Possible Rotation Projects:
- 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.
Training Technologies Used:
- Fluorescence imaging
- Confocal microscopy
- Single molecule imaging
- Single particle tracking
- Automated computational image analysis
- Ph.D (Biochemistry). 2005. University College London, UK
- B.Sc (Cell Biology). 2001. University College London, UK
Swayhoover T, Weckerly CC, Hammond GRV. Quantitative comparison of PI(3,5)P(2) biosensors reveals SnxA is the most sensitive and unbiased. Mol Biol Cell. 2026 Aug 5;:mbcE26030120. doi: 10.1091/mbc.E26-03-0120. [Epub ahead of print] PubMed PMID: 42555823.
Duewell BR, Worcester M, Chirumbolo MJ, Beam A, Fernandez-Ortiz SM, Hammond GRV, Hansen SD. PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization. Proc Natl Acad Sci U S A. 2026 Jul 28;123(30):e2529784123. doi: 10.1073/pnas.2529784123. Epub 2026 Jul 22. PubMed PMID: 42485385; PubMed Central PMCID: PMC13416441.
Worcester M, Ricci MMC, Weckerly CC, Calixto JG, Hammond GRV. The cell biologist's guide to detecting and modulating membrane phospholipids. J Cell Biol. 2026 Feb 2;225(2). doi: 10.1083/jcb.202508058. Epub 2026 Jan 2. Review. PubMed PMID: 41481227.
Weckerly CC, Rahn TA, Ehrlich M, Wills RC, Pemberton JG, Airola MV, Hammond GRV. PILS-Nir1 is a sensitive phosphatidic acid biosensor that reveals mechanisms of lipid production. J Cell Biol. 2025 Nov 3;224(11). doi: 10.1083/jcb.202405174. Epub 2025 Sep 9. PubMed PMID: 40923975; PubMed Central PMCID: PMC12419160.
Holmes VL, Ricci MMC, Weckerly CC, Worcester M, Hammond GRV. Single-molecule lipid biosensors mitigate inhibition of endogenous effector proteins. J Cell Biol. 2025 Mar 3;224(3). doi: 10.1083/jcb.202412026. Epub 2025 Feb 11. PubMed PMID: 39932556; PubMed Central PMCID: PMC11812570.
Doyle CP, Timple L, Hammond GRV. OSBP is a Major Determinant of Golgi Phosphatidylinositol 4-Phosphate Homeostasis. Contact (Thousand Oaks). 2024 Jan-Dec;7:25152564241232196. doi: 10.1177/25152564241232196. eCollection 2024 Jan-Dec. PubMed PMID: 38405037; PubMed Central PMCID: PMC10893830.
Doyle CP, Rectenwald A, Timple L, Hammond GRV. Orthogonal Targeting of SAC1 to Mitochondria Implicates ORP2 as a Major Player in PM PI4P Turnover. Contact (Thousand Oaks). 2024 Jan-Dec;7:25152564241229272. doi: 10.1177/25152564241229272. eCollection 2024 Jan-Dec. PubMed PMID: 38327560; PubMed Central PMCID: PMC10848804
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.
