PI: Dr. Gerhard Hamilton, Associate Professor
Lab Location: Surgical Research Labs, AKH 8H
Contact: gerhard.hamilton@meduniwien.ac.at.
Tel. ++43-1-40400-6852
Focus
Our work focuses on the characterization of new anticancer drugs and the identification of molecular mechanisms involved in their mode of action and putative chemoresistance. We use in vitro models of permanent and primary human tumor cell lines and state-of-the-art assays to investigate tumor cell proliferation, modulation, cell death and signal transduction. Special consideration is given to the contributions of the tumor cell microenvironment, particularly tumor pH, which is known to influence drug distribution, uptake and intracellular effects. Methods to measure intracellular pH and calcium as well as their regulators were established and used in this research lab for decades.
Currently we are working the following subjects:
1. Apoptotic cell death in cancer therapy
This work focuses on tumor biology and drug resistance, with particular interest in neuroendocrine tumors and colon cancer. Resistance to chemotherapy is attributed to reduced apoptosis in conjunction with increased glycolysis and reduced mitochondrial function. The direct and indirect effects of dichloroaceate (DCA), a modulator that diverts glucose utilization towards respiration, is studied in respect to tumor cell inhibition and modulation of chemotherapeutic-induced cell death.
2. Intracellular tumor cell pH and metastatic potential
Growth factors like neurotensin and others induce intracellular alkalinization in colon and pancreatic cancer cells. The corresponding extracellular acidification triggers enhanced metastasis, as indicated by production of prometastatic cytokines and increased disintegration of extracellular matrix. Effects of extracellular acidification on global gene expression were investigated and the affected proteins are now under study in regard to their function in tumor cell motility and invasiveness.
3. Intracellular tumor pH and proton pump inhibitors
The intratumoral distribution of chemotherapeutic drugs has been shown to be improved following application of high concentration of proton pump inhibitors (PPIs) like omeprazole, lansoprazole and pantoprazole. Therefore we are investigating the effects of PPIs on growth and intracellular pH on tumor cells in vitro.