physician photo

Timothy P. Fleming, PhD

  • Research Professor of Surgery

Graduate School

PhD, Microbiology, University of Missouri, Columbia, 1979-1985.

Post Doctoral Education

Guest Researcher (NRSA), Laboratory of Cellular and Molecular Biology, National Cancer  Institute, Bethesda, MD, 1985-1988

Intramural Research Training Award (IRTA), Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD, 1988-1989

 

Research Interests

  • Breast cancer genetics
  • Breast cancer vaccine
  • Individualized medicine
  • EMT in cancer

Research Funding at Washington University:

KG111025 (Gillanders) 10/5/2011-10/4/2016
Susan G. Komen for the Cure
Personalized Breast Cancer Vaccines Based on Genome Sequencing

Next-generation sequencing technologies with the ability to process millions of sequence reads in a single run have revolutionized genetics, providing the ability to answer questions with unimaginable speed [69]. The vision of the Breast Cancer Research Program at WUSM is that breast cancer genome sequencing will be used in the future to tailor therapies to individual breast cancer patients, and The Genome Center is one of only a few centers worldwide with the sequencing capacity and analytical prowess to explore this vision. The flexibility of the DNA vaccine platform and the experience of investigators at WUSM provide the opportunity to rapidly translate a personalized breast cancer vaccine strategy into a phase I clinical trial.

R01 CA172623 (Aft/Watson) 9/19/2013-7/31/2018
National Institutes of Health
Analysis and Therapeutic Targeting of Breast Cancer Disseminated Tumor Cells
Our goal is to molecularly classify DTCs for predictive biomarker identification and therapeutic targeting.
 
7742-66 (Fields) 5/1/2013-4/30/2015
Barnes-Jewish Hospital Foundation
Identifying Mechanisms of Metastasis to Improve Outcomes in Metastatic Colorectal Cancer
Through a collaborative effort in Clinical Oncology, Cancer Genomics, and Computational Biology, we have organized four overlapping projects that will investigate specific aspects of metastatic tumor biology. Project 1 will perform comprehensive genomic (DNA) and transcriptomic (RNA) analysis of matched primary and mCRC tumor specimens. Project 2 will perform a comprehensive analysis of noncoding RNA in the same specimens. Project 3 will explore epigenetic differences between primary and metastatic tumor specimens. Project 4 will create and maintain xenografts and cell lines established from freshly collected primary and metastatic CRC specimens to cultivate a resource to further explore and validate pathways identified in Project 1 – 3’s investigations
 
CCR-14-500 (Gillanders) 1/1/2015-12/31/2016
Rising Tide Foundation
Phase IB Clinical Trial of a Candidate Breast Cancer Prevention Vaccine
The major goal of this project is to significantly advance the clinical development of the mammaglobin-A DNA vaccine. If an antitumor immune response is observed in the primary tumor, the trial will provide strong rationale to support initiation of a phase 2 clinical trial. If no antitumor immune response is observed in the primary tumor, the trial will provide the biologic insights required to optimize vaccine efficacy, and to support a second Phase 1b clinical trial.

7860-77 (Gillanders)
Barnes-Jewish Hospital Auxiliary
Phase IB Clinical Trial of a Candidate Breast Cancer Prevention Vaccine
The proposed trial will significantly advance the clinical development of the mammaglobin-A DNA vaccine, providing strong evidence to support initiation of a phase 2 clinical trial or providing the biologic insights required to optimize vaccine efficacy, and to support a second Phase 1b clinical trial.

BC141122 (Gillanders)
Department of Defense
Immunological Aspects of a Breast Cancer Prevention Vaccine
The goal of this project is to develop the first human breast cancer preventive vaccine through a national synergistic effort, involving several investigators. To produce such a safe and effective vaccine, we will focus on 1: Selection of vaccine antigens that are safe (do not cause autoimmunity), effective, and provide broad coverage for a diverse population of women, 2: Combine antigens into an optimal vaccine platform for preclinical studies, and 3: Conduct clinical trials to test safety and efficacy, incorporating immune monitoring and biomarkers.

(Gillanders) 1/1/2015-12/31/2016 
Rising Tide Foundation
Phase IB Clinical Trial of a Candidate Breast Cancer Prevention Vaccine
The major goal of this project is to significantly advance the clinical development of the mammaglobin-A DNA vaccine. If an antitumor immune response is observed in the primary tumor, the trial will provide strong rationale to support initiation of a phase 2 clinical trial. If no antitumor immune response is observed in the primary tumor, the trial will provide the biologic insights required to optimize vaccine efficacy, and to support a second Phase 1b clinical trial.

Selected Publications

Barbie TU, Alexe G, Aref AR, Li S, Zhu Z, Zhang X, Imamura Y, Thai TC, Huang Y, Bowden M, Herndon J,  Cohoon TJ, Fleming T, Tamayo P, Mesirov JP, Ogino S, Wong KK, Ellis MJ, Hahn WC, Barbie DA, Gillanders  WE. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth. J Clin Invest. 2014 Dec 1;124(12):5411-23. doi: 10.1172/JCI75661. Epub 2014 Nov 3.
PMID: 25365225

Tiriveedhi V, Tucker N, Herndon J, Li L, Sturmoski M, Ellis M, Ma C, Naughton M, Lockhart AC, Gao F, Fleming T, Goedegebuure P, Mohanakumar T, Gillanders WE. Safety and preliminary evidence of biologic efficacy of a  mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer. Clin Cancer Res. 2014 Dec 1;20(23):5964-75. doi: 10.1158/1078-0432.CCR-14-0059.
 PMID: 25451106

Hoekman EJ, Smit VT, Fleming TP, Louwe LA, Fleuren GJ, Hilders CG.Searching for metastases in ovarian tissue before autotransplantation: a tailor-made approach. Fertil Steril. 2015 Feb;103(2):469-77. doi:  10.1016/j.fertnstert.2014.11.001. Epub 2014 Dec 10.    PMID: 2549744

Soysal SD, Muenst S, Kan-Mitchell J, Huarte E, Zhang X, Wilkinson-Ryan I, Fleming T, Tiriveedhi V, Mohanakumar T, Li L, Herndon J, Oertli D, Goedegebuure SP, Gillanders WE. Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes.  Breast Cancer Res Treat. 2014 Oct;147(3):527-37. Epub 2014 Sep 12. PMID:  25212176

Pillai SG, Dasgupta N, Mudalagiriyappa C, Watson MA, Fleming T, Trinkaus K, Aft R. PITX2 in breast cancer invasion and recurrent disease development.  Br J Cancer.  (In Press).

Muenst S, Obermann EC, Gao F, Oertli D, Viehl CT, Weber WP, Fleming T, Gillanders WE, Soysal SD. Src homology phosphotyrosyl phosphatase-2 expression is an independent negative prognostic factor in human breast cancer.  Histopathology. 2013;63(1):74-82,

Soysal SD, Muenst S, Barbie T, Fleming T, Gao F, Spizzo G, Oertli D, Viehl CT, Obermann EC, Gillanders, WE. EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2+, basal-like, and HER2 intrinsic subtypes of breast cancer. Br J Cancer. 2013;108(7): 1480–1487.

Sankpal, NV, Fleming, TP, Gillanders WE. EpCAM modulates nuclear factor-kB signaling and interleukin-8 expression in breast cancer. Mol. Cancer Res. 2013;11:418-426.

Chidananda M. Siddappa, Mark A. Watson, Sreeraj Pillai, Kathyrn Trinkaus, Timothy Fleming, Rebecca Aft. Detection of disseminated tumor cells in the bone marrow of breast cancer patients using multiplex gene expression measurements identifies new therapeutic targets in patients at high risk for the development of metastatic disease. Breast Cancer Research and Treatment. 2013;137: 45-56.

Tiriveedhi V, Sarma NJ, Subramanian V, Fleming TP, Gillanders WE, Mohanakumar T. Identification of HLA-A24-restricted CD8+ cytotoxic T-cell epitopes derived from mammaglobin-A, a human breast cancer-associated antigen. Hum Immunol. 2012;73: 11-16.

 Li L, Kim S, Herndon JM, Goedegebuure P, Belt BA, Satpathy AT, Fleming TP, Hansen TH, Murphy KM, Gillanders WE.  Cross-dressed CD8α+/CD103+ dendritic cells prime CD8+ T cells following vaccination.
Proc Natl Acad Sci U S A. 2012;31;109(31):12716-21.

Tiriveedhi V, Fleming TP, Goedegebuure PS, Naughton M, Ma C, Lockhart C, Gao F, Gillanders WE, Mohanakumar T.  Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOS(hi) T cells. Breast Cancer Res Treat. 2013 Feb;138(1):109-18.

Li L, Goedegebuure P, Mardis ER, Ellis MJC, Zhang X, Herndon JH, Fleming TP, Carreno BM, Hansen TH, Gillanders WE. Cancer Genome Sequencing and Its Implications for Personalized Cancer.  Vaccines. 2011;3:4191-4211.

Sankpal NV, Mayfield JD, Willman MW, Fleming TP, Gillanders WE. Activator protein 1 (AP-1) contributes to EpCAM-dependent breast cancer invasion. Breast Cancer Research. 2011;13:R124.

Krumholz A, Vanvicle-Chavez SJ, Yao J, Fleming TP, Gillanders WE, Wang LV. Photoacoustic microscopy of tyrosinase reporter gene in vivo. J. Biomed Opt. 2011;16: 80-85.

Lijin L, Herndon JM, Trescott SM, Hansen TH, Fleming TP, Goedegebuure P, Gillanders W. Engineering superior DNA vaccines: MHC class I single chain trimers bypass antigen processing and enhance the immune response to low affinity antigens. Vaccine.  2010;28:1911-1918.

Li L, Herndon JM, Truscott SM, Hansen TH, Fleming TP, Goedegebuure  P, Gillanders,WE. Engineering superior DNA vaccines: MHC class I single chain trimers bypass antigen processing and enhance the immune response to low affinity antigens. Vaccine. 2010;23;28(8):1911-8.  

PubMed page for Timothy Fleming, PhD