THE KOH LABORATORY
Innovating tomorrow's therapies
Themes
We study molecular aberrations in tumour cells and their microenvironment.
Our goal is to turn tumour-specific features into druggable vulnerabilities.
Targeting the DNA damage response
Defects in the DNA damage response (DDR) pathway render some cancer cells vulnerable to exogenous insults, a concept that underpins the use of chemotherapy. However, because of their lack of target selectivity, many chemotherapeutic agents operate within a narrow therapeutic window. A strategy to redress this issue is the development of molecularly targeted agents that exploit cancer-specific abnormalities. Our work shows that inhibiting cell cycle kinases such as ATR, CHK1 and WEE1 is an effective way to capitalise on DDR defects in cancer cells.
Reversing drug resistance
While tumours may initially respond to treatment, drug resistance often develops, leading to disease progression or relapse. Through analyses of primary and preclinical tumour samples, our work demonstrates that identifying potential predictive biomarkers can guide the selection of effective therapies from the outset. We are also studying how tumour cells manipulate their microenvironment—specifically, the surrounding immune cells—to become drug-resistant. The ultimate goal is to systematically target both tumour-intrinsic and -extrinsic factors that contribute to drug resistance.
Building better tools
The success of science relies on the availability and advances of research tools. We are interested in creating experimental molecules, models and methods that are applicable to the pipeline of drug discovery and development. Our work so far has generated predictive approaches for lead optimisation, dose-response effects and drug-drug interactions, as well as high-content microscopy systems and analytical platforms. These tools continue to help us discover new details about cancer behaviours and drug mechanisms of action.
