| Dr. Linger’s research is focused on Tyro-3, Axl, and Mer. Together, these three proteins comprise the TAM family of receptor tyrosine kinases (RTKs). The TAM RTKs are aberrantly expressed in several human cancers including leukemia, breast cancer, prostate cancer, glioblastoma, and lung cancer. Studies from other laboratories have demonstrated that expression of Axl correlates with invasive ability of human non-small cell lung cancer (NSCLC) cell lines. Furthermore, in patient samples of NSCLC, Axl overexpression has been statistically associated with metastatic disease. Our preliminary findings demonstrate that TAM RTKs, as well as the ligands which activate them, are co-expressed in many human NSCLC cell lines, suggesting that this family of RTKs may constitute an autocrine loop resulting in constitutive activity of these kinases. Additional preliminary studies indicate that inhibition of Mer or Axl increases the sensitivity of NSCLC cells to killing by chemotherapeutic agents. Using a combination of in vitro biologic assays and in vivo animal models, Dr. Linger hopes to demonstrate that the TAM receptors play key roles in the development and progression of NSCLC. Her laboratory has also developed novel biologic inhibitors of Axl and Mer tyrosine kinases and will test their efficacy in vitro and in animal models of NSCLC. Ultimately, her research using these novel biologic inhibitors may provide a new therapeutic approach for the treatment of NSCLC.
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