Every single one of our 40 trillion cells must execute an intricate yet precise molecular
choreography at its surface membrane. In this way cells synchronize the uptake of nutrients,
processing of signals, building of tissues and even triggering the cells’ own demise. Viewed
from such a perspective, most diseases that affect the human body are intriguing because they
influence only some of these processes, leaving most unperturbed. Consider a cancer cell; it
grows uncontrollably and refuses to die due to aberrant signaling mechanisms, yet maintains
the capacity to move and nourish itself. Our lab studies a vital family of lipid molecules, the
inositol lipids, that normally regulate and coordinate these essential membrane processes. We
uncover fundamental new mechanisms that explain how these molecules choreograph
membrane function, and – crucially – why some lipid-dependent functions fail in disease, while
others are spared. To do this, we develop novel probes and tools using genetic engineering to
probe living cell membranes in real time under the microscope. Some current projects include:
- Mapping the molecular organization of the membrane during normal physiology, and how this
changes during oncogenic signaling. We use cutting-edge super-resolution and single
molecule imaging approaches to accomplish this. We aim to identify the composition of
specific molecular complexes that might be targetable with drugs to disrupt oncogenic
signaling.
- Working out the detailed control mechanisms for lipid signaling in smooth muscle cells, and
how this is altered during diseases like hypertension and asthma. A combination of chemical
and molecular genetics is used here, along with traditional biochemical and novel single-cell
assays. We aim to identify new drug targets to control smooth muscle cell contraction in these
diseases.
- Identifying how aberrant accumulation of signaling lipids leads to targeted disruption of cellular
function, and what mechanisms could be brought into play to correct this. The aim is to apply
this knowledge to genetic diseases that cause aberrant lipid accumulation, leading to diseases
as diverse as neurodegeneration and polycystic kidney disease. We apply a range of state-ofthe-
art gene editing and novel chemical genetic tools to study this problem at the single cell
level.