Vice Chair Translational Medicine, SWOG, Portland, OR
Professor of Surgery, Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
The overall goal of our laboratory is to investigate mechanisms of tumor growth, metastasis, and resistance to therapies, in gastrointestinal (GI) malignancies with a focus on colorectal cancer.
For over 2 decades, our laboratory has investigated the role of VEGF in tumor growth, metastasis and angiogenesis. We have recently focused our efforts on determining the role of VEGF signaling on and in tumor cells. Investigations in these areas may help elucidate mechanisms of action of anti-VEGF therapy, and help develop new therapeutic approaches. A major focus of the laboratory is to elucidate the complex cross-talk of endothelial cells and tumors cells, and how this influences chemoresistance in the tumor microenvironment. We recently showed that endothelial cells secrete angiocrine factors the mediate the stem-ness of nearby colon cancer cells (Cancer Cell 2013).
Continuing along our translational themes, we are studying mechanisms of resistance to standard chemotherapy for colon cancer. We have established a series of chemotherapy resistant colon cancer lines. Initial investigations demonstrated that oxaliplatin resistant colon cancer cells led to epithelial to mesenchymal transition (EMT) and the cancer stem cell phenotype. Although targeted therapies for GI malignancies has demonstrated promise in clinical trials, we strongly believe that it is important to validate new targets for the next generation of anti-neoplastic regimens. Continuing along our translational themes, we are studying mechanisms of resistance to standard chemotherapy for colon cancer. We have established chemotherapy resistant colon cancer and gastric cancer cell lines. Initial investigations demonstrated that oxaliplatin resistant colon cancer cells led to epithelial to mesenchymal transition (EMT) and the cancer stem cell phenotype. We are now collaborating with John Zhang, adjunct appointment, Department of Cancer Biology, to understand metabolic alterations that occur in chemoresistant cell lines. Similarly, with the input of George Calin, we are studying miRNA alterations in chemoresistant cell lines. Although targeted therapies for GI malignancies has demonstrated promise in clinical trials, we strongly believe that it is important to validate new targets for the next generation of anti-neoplastic regimens.
|1983||University of Virginia, Charlottesville, VA, USA, MD, Medicine|
|1990-1992||Surgical Oncology Fellow, Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX|
|1986-1988||Post-Doctoral Fellow, University of Florida, Gainesville, FL|
|1991||American Board of Surgery|
|2007||William C. Liedtke Jr. Chair in Cancer Research, U.T. M. D. Anderson Cancer Center|
- Lu J, Ye X, Fan F, Xia L, Bhattacharya R, Bellister S, Tozzi F, Sceusi E, Zhou Y, Tachibana I, Maru DM, Hawke DH, Rak J, Mani SA, Zweidler-McKay P, Ellis LM. Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype Through a Soluble Form of Jagged-1. Cancer Cell 23(2):171-85 (highlighted in Nature Cell Biology 15(4):351, 2013.), 2013. PMID: 23375636.
- Mobley A, Linder SK, Braeuer R, Ellis LM, Zwelling L. A survey on data reproducibility in cancer research provides insights into our limited ability to translate findings from the laboratory to the clinic. PLoS One 8(5):1-4, 2013. e-Pub 2013. PMID: 23691000.
- Zhou Y, Tozzi F, Chen J, Fan F, Xia L, Wang J, Gao G, Zhang A, Xia X, Brasher H, Widger W, Ellis LM, Weihua Z. Intracellular ATP Levels Are a Pivotal Determinant of Chemoresistance in Colon Cancer Cells. Cancer Res 72(1):304-14, 2012. e-Pub 2011. PMID: 22084398.
- Fan F, Samuel S, Evans KW, Lu J, Xia L, Zhou Y, Sceusi E, Tozzi F, Ye XC, Mani SA, Ellis LM. Overexpression of Snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells. Cancer Med 1(1):5-16, 2012. PMID: 2334229.
- Samuel S, Fan F, Dang LH, Xia L, Gaur P, Ellis LM. Intracrine Vascular Endothelial Growth Factor Signaling in Survival and Chemoresistance of Human Colorectal Cancer Cells. Oncogene 30(10):1205-1212, 2011. e-Pub 2010. PMID: 21057529.
- Fan F, Samuel S, Gaur P, Lu J, Dallas NA, Xia L, Bose D, Ramachandran V, Ellis LM. Chronic exposure of colorectal cancer cells to bevacizumab promotes compensatory pathways that mediate tumour cell migration. Br J Cancer 104(8):1270-1277, 2011. e-Pub 2011. PMID: 21407219.
- Samuel S, Gaur P, Fan F, Xia L, Gray MJ, Dallas NA, Bose D, Rodriguez-Aguayo C, Lopez-Berestein G, Plowman G, Bagri A, Sood AK, Ellis LM. Neuropilin-2 Mediated β-Catenin Signaling and Survival in Human Gastro-Intestinal Cancer Cell Lines. PLoS One 6(10):1-11, 2011. PMID: 22028766.
- Bose D, Zimmerman LJ, Pierobon M, Petricoin E, Tozzi F, Parikh A, Fan F, Dallas N, Xia L, Gaur P, Samuel S, Liebler DC, Ellis LM. Chemoresistant colorectal cancer cells and cancer stem cells mediate growth and survival of bystander cells. Br J Cancer 105(11):1759-67, 2011. PMID: 22045189.
- Jayson GC, Hicklin DJ, Ellis LM. Antiangiogenic therapy-evolving view based on clinical trial results. Nat Rev Clin Oncol 9(5):297-303, 2012. PMID: 22330688.
- Begley CG, Ellis LM. Drug development: Raise standards for preclinical cancer research. Nature 483:531-533, 2012.
- Bose D, Meric-Bernstam F, Hofstetter W, Reardon DA, Flaherty KT, Ellis LM. Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care. Lancet Oncol 11(4):373-382, 2010. PMID: 20171141.
- Ellis LM, Reardon DA. Is there really a yin and yang to VEGF-targeted therapies?. The Lancet Oncol 11(9):809-11, 2010.
- Ellis LM, Fidler IJ. Finding the tumor copycat. Therapy fails, patients don't. Nat Med 16(9):974-5, 2010. PMID: 20823880.
- Ellis LM, Hicklin DJ. Resistance to targeted therapies: Refining anticancer therapy in the era of molecular oncology. Clin Cancer Res 15(24):7471-7478, 2009. PMID: 20008847.