Photo of Jeffrey A. Morgan,  MD

Jeffrey A. Morgan, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-6054
Fax: (617) 632-3408


jamorgan@partners.org

Jeffrey A. Morgan, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Instructor, Medicine, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Pancreas cancer is the fifth leading cause of cancer death in the United States, and arguably the most lethal of human malignancies. Of the 29,000 patients diagnosed with the disease in 1998, all but 300 are expected to die within five years of diagnosis. Efforts to develop more effective therapies have been hampered by the lack of a pancreas cancer animal model where the contribution of individual genetic lesions to the neoplastic phenotype can be explored and the sensitivity to various treatment strategies can be assessed. We are developing such a model both to facilitate preclinical trials and as an engine of gene discovery. Our initial model is theTGFa/ink4a compound mutant mouse, containing mutations in two major regulatory pathways implicated in the development of nearly all human pancreatic cancers. Preliminary observations indicate that the two mutations cooperate to generate a novel, neoplastic pancreatic ductal phenotype. This phenotype will be fully characterized, and pancreatic cell lines established from this and related compound mutants screened for novel mutations that may play a pivotal role in the development of this disease. In addition, we will use transgenic technology to facilitate the selection, propagation, and transformation in culture of highly purified populations of pancreatic duct cells, the cell type of origin of most human pancreatic cancers.

Publications

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  • Choy E, Flamand Y, Balasubramanian S, Butrynski JE, Harmon DC, George S, Cote GM, Wagner AJ, Morgan JA, Sirisawad M, Mani C, Hornicek FJ, Duan Z, Demetri GD. Phase 1 study of oral abexinostat, a histone deacetylase inhibitor, in combination with doxorubicin in patients with metastatic sarcoma. Cancer 2015; 121:1223-30. PubMed
  • Goldberg J, Fisher DE, Demetri GD, Neuberg D, Allsop S, Fonseca C, Nakazaki Y, Nemer D, Raut CP, George S, Morgan JA, Wagner AJ, Freeman GJ, Ritz J, Lezcano C, Mihm MC, Canning C, Hodi FS, Dranoff G. Biologic Activity of Autologous, Granulocyte-Macrophage Colony Stimulating Factor Secreting Alveolar Soft Parts Sarcoma and Clear Cell Sarcoma Vaccines. Clin Cancer Res 2015. PubMed
  • Serrano C, Wang Y, Mariño-Enríquez A, Lee JC, Ravegnini G, Morgan JA, Bertagnolli MM, Beadling C, Demetri GD, Corless CL, Heinrich MC, Fletcher JA. KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation. J Clin Oncol 2014. PubMed
  • George S, Feng Y, Manola J, Nucci MR, Butrynski JE, Morgan JA, Ramaiya N, Quek R, Penson RT, Wagner AJ, Harmon D, Demetri GD, Krasner C. Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors. Cancer 2014; 120:738-43. PubMed
  • Choy E, Butrynski JE, Harmon DC, Morgan JA, George S, Wagner AJ, D'Adamo D, Cote GM, Flamand Y, Benes CH, Haber DA, Baselga JM, Demetri GD. Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy. BMC Cancer 2014; 14:813. PubMed
  • Wagner AJ, Chugh R, Rosen LS, Morgan JA, George S, Gordon M, Dunbar J, Normant E, Grayzel D, Demetri GD. A phase I study of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft-tissue sarcomas. Clin Cancer Res 2013; 19:6020-9. PubMed
  • Linden PA, Morgan JA, Couper GS. Seven-year disease-free survival after radical pneumonectomy for a pulmonary artery sarcoma. J Thorac Cardiovasc Surg 2013; 146:e17-8. PubMed
  • George S, Wang Q, Heinrich MC, Corless CL, Zhu M, Butrynski JE, Morgan JA, Wagner AJ, Choy E, Tap WD, Yap JT, Van den Abbeele AD, Manola JB, Solomon SM, Fletcher JA, von Mehren M, Demetri GD. Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol 2012; 30:2401-7. PubMed
  • Quek R, Wang Q, Morgan JA, Shapiro GI, Butrynski JE, Ramaiya N, Huftalen T, Jederlinic N, Manola J, Wagner AJ, Demetri GD, George S. Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors. Clin Cancer Res 2011; 17:871-9. PubMed
  • Wagner AJ, Malinowska-Kolodziej I, Morgan JA, Qin W, Fletcher CD, Vena N, Ligon AH, Antonescu CR, Ramaiya NH, Demetri GD, Kwiatkowski DJ, Maki RG. Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 2010; 28:835-40. PubMed
  • Raut CP, Wang Q, Manola J, Morgan JA, George S, Wagner AJ, Butrynski JE, Fletcher CD, Demetri GD, Bertagnolli MM. Cytoreductive surgery in patients with metastatic gastrointestinal stromal tumor treated with sunitinib malate. Ann Surg Oncol 2010; 17:407-15. PubMed
  • Theman TA, Hartzell TL, Sinha I, Polson K, Morgan J, Demetri GD, Orgill DP, George S. Recognition of a new chemotherapeutic vesicant: trabectedin (ecteinascidin-743) extravasation with skin and soft tissue damage. J Clin Oncol 2009; 27:e198-200. PubMed
  • Raut CP, Nucci MR, Wang Q, Manola J, Bertagnolli MM, Demetri GD, Morgan JA, Muto MG, Fletcher CD, George S. Predictive value of FIGO and AJCC staging systems in patients with uterine leiomyosarcoma. Eur J Cancer 2009; 45:2818-24. PubMed
  • Demetri GD, Lo Russo P, MacPherson IR, Wang D, Morgan JA, Brunton VG, Paliwal P, Agrawal S, Voi M, Evans TR. Phase I dose-escalation and pharmacokinetic study of dasatinib in patients with advanced solid tumors. Clin Cancer Res 2009; 15:6232-40. PubMed
  • Demetri GD, Casali PG, Blay JY, von Mehren M, Morgan JA, Bertulli R, Ray-Coquard I, Cassier P, Davey M, Borghaei H, Pink D, Debiec-Rychter M, Cheung W, Bailey SM, Veronese ML, Reichardt A, Fumagalli E, Reichardt P. A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res 2009; 15:5910-6. PubMed
  • Demetri GD, Heinrich MC, Fletcher JA, Fletcher CD, Van den Abbeele AD, Corless CL, Antonescu CR, George S, Morgan JA, Chen MH, Bello CL, Huang X, Cohen DP, Baum CM, Maki RG. Molecular target modulation, imaging, and clinical evaluation of gastrointestinal stromal tumor patients treated with sunitinib malate after imatinib failure. Clin Cancer Res 2009; 15:5902-9. PubMed
  • Quek R,Morgan JA,George S,Butrynski JE,Polson K,Meyer F,Demetri GD,Block SD. Small molecule tyrosine kinase inhibitor and depression. J Clin Oncol 2008; 27:312-3. PubMed
  • Bertagnolli MM,Morgan JA,Fletcher CD,Raut CP,Dileo P,Gill RR,Demetri GD,George S. Multimodality treatment of mesenteric desmoid tumours. Eur J Cancer 2008; 44:2404-10. PubMed
  • Olawaiye AB,Morgan JA,Goodman A,Fuller AF Jr,Penson RT. Epithelioid angiosarcoma of the uterus: a review of management. Arch Gynecol Obstet 2008; 278:401-4. PubMed
  • Haining WN,Davies J,Kanzler H,Drury L,Brenn T,Evans J,Angelosanto J,Rivoli S,Russell K,George S,Sims P,Neuberg D,Li X,Kutok J,Morgan J,Wen P,Demetri G,Coffman RL,Nadler LM. CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans. Clin Cancer Res 2008; 14:5626-34. PubMed
  • Barbone D, Yang TM, Morgan JR, Gaudino G, Broaddus VC. Mammalian target of rapamycin contributes to the acquired apoptotic resistance of human mesothelioma multicellular spheroids. J Biol Chem 2008; 283:13021-30. PubMed
  • Patel TV, Morgan JA, Demetri GD, George S, Maki RG, Quigley M, Humphreys BD. A preeclampsia-like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. Journal of the National Cancer Institute 2008; 100:282-4. PubMed
  • Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, Woulfe K, Pravda E, Cassiola F, Desai J, George S, Morgan JA, Harris DM, Ismail NS, Chen JH, Schoen FJ, Van den Abbeele AD, Demetri GD, Force T, Chen MH. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007; 370:2011-9. PubMed
  • Ito H, Hornick JL, Bertagnolli MM, George S, Morgan JA, Baldini EH, Wagner AJ, Demetri GD, Raut CP. Leiomyosarcoma of the inferior vena cava: survival after aggressive management. Ann Surg Oncol 2007; 14:3534-41. PubMed
  • Desai J, Shankar S, Heinrich MC, Fletcher JA, Fletcher CD, Manola J, Morgan JA, Corless CL, George S, Tuncali K, Silverman SG, Van den Abbeele AD, van Sonnenberg E, Demetri GD. Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors. Clin Cancer Res 2007; 13:5398-405. PubMed
  • Gerin F, Baloglu O, Morgan JA, Kesari S. Central nervous system metastases from imatinib mesylate resistant gastrointestinal stromal tumor. J Neurooncol 2006; 82:227-8. PubMed
  • Raut CP, Morgan JA, Ashley SW. Current issues in gastrointestinal stromal tumors: incidence, molecular biology, and contemporary treatment of localized and advanced disease. Curr Opin Gastroenterol 2007; 23:149-58. PubMed
  • Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, Morgan JA, Dychter SS, Larsen PR, Demetri GD, Alexander EK. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 2006; 145:660-4. PubMed
  • Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, Fletcher CD, Demetri GD, Bertagnolli MM. Surgical Management of Advanced Gastrointestinal Stromal Tumors After Treatment With Targeted Systemic Therapy Using Kinase Inhibitors. J Clin Oncol 2006; 24:2325-2331. PubMed
  • Kulke MH, Kim H, Clark JW, Enzinger PC, Lynch TJ, Morgan JA, Vincitore M, Michelini A, Fuchs CS. A Phase II trial of gemcitabine for metastatic neuroendocrine tumors. Cancer 2004; 101:934-9. PubMed
  • Morgan JA, Yin Y, Borowsky AD, Kuo F, Nourmand N, Koontz JI, Reynolds C, Soreng L, Griffin CA, Graeme-Cook F, Harris NL, Weisenburger D, Pinkus GS, Fletcher JA, Sklar J. Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Cancer Res 2000; 59:6205-13. PubMed
  • Peterson JW, Kwun BD, Teramura A, Hackett JD, Morgan JA, Nishizawa S, Bun T, Zervas NT. Immunological reaction against the aging human subarachnoid erythrocyte. A model for the onset of cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg 1989; 71:718-26. PubMed
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