Team Leader: Cancer Cell Biology Laboratory
Dr Georgios Giamas obtained his Biology degree (BSc) at the National and Kapodistrian University of Athens in Greece. He then undertook his Doctoral degree (PhD - Magna Cum Laude) at the University of Ulm (Germany). Following 9 months of postdoctoral work at the University of Ulm, he moved to Imperial College London at 2007, working as a Research Associate till 2010. In 2011 he was awarded Imperial College’s prestigious Junior Research Fellowship. In 2012 he was awarded a NIHR Senior Research Fellowship and was appointed as a Research Team Leader in the Division of Cancer.
Research Interests: The interplay of kinases and phosphatases in cancer
Dr Giamas’s group is focused on identifying novel kinases and phosphatases and elucidate their role and contribution in the development of cancer.
Protein kinases are relevant in intracellular signal transduction, with more than 150 already implicated in disease development . Dr Giamas's team has identified Lemur Tyrosine Kinase 3 (LMTK3) as a regulator of ERα with prognostic and predictive significance for breast cancer (BC) patient survival (Giamas et al., 2011-Nature Medicine / Stebbing et al., 2012-BCRT), also possessing roles in innate (intrinsic) and acquired (adaptive) endocrine resistance in BC (Stebbing et al., 2012-Oncogene).
Over two-thirds of breast tumors express the Estrogen Receptor-alpha (ERα) and patients with ERα+ disease respond to anti-estrogens (tamoxifen-(Tam)), estrogen withdrawal (aromatase inhibitors) or ERα downregulation (fulvestrant). However, resistance frequently occurs with tumours recurring as metastatic. Mutations in ERα are rarely found; instead other mechanisms have been associated with tamoxifen resistance, among them phosphorylation of ERα. Apart from regulating transcriptional activity of ERα, phosphorylation at multiple sites also alters its stability.
Moreover, Tam-resistant ERα+ cells exhibit a transition towards a more aggressive phenotype displaying augmented motility and invasiveness. Accumulating evidence suggests that ERα extra-nuclear signaling (cross-talk with kinases and phosphatases) can promote cell migration and metastasis.
Taken together, we believe that deciphering the mechanisms of LMTK3 action will reveal fundamental insights into the role of ERα signaling in endocrine resistance and metastasis, and derive new druggable targets.
Schematic of research work.
Clarifying the molecular, functional and regulatory properties of LMTK3 (aim 1) will provide us with additional information that will help us elucidate the involvement of LMTK3 in the regulation of ERα (aim 2) as well as its contribution in the development ERα-dependent and ERα-independent mediated metastatic processes (aim 3). In parallel with these goals, we will be working in identifying novel kinase inhibitor(s) for LMTK3 (aim 4) that can be used i ultimately in the future for in vivo and pre-clinical studies.
et al., 2019, Endocrine Resistance in Hormone Receptor Positive Breast Cancer-From Mechanism to Therapy, Frontiers in Endocrinology, Vol:10, ISSN:1664-2392
et al., 2018, Shedding of bevacizumab in tumour cells-derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma, Molecular Cancer, Vol:17, ISSN:1476-4598
et al., 2018, LMTK3 confers chemo-resistance in breast cancer, Oncogene, Vol:37, ISSN:0950-9232, Pages:3113-3130
et al., 2017, Extracellular vesicles swarm the cancer microenvironment: from tumor-stroma communication to drug intervention, Oncogene, Vol:36, ISSN:0950-9232, Pages:877-884
et al., 2017, MSLN gene silencing has an anti-malignant effect on cell lines overexpressing mesothelin deriving from malignant pleural mesothelioma (vol 9, e85935, 2014), Plos One, Vol:12, ISSN:1932-6203