Rina Plattner, Ph.D.

Bio / Education: 

B.A. Colorado College; 1985
Ph.D. Indiana University School of Medicine; 1992
Postdoctoral Fellowship, University of California Irvine, Stanbridge Lab, 1992-1996
Postdoctoral Fellowship, Duke University, Pendergast Lab, 1997-2003

Research Description: 

The Plattner laboratory studies the process of cancer metastasis. Most cancer deaths result from metastatic spread to distant organ sites. In no cancer type is this most striking than in melanoma. The cure rate for small, thin, non-metastatic melanomas is >95%; however, once melanomas have metastasized, the 5-year survival rate drops to 10% and the mean survival time is 6-9 months. Although melanoma only accounts for 5% of skin cancers, it results in 75% of skin cancer-related deaths. Great strides have been made in detection and prevention; however, melanoma diagnoses still are on the rise, particularly in young adults. Despite nearly 40 years of clinical trials, there has been little improvement in survival rates for patients with metastatic melanoma. However, an exciting development in the last 3 years is the identification of a novel drug, which targets a genetic mutation in melanoma (B-Raf). Vemurafemib, as it is called, shows promise for the treatment of metastatic disease as it prolongs survival. However, some melanomas do not have B-Raf mutations, some are intrinsically resistant to the drug, others acquire resistance during treatment, and even in responding patients, survival is < 10 months. Thus, new drugs are critically needed for treating this disease.

The Plattner laboratory has identified the Abl family of non-receptor tyrosine kinases (c-Abl, Arg) as novel drug targets for breast cancer and melanoma. These kinases are most known for their involvement in the development of human leukemia (such as chronic myelogenous leukemia-CML). Gleevec/imatinib, an inhibitor of the Abl family, was one of the first “smart” drugs developed, and is currently standard of care treatment for patients with CML. Significantly, the Plattner laboratory was the first to demonstrate that, in addition to leukemia, Abl kinases also play a critical role in solid tumors, such as melanoma and breast cancer, indicating that drugs targeting these kinases may also be effective for treating these diseases. Seminal work from the laboratory showed that Abl kinases are highly activated in some breast cancers and melanomas, and their activation contributes to cancer proliferation, survival following nutrient deprivation, anchorage-independent growth, invasion, and metastasis. Current studies in the laboratory are aimed at understanding how the Abl family contribute to melanoma and breast cancer progression. The laboratory utilizes cancer cell lines (in vitro studies), animal models (in vivo studies), and patient samples to identify novel signaling pathways by which the Abl family promotes cell motility, invasion, and metastasis. The laboratory also is identifying drugs that may cooperate with Abl family inhibitors to shrink melanoma/breast cancer growth and prevent metastatic progression.

Grants: 

NIH CA166499

Current Positions of Former Students

Sourik Ganguly, (Ph.D., 2013), postdoctoral fellow, Van Andel Research Inst., Grand Rapids, MI
Jonathan Sims, (Ph.D., 2012), Research Scientist, Lilly Research Labs, Indianapolis, IN
Jessica Tepe (undergraduate research student, 2010), graduate student, Emory U., Atlanta, GA
Divya Srinivasan (Ph.D., 2009), Staff Pharmacist, BRHS Hospital, Lake Jackson, TX

PubMed Publications: 

  • Zhao, H.;Chen, M.S.;Lo, Y.H.;Waltz, S.E.;Wang, J.;Ho, P.C.;Vasiliauskas, J.;Plattner, R.;Wang, Y.L.;Wang, S.C. "The Ron receptor tyrosine kinase activates c-Abl to promote cell proliferation through tyrosine phosphorylation of PCNA in breast cancer." Oncogene 33, 11 (2014): 1429-37. [PubMed Link] | [ Full text ]
  • Fiore, L.S.;Ganguly, S.S.;Sledziona, J.;Cibull, M.L.;Wang, C.;Richards, D.L.;Neltner, J.M.;Beach, C.;McCorkle, J.R.;Kaetzel, D.M.;Plattner, R. "c-Abl and Arg induce cathepsin-mediated lysosomal degradation of the NM23-H1 metastasis suppressor in invasive cancer." Oncogene (2013): [PubMed Link] | [ Full text ]
  • Sims, J.T.;Ganguly, S.S.;Bennett, H.;Friend, J.W.;Tepe, J.;Plattner, R. "Imatinib reverses doxorubicin resistance by affecting activation of STAT3-dependent NF-κB and HSP27/p38/AKT pathways and by inhibiting ABCB1." PloS one 8, 1 (2013): e55509. [PubMed Link] | [ Full text ]
  • Ganguly, S.S.;Plattner, R. "Activation of abl family kinases in solid tumors." Genes & cancer 3, 5-6 (2012): 414-25. [PubMed Link] |
  • Ganguly, S.S.;Fiore, L.S.;Sims, J.T.;Friend, J.W.;Srinivasan, D.;Thacker, M.A.;Cibull, M.L.;Wang, C.;Novak, M.;Kaetzel, D.M.;Plattner, R. "c-Abl and Arg are activated in human primary melanomas, promote melanoma cell invasion via distinct pathways, and drive metastatic progression." Oncogene 31, 14 (2012): 1804-16. [PubMed Link] | [ Full text ]
  • Zhao, H.;Ou-Yang, F.;Chen, I.F.;Hou, M.F.;Yuan, S.S.;Chang, H.L.;Lee, Y.C.;Plattner, R.;Waltz, S.E.;Ho, S.M.;Sims, J.;Wang, S.C. "Enhanced resistance to tamoxifen by the c-ABL proto-oncogene in breast cancer." Neoplasia (New York, N.Y.) 12, 3 (2010): 214-23. [PubMed Link] |
  • Srinivasan, D.;Kaetzel, D.M.;Plattner, R. "Reciprocal regulation of Abl and receptor tyrosine kinases." Cellular signalling 21, 7 (2009): 1143-50. [PubMed Link] | [ Full text ]
  • Sims, J.T.;Ganguly, S.;Fiore, L.S.;Holler, C.J.;Park, E.S.;Plattner, R. "STI571 sensitizes breast cancer cells to 5-fluorouracil, cisplatin and camptothecin in a cell type-specific manner." Biochemical pharmacology 78, 3 (2009): 249-60. [PubMed Link] | [ Full text ]
  • Sims, J.T.;Plattner, R. "MTT assays cannot be utilized to study the effects of STI571/Gleevec on the viability of solid tumor cell lines." Cancer chemotherapy and pharmacology 64, 3 (2009): 629-33. [PubMed Link] | [ Full text ]
  • Mitra, S.;Beach, C.;Feng, G.S.;Plattner, R. "SHP-2 is a novel target of Abl kinases during cell proliferation." Journal of cell science 121, Pt 20 (2008): 3335-46. [PubMed Link] | [ Full text ]
  • Srinivasan, D.;Sims, J.T.;Plattner, R. "Aggressive breast cancer cells are dependent on activated Abl kinases for proliferation, anchorage-independent growth and survival." Oncogene 27, 8 (2008): 1095-105. [PubMed Link] | [ Full text ]
  • Srinivasan, D.;Plattner, R. "Activation of Abl tyrosine kinases promotes invasion of aggressive breast cancer cells." Cancer research 66, 11 (2006): 5648-55. [PubMed Link] | [ Full text ]
  • Plattner, R.;Koleske, A.J.;Kazlauskas, A.;Pendergast, A.M. "Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor." Molecular and cellular biology 24, 6 (2004): 2573-83. [PubMed Link] | [ Full text ]
  • Burton, E.A.;Plattner, R.;Pendergast, A.M. "Abl tyrosine kinases are required for infection by Shigella flexneri." The EMBO journal 22, 20 (2003): 5471-9. [PubMed Link] | [ Full text ]
  • Plattner, R.;Irvin, B.J.;Guo, S.;Blackburn, K.;Kazlauskas, A.;Abraham, R.T.;York, J.D.;Pendergast, A.M. "A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1." Nature cell biology 5, 4 (2003): 309-19. [PubMed Link] | [ Full text ]
  • Plattner, R.;Kadlec, L.;DeMali, K.A.;Kazlauskas, A.;Pendergast, A.M. "c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF." Genes & development 13, 18 (1999): 2400-11. [PubMed Link] | [ Full text ]
  • Plattner, R.;Pendergast, A.M. "Activation and signaling of the Abl tyrosine kinase: bidirectional link with phosphoinositide signaling." Cell cycle (Georgetown, Tex.) 2, 4 (1969): 273-4. [PubMed Link] | [ Full text ]
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