The Chidley lab employs unbiased genetic screening, chemical biology, biochemistry, and cell biology tools to elucidate molecular mechanisms underlying the biology of bioactive molecules, metabolites, and drugs with the long-term ambition of addressing disease via effective and safe therapies.
We focus on exploring transporter proteins, particularly solute carriers (SLCs), and their role in shuttling nutrients and drugs across impermeable cellular membranes. These transporters act as crucial bridges between environments, playing a vital role in maintaining cellular homeostasis and influencing cellular drug responses. Using genetic screening technologies, we aim to match metabolites and drugs with their respective transporters, map nutrient dependencies across environments and uncover proteins regulating compartment-specific metabolite levels. By studying these transporters, we gain insights into the composition of the environment surrounding cells and the demands of intracellular metabolism. We are especially interested in understanding how the nutrient profile of the tumor microenvironment influences cancer cell proliferation and resistance to therapy. We primarily use human cell culture as our experimental system, with mouse models used occasionally. Overall, we seek to advance our understanding of the role of transporters and their substrates in normal cells and in disease, guide the development of strategies to suppress tumor growth, and support precision medicine efforts in cancer therapy by revealing determinants of drug sensitivity and resistance.
Example of questions we are interested in:
How are metabolites fueling cancer cells imported into cells?
What are the functions of essential orphan nutrient transporters?
How are drugs imported/exported and how does the tumor microenvironment affect drug sensitivity?
How does the environment influence cellular proliferation via nutrient/metabolite availability?
How are metabolites compartmentalized between cellular organelles?
How do the various cell types in the tumor microenvironment influence cancer cell proliferation?
For further information about our recent work please see Chidley et al, Nature Cell Biology, 2024.
