Education

Biography

Suranganie Dharmawardhane Flanagan is a Full Professor and Graduate Student Coordinator in the Department of Biochemistry at the University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico. Dr. Flanagan, has an experience in teaching for 35 years as an associate professor, assistant professor, Senior Research Associate, and as a Teaching Assistant. The research focus of  her laboratory is molecular mechanisms of signal transduction during breast cancer metastasis. This research program includes characterization of natural and pharmacological inhibitors of cancer metastasis. Dr. Flanagan use human breast cancer cell lines and immunocompromised mice to study the molecular mechanisms of red wine polyphenols, soy isoflavones, and chemotherapeutics targeted at epidermal growth factor receptors and the Rho GTPases Rac and Cdc42. New directions involve the role of non-coding RNAs in breast cancer therapy resistance. Dr. Flanagan has received awards and honors, as Distinguished Teacher Award and Scientist Development Award.

Research Interests

Research interests are breast cancer metastasis and the preventive and therapeutic role of natural and synthetic anti-metastasis compounds. Expertise in breast cancer research include biochemical and molecular analysis of novel therapeutics in breast cancer cell and mouse models, with a focus on epidermal growth factor receptor (EGFR)/HER2 signaling, and the Rho GTPases Rac and Cdc42 and their downstream effector P2-activated kinase (PAK) as therapeutic targets.

Scientific Activities

Teaching Experience

Professional Activities

• American Association of Cancer Research
• Minorities in Cancer Research, reviewer 2007-2008 Selection Committee for Minority Scholars in Cancer Research
• American Society of Cell Biologists
• American Society for Biochemistry and Molecular Biology

Honors & Awards

Publications

1. Humphries-Bickley, T, Castillo-Pichardo, L, Hernandez-O-Farrill, E, Borrero-Garcia, LD, Forestier-Roman, I, Gerena, Y, Blanco, M, Rivera-Robles, MJ, Rodriguez-Medina, JR, Cubano, LA, Vlaar, CP, and Dharmawardhane, S. 2017. Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer. Mol Cancer Therap. MS# MCT-16-0442R, in press.
2. Rivera-Rivera, A, Castillo-Pichardo, L, Gerena, Y, Dharmawardhane, S. 2016. Anti breast cancer potential of quercetin via the Akt/mTOR/AMPK/Mammalian Target of Rapamycin (mTOR) signaling cascade. PLoS One 11:e0157251.
3. de La Parra, C, Castillo-Pichardo, L, Cruz-Collazo, A, Cubano, LA, Redis, R, Calin, GA, Dharmawardhane, S. 2016. Soy isoflavone genistein-mediated downregulation of miR-155 contributes to the anticancer effects of gensitein. Nutr cancer, 68:154-164.
4. Humphries-Bickley, T. Castillo-Pichardo, L, Corujo-Carro, F, Duconge, J, Hernandez-O-Farrill, Vlaar, C, Rodriguez-Orengo, J, Cubano, L, Dharmawardhane, S. 2015, Pharmacokinetics of Rac inhibitor EHop-016 in mice by ultra-performance liquid chromatography tandem mass spectrometry. J Chromatogr. B Analyt. Technol. Biomed. Life Sci. 981-982:19-26.
5. deLa Parra, C, Borrero-Garcia, LD, Cruz-Collazo, A, Schneider, RJ, Dharmawardhane, S. 2015, Equol, an isoflavone metabolite, increases cancer progression via upregulation of c-Myc and protein synthesis initiation. Journ Biological Chemistry, 290(10):6047-57.
6. Cekanova M, Fernando RI, Siriwardhana N, Sukhthankar M, Parra C, Woraratphoka J, Malone C, Ström A, Baek SJ, Wade PA, Saxton AM, Donnell RM, Pestell RG, Dharmawardhane S, Wimalasena J. 2015, Bcl2 family protein BAD is down regulated in breast cancer and inhibits cell invasion. Exp Cell Res. 331(1):1-10.
7. Castillo-Pichardo, L. Humphries-Bickley T, De La Parra C, Forestier-Roman I, Martinez-Ferrer M, Hernandez E, Vlaar C, Ferrer-Acosta Y, Washington AV, Cubano LA, Rodriguez-Orengo J,Dharmawardhane S. 2014, The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude Mouse Model. Transl. Oncol. 7, 546-555.
8. Castillo-Pichardo, L, Dharmawardhane, S, and Rodríguez-Orengo, JF. 2014. Rapid quantification of resveratrol in mouse plasma by ultra high pressure liquid chromatography (UPLC) coupled to tandem mass spectrometry. PR Health Sci. J. 33:151-156.
9. Ramos, G, Loperena, Y, Ortiz, G, Reyes, F, Szeto, A, Vera, JVelez, J, Morales, J, Morrero, D, Castillo, L, Dharmawardhane, S, Melendez, E, and Washington AV. 2014, A pregnenolone pendant group enhances the anticancer properties of titanocene dichloride in a MCF-7 Xenograph model, Anticancer Res, 34(4):1609-1615.
10. Martin, H, Mali, RS, Ma, P, Chatterjee, A, Ramdas, B, Sims, E, Munugalavadla, V, Ghosh, J, Mattingly, RR, Visconte, V, Tiu, RV, Vlaar, CP, Dharmawardhane, S, and Kapur, R., 2013.PAK and Rac GTPases promote oncogenic KIT-induced neoplasms. Journ. Clin. Invest. 123(10):4449-4463.
11. Castillo-Pichardo L, Rivera-Rivera A, Dharmawardhane S., 2013. Potential of grape polyphenols as breast cancer therapeutics. OA Altern. Med. Apr 01;1(1):9. Dharmawardhane, Su 10
12. Castillo-Pichardo, L, Cubano, LA, Dharmawardhane, S., 2013. Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice. BMC Complement. Altern. 13:6.
13. de la Parra, C, Otero-Franqui, E, Martinez-Montemayor, M, Dharmawardhane, S, 2012, The soy isoflavone equol may increase cancer malignancy via upregulation of eukaryotic protein synthesis initiation factor eIF4G. J Biol. Chem., 287: 41640-41650.
14. Castillo-Pichardo, L, Dharmawardhane, S., 2012, Grape polyphenols inhibit Akt/mTOR signaling and potentiate the effects of gefitinib in breast cancer, Nut. Cancer, 64:1058-69.
15. Montalvo-Ortiz, BL, Castillo-Pichardo, L, Hernández, E, De La Mota-Peynado, A, Humphries-Bickley, T, Vlaar, CP, and Dharmawardhane, S. 2012, Characterization of EHop-016, a novel small molecule inhibitor of Rac GTPase. Journ. Biol. Chem, 287(16):13228-38.
16. Martínez-Montemayor, MM, Rosario Acevedo, R, Otero-Franqui, E, Cubano, L, Dharmawardhane, S., 2011. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer, Nut. Cancer, 63 (7):1085-1094.
17. Hernandez, E, De La Mota-Peynado, A., Dharmawardhane, S., and Cornelis Vlaar, 2010. Novel inhibitors of Rac1 in metastatic breast cancer PRHealth Sc. J., 29 (4):348-356.
18. Martínez-Montemayor, MM, Martinez, JE, Otero-Franqui, E., De La Mota-Peynado, A., Cubano, LA, and Dharmawardhane, S., 2010. Individual and Combined Soy Isoflavones Exert Differential Effects on Metastatic Cancer Progression. Clin. Exp. Metastasis, 27:465-480.
19. Castillo-Pichardo, L, Martinez-Montemayor, M, Martinez, J, Wall, K, Cubano L, and Dharmawardhane S., 2009. Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols. Clin. Exp. Metastasis, 26: 505-16.
20. Schlachterman, A, Valle, V, Wall, K, Azios, N, Castillo, L, Morell, L, Washington, AV, Cubano L, and Dharmawardhane S, 2008. Red wine polyphenols reduce breast tumor growth in a nude mouse model. Translational Oncol., 1:19-27.
21. Calabria, LM, Piacente, S, Kapusta I, Dharmawardhane, SF, Segarra, FM, Pessiki, PJ, Mabry, TJ. 2008. Triterpene saponins from Silphium radula. Phytochemistry, 69:961-972.
22. Azios, N.G., Harris, M., Krishnamoorthy, L., Cammer, M., Cubano, L., Dharmawardhane, S. 2007. Estrogen and Resveratrol Regulate Rac and Cdc42 Signaling to the Actin Cytoskeleton of Metastatic Breast Cancer Cells. Neoplasia, 9:147-158.
23. Sokolov, K., Nida, D., Descour, M., Levy, M., Hall, B., Dharmawardhane, S., Ellington, A., Korgel, B., Richards-Kortum, R. 2006. Molecular optical imaging of therapeutic targets of cancer. Adv Cancer Res, 96:299-344.
24. Carlson, A.L, Hoffmeyer, M.R., Wall, K., Baugher, P.J., Richards-Kortum, R., Dharmawardhane, S. 2006. In situ analysis of breast cancer progression in murine models using a macroscopic fluorescence imaging system. Lasers in Medicine and Surgery, 38:928-938.
25. Baugher, P., Krishnamoorty, L., Price, J. and Dharmawardhane, S. 2005. Rac1 and Rac3 regulate breast cancer cell invasion and metastasis in metastatic variants of MB-435 human breast cancer cells. Breast Cancer Res., 7:R965-R974.
26. Hoffmeyer, M.R., Wall, K., Dharmawardhane, S. 2005. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line, Cancer Cell Int., 5:11.
27. Azios, N.G., Dharmawardhane, S. 2005. Resveratrol and estradiol exert disparate effects on cell migration, cell surface actin structures, and focal adhesion assembly in MDA-MB-231 human breast cancer cells. Neoplasia 7:128-140.
28. Hsu, E. R., Anslyn, E.V., Dharmawardhane, S.F., Gillenwater, A.M., Alizadeh-Naderi, R., Aaron, J.S., Sokolov, K.V., El-Naggar, A.K., Richards-Kortum, R. 2004. A far-red fluorescent contrast agent molecularly targeted against epidermal growth factor receptor. Photochem. Photobiol. 79(3), 272-279.
29. Brownson, Azios, N., Fuqua, B., Dharmawardhane, S. *, and Mabry, T. 2002. (*corresponding author) Flavanoid effects relevant to cancer. J. Nutrition 132:3482S-3489S.
30. Lacey, A., Collier, T., Price, J., Dharmawardhane, S., and Richards-Kortum, R., 2002. Near real-time in vivo confocal imaging of mouse mammary tumors. Front. Biosci. 7:F1-7 Dharmawardhane, Su 11
31. Dharmawardhane, S., Sells, M.A., Chernoff, J., Schmid, S., and Bokoch, G.M. 2000. Regulation of macropinocytosis by p21-activated kinases. Mol. Biol. Cell, 11:3341-3352.
32. Dharmawardhane, S., Brownson, D., Lennartz, M., and Bokoch, G.M. 1999. Localization of PAK 1 to lamellipodia and phagocytic cups in activated human neutrophils. J. Leuk. Biol. 66:521-526.
33. Dharmawardhane, S., Sanders, L., Martin, S., Daniels, R.H., and Bokoch, G.M. 1997. Localization of p21-activated kinase 1 (PAK 1) to pinocytic vesicles and cortical actin structures in stimulated cells. J. Cell Biol., 138:1265-1278.
34. Rietdorf, J., Siegert, F., Dharmawardhane, S., Firtel, R.A. and Weijer, C.J., 1997. Analysis of cell movement and signalling during ring formation in an activated G1 mutant of Dictyostelium discoideum that is defective in prestalk zone formation. Devel. Biol. 181:79-90.
35. Dharmawardhane, S. & Bokoch, G., 1997. Rho family GTPases and Leukocyte Cytoskeletal Regulation. Curr. Opin. Hematol. 4:12-18.
36. Dharmawardhane, S., Cubitt, A.B. Clark, A.M., & Firtel, R.A., 1994. Regulatory role of Ga1 subunit in controlling cellular morphogenesis in Dictyostelium. Development, 120:3549-3561.
37. Carrel, F., Dharmawardhane, S., Clark, A.M., Powell-Coffman, J.A. & Firtel, R.A. 1994. Spatial and temporal expression of the Dictyostelium Ga protein subunit Ga2: Expression of a dominant negative protein inhibits proper prestalk to stalk differentiation. Mol.Biol.Cell. 5:7-16.
38. Schatzle, J., Bush,J., Dharmawardhane, S., Firtel, R., Gomer, R., & Cardelli,J. 1993. Characterization of the signal transduction pathways and cis-acting DNA sequence responsible for the transcriptional induction during growth and development of the lysosomal a-Mannosidase gene in Dictyostelium discoideum. J. Biol.Chem. 268:19632-19639.
39. Cubitt, A.B., Dharmawardhane, S., & Firtel, R.A., 1993. Developmentally regulated changes in 1,2- Diacylglycerol in Dictyostelium. Regulation by light and G proteins. J.Biol.Chem. 268:17431-17439.
40. Dharmawardhane, S., Demma, M., Yang, F., & Condeelis, J., 1991. Compartmentalization and actin binding of ABP-50, the elongation factor-1 a from Dictyostelium. Cell Motil. Cytosk. 20:279-288.
41. Yang, F., Demma, M., Warren, V., Dharmawardhane, S., & Condeelis, J., 1990. Identification of an actin binding protein from Dictyostelium as elongation factor-1 a. Nature 347:494-496.
42. Condeelis, J., Bresnick, A., Demma, M., Dharmawardhane, S., Eddy, R., & Warren, V., 1990. Mechanisms of amoeboid chemotaxis: An evaluation of the cortical expansion model. Dev. Genet. 11:333-340.
43. Demma, M., Warren, V., Hock, R., Dharmawardhane, S., & Condeelis, J., 1990. Isolation of an abundant 50,000 dalton actin filament bundling protein from Dictyostelium amoebae. J. Biol. Chem. 265:2286-2291.
44. Hall, A.L., Warren, V., Dharmawardhane, S., & Condeelis, J., 1989. Transduction of the chemotactic signal to the actin cytoskeleton of Dictyostelium discoideum. Dev. Biol. 136:517-525.
45. Hall, A.L., Warren, V., Dharmawardhane, S., & Condeelis, J., 1989. Identification of actin nucleation activity and polymerization inhibitor in different fractions of chemotactic amoebae. J. Cell Biol. 109:2207-2214.
46. Dharmawardhane, S., Warren, V., Hall, A.L., & Condeelis, J., 1989. Changes in the association of actin binding proteins with the actin cytoskeleton during chemotactic stimulation of Dictyostelium discoideum. Cell Motil. Cytosk. 13:57-63.
47. Dharmawardhane, S., Rubinstein, B., & Stern, A.I., 1989. Regulation of transplasmalemma electron transport in oat mesophyll cells by sphingoid bases and blue light. Plant Physiol. 89:1345-1350.
48. Dharmawardhane, S., Stern, A.I., & Rubinstein, B., 1987. Light-stimulated transplasmalemma electron transport of oat mesophyll cells. Plant Sc. 51:193-201.