Ashani Weeraratna, Ph.D.
Ashani Weeraratna, Ph.D.
- Associate Professor, Tumor Microenvironment and Metastasis Program
- Member, The Wistar Institute Melanoma Research Center
- 215-495-6937, Office
The laboratory of Ashani Weeraratna focuses on unraveling the molecular mechanisms involved in melanoma metastasis with a particular emphasis on the Wnt signaling pathway, which comprises a family of proteins that have been shown to have great implications in fetal development as well as cancer. Another major interest of her laboratory lies in examining the changes in the tumor microenvironment, such as hypoxia, and aging associated senescence, and how these changes affect melanoma progression and therapy resistance.
Weeraratna became a member of The Wistar Institute in 2011 from the Laboratory of Molecular Biology and Immunology at the National Institute on Aging, which she joined in 2003 as a staff scientist becoming head of the laboratory’s Cancer Biology Unit. Born in Sri Lanka, Weeraratna was raised in Southern Africa, and her first introduction to the United States was in 1988 when she enrolled at St. Mary’s College of Maryland, a small liberal arts college on the western shore of the Chesapeake Bay, to study biology. Her growing interest in the science of cancer led her to the George Washington University Medical Center’s Department of Pharmacology, where she earned a Ph.D. in Molecular and Cellular Oncology. From 1998 to 2000, she was post-doctoral fellow at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Oncology Center, before joining the National Human Genome Research Institute as a staff scientist.
The primary focus of the Weeraratna laboratory is the study of how melanoma spreads, or metastasizes. The progression of melanoma from early to late stage involves a series of signaling changes within the cell, often described in terms of “pathways.” In particular, Weeraratna focuses on the non-canonical Wnt signaling pathway and how changes in genes and their protein products involved in this pathway can lead to changes in how malignant cells multiply, move throughout the body, and invade other tissues.
In a related course of study, Weeraratna is also extremely interested in exploring how changes in the microenvironment contribute to both tumor progression and therapy resistance. These changes may be induced changes such as chemotherapy or irradiation, or more “natural” changes such as hypoxia and aging. As an example, melanoma incidence is increased in elderly patients, who also have a worse prognosis, and this could be due to a number of age-related factors, such as decreased immunity, but may also be due to changes in the aging microenvironment. Using melanoma cells and both young and old normal skin cells as a model, Weeraratna is trying to unravel just what these changes may be, and how they affect tumor progression.
1 - Kaur A, Webster MR, Marchbank K, Behera R, Ndoye A, Kugel III CH, Dang VM, Appleton J, O’Connell MP, Cheng P, Valiga AA, Morissette R, McDonnell NB, Ferrucci L, Kossenkov AV, Meeth K, Tang H-Y, Yin X, Wood III WH, Lehrmann E, Becker KG, Flaherty KT, Frederick DT, Wargo JA, Cooper ZA, Tetzlaff MT, Hudgens C, Aird KM, Zhang R, Xu X, Liu Q, Bartlett E, Karakousis G, Eroglu Z, Lo RS, Chan M, Menzies AM, Long GV, Johnson DB, Sosman J, Schilling B, Schadendorf D, Speicher DW, Bosenberg M, Ribas A, and Weeraratna AT. sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance. Nature, In Press.
2 - Webster MR, Xu M, Kinzler KA, Kaur A, Appleton J, O'Connell MP, Marchbank K, Valiga A, Dang VM, Perego M, Zhang G, Slipicevic A, Keeney F, Lehrmann E, Wood W 3rd, Becker KG, Kossenkov AV, Frederick DT, Flaherty KT, Xu X, Herlyn M, Murphy ME, Weeraratna AT. Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells. Pigment Cell Melanoma Res. 2015; 28: 184-195. PMCID: PMC4333017.
3 - O’Connell MP, Marchbank K, Webster MR, Valiga AA, Kaur A, Vultur A, Li L, Herlyn M, Villanueva J, Liu Q, Yin X, Widura S, Nelson J, Ruiz N, Camilli TC, Indig FE, Flahery KT, Wargo JA, Frederick DT, Cooper ZA, Nair S, Amaravadi RK, Schuchter LM, Karakousis GC, Wei X, Xu X, Weeraratna AT. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Discov. 2013; 3: 1378-1393. PMCID: PMC3918498.
4 - Camilli T.C., Xu M., O'Connell M.P., Chien B., Frank B.P., Subaran S., Indig F.E., Morin P.J., Hewitt S.M.,Weeraratna A.T. Loss Of Klotho During Melanoma Progression Leads To Increased Filamin Cleavage, Increased Wnt5A Expression and Enhanced Melanoma Cell Motility. Pigment Cell Melanoma Res. 24 (1) 175-86. 2011.
5 - O’Connell, M.P., Fiori J.L., Indig, F.E., Frank B.P., Dissanayake, S.K., French, A.D., Carter A., Camilli T.C., Earley, R., Taub, D.D., Bernier, M. , Hewitt, S.M. and Weeraratna, A.T. The Expression and Internalization of the Orphan Tyrosine Kinase Receptor, ROR2, is Regulated by Wnt5A/PKC signaling in Metastatic Melanoma. Oncogene, 29(1):34-44. 2010.
6 - O’Connell, M.P., Fiori, J.L., Kershner, E.K., Frank B.P., Indig, F.E., Taub, D.D., Hoek K.S., and Weeraratna, A.T. HSPG Modulation of Wnt5A Signal Transduction in Metastatic Melanoma Cells. J. Biol. Chem, 284(42):28704-12. 2009.
7 - Dissanayake, S.K., Olkhanud, P.B., O’Connell, M.P., Carter, A. , French, A.D., Camilli, T.C., Emeche, C.D., Hewitt, K.J., Rosenthal, D.T. , Leotlela, P.D., Wade, M.S., Yang, S.W., Brant, L, Nickoloff, B.J., Messina, J.L., Biragyn, A, Hoek, K.S., Taub, DD, Longo, D.L., Sondak, V.K., S.M., Hewitt, Weeraratna, AT. Wnt5A Regulates Expression of Tumor Associated Antigens in Melanoma Via Changes in STAT3 Phosphorylation. Cancer Res 68(24):10205-14, 2008. 27.
8 - Dissanayake, S. K., Wade, M. S., Johnson, C. E., O'Connell, M. P., Leotlela, P. D., A.D., F., Shah, K. V., Hewitt, K. J., Rosenthal, D. T., Indig, F. E., Jiang, Y., Nickoloff, B. J., Taub, D. D., Trent, J. M., Moon, R. T., Bittner, M., and Weeraratna, A. T. The Wnt5A/ PKC Pathway Mediates Motility In Melanoma Cells Via The Inhibition Of Metastasis Suppressors, And Initiation Of An Epithelial To Mesenchymal Transition. J Biol Chem, 282(23):17259-71, 2007.
9 - Leotlela PD, Wade MS, Duray PH, Rhode MJ, Brown HF, Rosenthal DT, Dissanayake SK, Earley R, Indig FE, Nikoloff BJ, Taub DD, Kallioniemi OP, Meltzer P, Morin PJ, and Weeraratna AT. Claudin-1 Overexpression In Melanoma Is Regulated By PKC And Contributes To Melanoma Cell Motility. Oncogene, 26(26):3846-56, 2007.
10 - Weeraratna AT, Jiang Y, Hostetter G., Rosenblatt K, Duray P, Bittner M and Trent JM. Wnt5a signaling directly affects the motility and invasion of melanoma cells. Cancer Cell, 1(3): 279-288. 2002.