Professor Ronald DeMatteo's Biography
Personal Statement
I was appointed to the staff at Memorial Sloan-Kettering Cancer Center in 1999. Since then my research has focused on the molecular and clinical aspects of gastrointestinal stromal tumor (GIST). I have led all 3 U.S. clinical trials testing the adjuvant use of imatinib mesylate (Gleevec) following resection of localized GIST. In addition, my laboratory has studied cellular and tumor immunology. In 2008, I received a Joint Appointment in the Immunology Program of Sloan-Kettering Institute in recognition of my immunology research. I also won an institutional research award in 004. 2
Our group has made substantial contributions to the understanding of GIST and justified the use of federal funds. The current project merges my interests in the molecular aspects of GIST with immunology. Our original team included the molecular biologist who discovered the KIT gene (Peter Besmer) and an expert clinical and molecular GIST pathologist (Cristina Antonescu). I have now added the leader in the biology of CTLA-4 (James Allison) and a leader in the clinical application of anti-CTLA-4 (Jedd Wolchok). Each will serve as a consultant for the present proposal (see attached letters). Our group is uniquely positioned to carry out the proposed studies as we have a transgenic mouse model of GIST in which to study the immunologic mechanisms of imatinib therapy. Moreover, we have constant (1-2 tumors per week) access to fresh human GIST specimens from consenting patients undergoing surgery at our institution. Based on the proposed research, we hope to develop a novel clinical trial based on combining molecular therapy and immune therapy for GIST. We expect that our work will not only improve the lives of patients with GIST, but also be relevant to other cancers in which targeted molecular therapy is used.
Positions and Honors
Positions and Employment
Other Experience and Professional Memberships
1999- Member, American College of Surgeons Oncology Group (ACOSOG)
2000- Member, American Association for Cancer Research (AACR)
2000- Member, American Association for the Study of Liver Diseases (AASLD)
2000- Member, American Association of Immunologists (AAI)
2001- PI, Phase II American College of Surgeons Oncology Group (ACOSOG) intergroup trial of adjuvant imatinib in patients with resected high risk primary gastrointestinal stromal tumors (GISTs).
2002- PI, Phase III American College of Surgeons Oncology Group (ACOSOG) intergroup trial of adjuvant imatinib in patients with resected primary gastrointestinal stromal tumors (GISTs).
2002- Member, American Society of Clinical Oncology (ASCO)
2003- Member, National Comprehensive Cancer Network (NCCN) Gastrointestinal Stromal Tumor (GIST) Guidelines Committee
2005, 06 Ad hoc member, Hepatobiliary Pathophysiology Study Section (HBPP), NIH
2008- Member, National Cancer Institute (NCI) Gastrointestinal Stromal Tumor (GIST) Task Force
2009- PI, Phase II multicenter trial of extended adjuvant imatinib in patients with resected primary gastrointestinal stromal tumors (GISTs).
Honors
1986 Phi Beta Kappa Honor Society, Johns Hopkins University
1989 Alpha Omega Alpha Honor Society, Cornell University Medical College
1994-96 National Institutes of Health National Research Service Award (NRSA)
1995 Jonathan E. Rhoads Research Award, Hospital of the University of Pennsylvania
1996 British Journal of Surgery Award for Outstanding Resident, Hospital of the Univ. of Pennsylvania
1997 Leonard J. Perloff Chief Resident Teaching Award, Hospital of the University of Pennsylvania
1999 Michael Burt Memorial Award for Excellence in Fellowship, Memorial Hospital, New York
2000-02 Society for Surgery of the Alimentary Tract, Career Development Award
2004 Boyer Institutional Award for Research, Memorial Sloan-Kettering Cancer Center
2008-2010 Society of Surgical Oncology (SSO) Clinical Investigator Award (CIA)
Selected Peer-reviewed Publications (Selected from 201 peer-reviewed publications)
Most relevant to the current application
- DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JL, Brennan MF. Two hundred gastrointestinal stromal tumors - analysis of recurrence patterns and prognostic factors in survival. Ann Surg 2000; 231:51-8.
- Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D,Singer S, Brennan MF, Maki RG,DeMatteo RP. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res2005; 22:4182-90.
- DeMatteo RP, Maki RG, Singer SA, Gonen M, Brennan MF, Antonescu CR. Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg 2007; 245:347-52.
- DeMatteo RP, Gold JS, Saran L, Gonen M, Liau Kui Hin, Maki RG, Singer S, Besmer P, Brennan MF, Antonescu CR. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer 2008; 112:608-15.
- DeMatteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PWT, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; ACOSOG Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373:1097-104.
- Gold JS, Gonen M, Gutierrez A, Broto JM, Garcia del Muro X, Smyrk TC, Maki RG, Singer S, Brennan MF, Antonescu CR, Donohue JH, DeMatteo RP. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour (GIST): a retrospective analysis. Lancet Oncol 2009; 10:1045-52.
Publications on cellular immunology
- Miller G, Lahrs S, Pillarisetty V, Shah A, Xing Z, DeMatteo RP. Adenovirus infection enhances dendritic cell immunostimulatory properties and induces NK and T cell mediated tumor protection. Cancer Res 2002; 62:5260-5.
- Miller G, Pillarisetty VG, Shah AB, Lahrs S, Xing Z, DeMatteo RP. Endogenous GM-CSF overexpression in vivo results in the long-term recruitment of a distinct dendritic cell population with enhanced immunostimulatory function. J Immunol 2002; 169:2875-85.
- Chaudhry UI, Kingham TP, Plitas G, Katz SC, Raab JR, DeMatteo RP. Combined stimulation with interleukin-18 and CpG induces murine natural killer dendritic cells to produce IFN-gamma and inhibit tumor growth. Cancer Res 2006; 66:10497-504.
- Brandl K, Plitas G, Schnabl B, DeMatteo RP, Pamer EG. MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med 2007; 204:1891-900.
- Plitas G, Burt BM, Nguyen HM, Bamboat ZM, DeMatteo RP. Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis. J Exp Med 2008; 205:1277-83.
- Brandl K, Plitas G, Mihu CN, Jia T, Fleisher M, Schnabl B, DeMatteo RP, Pamer EG. Vancomycin-resistant enterococci exploit innate immune deficits induced by antibiotic treatment. Nature 2008; 455:804-7.
- Bamboat ZM, Stableford JA, Plitas G, Burt BM, Nguyen HM, Welles AP, Gonen M, Young JW, DeMatteo RP. Human liver dendritic cells promote T cell hyporesponsiveness. J Immunol 2009; 182: 1901-11.
- Burt BM, Plitas G, Zhao Z, Bamboat ZM, Nguyen HM, Dupont B, DeMatteo RP. The lytic potential of human liver NK cells is restricted by their limited expression of inhibitory killer Ig-like receptors. J Immunol 2009; 183(3):1789-96.
- Bamboat ZM, Ocuin LM, Balachandran VP, Obaid H, Plitas G, DeMatteo RP. Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion. J Clin Invest 2010; 120:559-69.
Research Support
Ongoing Research Support
2R01 DK068346 DeMatteo (PI) 7/1/10-6/31/15
Liver dendritic cells in tolerance and immunity.
The major goals are to establish the roles of toll-like receptor 9 and liver dendritic cells on liver ischemia-reperfusion injury.
Role: PI
T32 CA09501-20 Brennan (PI) 7/1/09-6/30/12
National Institutes of Health
Surgical Oncology Research Training Program.
The goal of this grant is to provide postdoctoral fellows with research training in cancer investigation.
Role: Co-investigator
Completed Research Support
R01 CA102613 DeMatteo (PI) 4/1/04-3/31/09
Molecular mechanisms in gastrointestinal stromal tumor.
The major goals are to correlate molecular and chromosomal changes of tumor specimens to clinical outcome in patients with gastrointestinal stromal tumor treated with or without adjuvant imatinib therapy
Role: PI
R01 DK068346 DeMatteo (PI) 9/1/04-8/31/09
Liver dendritic cells in tolerance and immunity.
The major goals are to investigate the immunologic function of liver plasmacytoid dendritic cells and their interaction with T cells in the induction of portal vein tolerance and immune reactivity.
Role: PI
R21 CA128391 Brown (PI) 12/1/06-11/30/08
Randomized trial of doxorubicin beads for arterial embolization of hepatocellular carcinoma.
The goals are to select the optimal method of tumor embolization and to determine how radiographic response correlates to outcome.
Role: Co-investigator
R21 AI070658 DeMatteo (PI) 7/1/06-6/30/08
Natural killer dendritic cells in Listeria infection.
The major goals are to determine the role of NK-like cells and their secretion of IFN-gamma in Listeria infection in mice.
Role: PI
