, Wertheim G, Skuli N, Bowman RL, Matthews A, Carroll M.: Chemoresistance of TP53 mutant acute myeloid leukemia requires the mevalonate byproduct, geranylgeranyl pyrophosphate, for induction of an adaptive stress response. Leukemia Jul 2025.
221 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.: Editor's Note: Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia. Cancer Discov 15: 1297-1298, Jun 2025.
139 Senagolage MD, Blaylock HZ, Khan S, Skuli SJ, Carroll MP, McNerney ME.: NAMPT haploinsufficiency is a collateral lethal therapeutic vulnerability in high-risk myeloid malignancies with TP53 inactivation. Blood Neoplasia 2: 100119, May 2025.
13a Chow RD, Velu P, Deihimi S, Belman J, Youn A, Shah N, Luger SM, Carroll MP, Morrissette J, Bowman RL.: Persistent postremission clonal hematopoiesis shapes the relapse trajectories of acute myeloid leukemia. Blood Adv 9: 1888-1899, Apr 2025.
2be Zhang P, Whipp EC, Skuli SJ, Gharghabi M, Saygin C, Sher SA, Carroll M, Pan X, Eisenmann ED, Lai TH, Harrington BK, Chan WK, Youssef Y, Chen B, Penson A, Lewis AM, Castro CR, Fox N, Cihan A, Le Luduec JB, DeWolf S, Kauffman T, Mims AS, Canfield D, Phillips H, Williams KE, Shaffer J, Lozanski A, Doong TJ, Lozanski G, Mao C, Walker CJ, Blachly JS, Daniyan AF, Alinari L, Baiocchi RA, Yang Y, Grieselhuber NR, Campbell MJ, Baker SD, Blaser BW, Abdel-Wahab O, Lapalombella R.: TP53 mutations and TET2 deficiency cooperate to drive leukemogenesis and establish an immunosuppressive environment. J Clin Invest 135: e184021, Mar 2025.
1b5 Ayyadevara VSSA, Wertheim G, Gaur S, Chukinas JA, Loftus JP, Lee SJ, Kumar A, Swaminathan S, Bhansali RS, Childers W, Geng H, Milne TA, Hua X, Bernt KM, Besson T, Shi J, Crispino JD, Carroll M, Tasian SK, Hurtz C.: DYRK1A inhibition results in MYC and ERK activation rendering KMT2A-R acute lymphoblastic leukemia cells sensitive to BCL2 inhibition. Leukemia 2025.
19e Rowe M, Babushok D, Carroll M, Carulli A, Frey N, Gill S, Hexner E, Hirsh R, Hossain N, Lai C, Loren A, Luger S, Maillard I, McCurdy S, Matthews A, Martin ME, Paralkar VR, Perl A, Porter D, Pratz K, Stadtmauer E, Bruno XJ.: Tumor Lysis Syndrome in Acute Myeloid Leukemia Patients Treated With a Venetoclax Based Regimen. Eur J Haematol 2025.
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Selected Publications
16d Mahdavi L, Alikarami F, Goodrow H, Lenard A, Riedel SS, Libbrecht C, Bowser I, Tasian SK, Falkenstein CD, Manning B, Skuli S, Carroll MP, Wertheim G, Cai SF, McGeehan G, Yu S, Shi J, Xie HM, Bernt KM.: Upfront Menin-inhibitor resistance in multiply pretreated leukemias. Exp Hematol Sep 2025.18e Pottier A, Park S, Lee Y, Liccardo F, Yang H, Park J, Lorant A, Schnekenburger M, Brusa D, Li V, Valente S, Mai A, Skuli SJ, Carroll M, Boettcher S, Sarry JE, Cerella C, Morceau F, Diederich M.: TP53-agnostic lethality through combined pan-HDAC and CDK inhibition in acute myeloid leukemia. Cancer Lett 633: 218011, Sep 2025.
1ac Prajapati SC, Meydan C, Neelamraju Y, Wang Z, Fan H, Dunham N, Dillon R, Gandara JA, Lee T, Sheridan C, Zumbo P, Becker MW, Bullinger L, Carroll MP, D'Andrea RJ, Levine RL, Mason C, Melnick AM, Zang C, Bekiranov S, Garrett-Bakelman FE.: CCAAT-enhancer binding protein delta functions as a tumor suppressor gene in acute myeloid leukemia. bioRxiv Aug 2025.
29f Skuli SJ, Bakayoko A, Kruidenier M, Manning B, Pammer P, Salimov A, Riley O, Brake-Sillá G, Dopkin D, Bowman M, Martinez-Gutierrez LN, Anderson CC, Reisz JA, Buono R, Paul M, Saland E, Liccardo F, DeVine A, Wong S, Xu JP, Nee E, Hausler R, Boettcher S, Sebti SM, Lai C, Maxwell KN, Sarry JE, Fruman DA, D'Alessandro A, Mesaros C, Keith B, Simon MC, Sung PJ, Wertheim G, Skuli N, Bowman RL, Matthews A, Carroll M.: Chemoresistance of TP53 mutant acute myeloid leukemia requires the mevalonate byproduct, geranylgeranyl pyrophosphate, for induction of an adaptive stress response. Leukemia Jul 2025.
221 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.: Editor's Note: Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia. Cancer Discov 15: 1297-1298, Jun 2025.
139 Senagolage MD, Blaylock HZ, Khan S, Skuli SJ, Carroll MP, McNerney ME.: NAMPT haploinsufficiency is a collateral lethal therapeutic vulnerability in high-risk myeloid malignancies with TP53 inactivation. Blood Neoplasia 2: 100119, May 2025.
13a Chow RD, Velu P, Deihimi S, Belman J, Youn A, Shah N, Luger SM, Carroll MP, Morrissette J, Bowman RL.: Persistent postremission clonal hematopoiesis shapes the relapse trajectories of acute myeloid leukemia. Blood Adv 9: 1888-1899, Apr 2025.
2be Zhang P, Whipp EC, Skuli SJ, Gharghabi M, Saygin C, Sher SA, Carroll M, Pan X, Eisenmann ED, Lai TH, Harrington BK, Chan WK, Youssef Y, Chen B, Penson A, Lewis AM, Castro CR, Fox N, Cihan A, Le Luduec JB, DeWolf S, Kauffman T, Mims AS, Canfield D, Phillips H, Williams KE, Shaffer J, Lozanski A, Doong TJ, Lozanski G, Mao C, Walker CJ, Blachly JS, Daniyan AF, Alinari L, Baiocchi RA, Yang Y, Grieselhuber NR, Campbell MJ, Baker SD, Blaser BW, Abdel-Wahab O, Lapalombella R.: TP53 mutations and TET2 deficiency cooperate to drive leukemogenesis and establish an immunosuppressive environment. J Clin Invest 135: e184021, Mar 2025.
1b5 Ayyadevara VSSA, Wertheim G, Gaur S, Chukinas JA, Loftus JP, Lee SJ, Kumar A, Swaminathan S, Bhansali RS, Childers W, Geng H, Milne TA, Hua X, Bernt KM, Besson T, Shi J, Crispino JD, Carroll M, Tasian SK, Hurtz C.: DYRK1A inhibition results in MYC and ERK activation rendering KMT2A-R acute lymphoblastic leukemia cells sensitive to BCL2 inhibition. Leukemia 2025.
19e Rowe M, Babushok D, Carroll M, Carulli A, Frey N, Gill S, Hexner E, Hirsh R, Hossain N, Lai C, Loren A, Luger S, Maillard I, McCurdy S, Matthews A, Martin ME, Paralkar VR, Perl A, Porter D, Pratz K, Stadtmauer E, Bruno XJ.: Tumor Lysis Syndrome in Acute Myeloid Leukemia Patients Treated With a Venetoclax Based Regimen. Eur J Haematol 2025.
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