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Robert R Langley, Ph.D.

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

Microvascular endothelial cells play a critical role in the initiation and perpetuation of a number of pathophysiologic processes, including cancer. Studies have shown that tumor cells exploit cytokine-inducible endothelial cell glycoproteins to promote their retention in target organs of metastasis and then recruit resident endothelial cells to form new vascular networks (i.e., angiogenesis) in order to ensure tumor growth and survival. Because tumor cell arrest and angiogenesis are regarded as key, rate-limiting steps in metastasis, much of my research has focused on an improved understanding of the cellular and molecular interactions that take place between tumor cells and vascular endothelial cells. To advance our studies, we established a broad panel of microvascular endothelial cell lines from different tissues of the mouse. These cell lines have enabled us to define the molecular basis of therapy and to identify those growth factors most likely to stimulate endothelial cell division in different tissues. This type of information is valuable in that it can be used to predict which antiangiogenic strategy would be most beneficial for a given anatomic region. We have also been interested in developing in vitro models of the tumor-associated blood vasculature in order to identify new targets for anticancer therapy. To this end, we recently developed a methodology for generating constitutively active ligand-independent chimeric receptors and have shown that when this receptors are introduced into endothelial cells, the user can identify intracellular effectors that may serve as potential targets for therapy.

Education & Training

Degree-Granting Education

2000 Louisiana State University Medical Center School of Medicine, Shreveport, LA, PHD, Molecular and Cellular Physiology
1989 Louisiana State University Medical School of Allied Health Professions, Shreveport, LA, BS, Cardiopulmonary Science

Honors and Awards

2003 Scholar-in-Training Award, AFLAC-American Association for Cancer Research
2002 Asche-Murray Fellowship Award in Ovarian Cancer Research, MD Anderson Cancer Center, Houston, TX
1999 Outstanding Instructor in Physiology, Louisiana State University Health Sciences Center, Shreveport, LA

Professional Memberships

American Association for Cancer Research
Member, 2001-present
Histochemical Society
Member, 2005-present
Metastasis Research Society
Member, 2002-present

Selected Publications

Peer-Reviewed Original Research Articles

1. Chintalgattu V, Rees ML, Culver JC, Goel A, Jiffar T, Zhang J, Dunner K, Pati S, Bankson JA, Pasqualini R, Arap W, Bryan NS, Taegtmeyer H, Langley RR, Yao H, Kupferman ME, Entman ML, Dickinson ME, Khakoo AY. Coronary microvascular pericytes are the cellular target of sunitinib malate-induced cardiotoxicity. Sci Transl Med 5(187):187ra69, 5/29/2013. PMID: 23720580.
2. Langley RR, Fidler IJ. The Biology of Brain Metastasis. Clin Chem. e-Pub 10/2012. PMID: 23115057.
3. Rangel R, Guzman-Rojas L, le Roux LG, Staquicini FI, Hosoya H, Barbu EM, Ozawa MG, Nie J, Jr KD, Langley RR, Sage EH, Koivunen E, Gelovani JG, Lobb RR, Sidman RL, Pasqualini R, Arap W. Combinatorial targeting and discovery of ligand-receptors in organelles of mammalian cells. Nat Commun 3:788, 2012. PMID: 22510693.
4. Han C, Wan G, Langley RR, Zhang X, Lu X. Crosstalk between the DNA damage response pathway and microRNAs. Cell Mol Life Sci 69(17):2895-2906, 2012. PMID: 22430204.
5. Hu W, Lu C, Dong HH, Huang J, Shen DY, Stone RL, Nick AM, Shahzad MM, Mora E, Jennings NB, Lee SJ, Roh JW, Matsuo K, Nishimura M, Goodman BW, Jaffe RB, Langley RR, Deavers MT, Lopez-Berestein G, Coleman RL, Sood AK. Biological roles of the Delta family notch ligand Dll4 in tumor and endothelial cells in ovarian cancer. Cancer Res 71(18):6030-9, 9/2011. PMCID: PMC3174342.
6. Kim SW, Kim JS, Papadopoulos J, Choi HJ, He J, Maya M, Langley RR, Fan D, Fidler IJ, Kim SJ. Consistent interactions between tumor cell IL-6 and macrophage TNF-a enhance the growth of human prostate cancer cells in the bone of nude mouse. Int Immunopharmacol 11(7):862-72, 7/2011. PMCID: PMC3086935.
7. Langley RR, Fidler IJ. The seed and soil hypothesis revisited-the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 128(11):2527-35, 6/2011. PMCID: PMC3075088.
8. Guo L, Fan D, Zhang F, Price JE, Lee JS, Marchetti D, Fidler IJ, Langley RR. Selection of brain metastasis-initiating breast cancer cells determined by growth on hard agar. Am J Pathol 178(5):2357-66, 5/2011. PMCID: PMC3081177.
9. Lu C, Han HD, Mangala LS, Ali-Fehmi R, Newton CS, Ozbun L, Armaiz-Pena GN, Hu W, Stone RL, Munkarah A, Ravoori MK, Shahzad MM, Lee JW, Mora E, Langley RR, Carroll AR, Matsuo K, Spannuth WA, Schmandt R, Jennings NB, Goodman BW, Jaffe RB, Nick AM, Kim HS, Guven EO, Chen YH, Li LY, Hsu MC, Coleman RL, Calin GA, Denkbas EB, Lim JY, Lee JS, Kundra V, Birrer MJ, Hung MC, Lopez-Berestein G, Sood AK. Regulation of Tumor Angiogenesis by EZH2. Cancer Cell 18(2):185-197, 8/2010. PMID: 20708159.
10. Chintalgattu V, Ai D, Langley RR, Zhang J, Bankson JA, Shih TL, Reddy AK, Coombes KR, Daher IN, Pati S, Patel SS, Pocius JS, Taffet GE, Buja LM, Entman ML, Khakoo AY. Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress. J Clin Invest 120(2):472-84, 2/2010. e-Pub 1/2010. PMCID: PMC2810076.
11. Rebhun RB, Cheng H, Gershenwald JE, Fan D, Fidler IJ, Langley RR. Constitutive expression of the alpha4 integrin correlates with tumorigenicity and lymph node metastasis of the B16 murine melanoma. Neoplasia 12(2):173-82, 2/2010. PMCID: PMC2814355.
12. Brantley EC, Guo L, Zhang C, Lin Q, Yokoi K, Langley RR, Kruzel E, Maya M, Kim SW, Kim SJ, Fan D, Fidler IJ. Nitric oxide-mediated tumoricidal activity of murine microglial cells. Transl Oncol 3(6):380-8, 2010. e-Pub 12/1/2010. PMCID: PMC3000463.
13. Lahat G, Zhu QS, Huang KL, Wang S, Bolshakov S, Liu J, Torres K, Langley RR, Lazar AJ, Hung MC, Lev D. Vimentin is a novel anti-cancer therapeutic target; insights from in vitro and in vivo mice xenograft studies. PLoS One 5(4):e10105, 2010. PMCID: PMC2855704.
14. Langley RR, Guo L, Fan D, McCartey JF, Lin Q, Zhang F, Maya M, Fidler IJ. Generation of an immortalized astrocyte cell line from H-2Kb-tsA58 mice to study the role of astrocytes in brain metastasis. Intl J Oncology 35:665-672, 9/2009. PMCID: PMC2882684.
15. Sasaki T, Nakamura T, Rebhun RB, Cheng H, Hale KS, Tsan RZ, Fidler IJ, Langley RR. Modification of the primary tumor microenvironment by transforming growth factor alpha-epidermal growth factor receptor signaling promotes metastasis in an orthotopic colon cancer model. Am J Pathol 173(1):205-16, 7/2008. PMCID: PMC2438298.
16. Fidler IJ, Kim SJ, Langley RR. The role of the organ microenvironment in the biology and therapy of cancer metastasis. J Cell Biochem 101(4):927-36, 7/1/2007. PMID: 17177290.
17. Langley RR, Fidler IJ. Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocr Rev 28(3):297-321, 5/2007. PMID: 17409287.
18. Rebhun RB, Langley RR, Yokoi K, Fan D, Gershenwald JE, Fidler IJ. Targeting receptor tyrosine kinase on lymphatic endothelial cells for the therapy of colon cancer lymph node metastasis. Neoplasia 8(9):747-57, 9/2006. PMID: 16984732.
19. Langley RR, Cheng H, Wu Q, Wu W, Feng J, Tsan R, Fan D, Fidler IJ. Construction of a novel constitutively active chimeric EGFR to identify new targets for therapy. Neoplasia 7(12):1065-72, 12/2005. PMID: 16354589.
20. Nilsson MB, Langley RR, Fidler IJ. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 65(23):10794-800, 12/2005. PMID: 16322225.
21. Langley RR, Fan D, Tsan RZ, Rebhun R, He J, Kim SJ, Fidler IJ. Activation of the platelet-derived growth factor-receptor enhances survival of murine bone endothelial cells. Cancer Res 64(11):3727-30, 6/2004. PMID: 15172974.
22. Langley RR, Ramirez KM, Tsan RZ, Van Arsdall M, Nilsson MB, Fidler IJ. Tissue-specific microvascular endothelial cell lines from H-2K(b)-tsA58 mice for studies of angiogenesis and metastasis. Cancer Res 63(11):2971-6, 6/2003. PMID: 12782605.
23. Langley RR, Russell J, Eppihimer MJ, Alexander SJ, Gerritsen M, Specian RD, Granger DN. Quantification of murine endothelial cell adhesion molecules in solid tumors. Am J Physiol 277(3 Pt 2):H1156-66, 9/1999. PMID: 10484438.

Book Chapters

1. Fan D, Kim SJ, Langley RR, Fidler IJ. Metastasis and drug resistance. In: Drug Resistance in Cancer Cells. Ed(s) Mehta, Siddik. Springer: New York, 21-52, 2009.
2. Kim SJ, Baker CH, Kitadai Y, Nakamura T, Kuwai T, Sasaki T, Langley R, Fidler IJ. The pathogenesis of cancer metastasis: relevance to therapy. In: Principles of Cancer Biotherapy, 5. Ed(s) Oldham RK, Dillman RO. Kluwer Academic Publishers: London, UK, 17-40, 2009.
3. Fidler IJ, Baker CH, Yokoi K, Kuwai T, Nakamura T, Nilsson M, Busby JE, Langley RR, Kim, SJ. Targeting the tumor microenvironment (stroma) for the treatment of metastasis. In: Angiogenesis: An Integrative Approach from Science to Medicine. Ed(s) Figg W, Folkman J. Springer: New York, 259-270, 2008.
4. Langley, RR, Kim, SJ, Fidler, IJ. The use of orthotopic models to validate antivascular therapies for cancer. In: Tumor Angiogenesis: Basic Mechanisms and Cancer Therapy. Ed(s) D. Marmé, N. Fuesenig. Springer-Verlag: Germany, 477-490, 2008.
5. Fidler IJ, Langley RR, Kerbel RS, Ellis LM. Biology of Cancer: Angiogenesis. In: Cancer: Principles and Practice of Oncology, 7th. Ed(s) DeVita, Hellman, Rosenberg, 129-137, 2005.
6. Langley RR. Phenotypic diversity of tumor endothelial cells: targeting the tumor vasculature. In: Microvascular Research: Biology and Pathology. Ed(s) D. Shepro, 961-967, 2005.

Grant & Contract Support

Funding Source: NIH/NHLBI
Role: Investigator
Duration: 7/1/2010 - 6/30/2015

Last updated: 2/17/2014