Research in the Baskin group centers on pioneering innovative chemical approaches to probe the biology of lipids and membranes, with a major focus on developing new molecular imaging tools and elucidating biological mechanisms relevant to human disease.
Lipids are the hydrophobic molecules that our bodies use to store energy, insulate us from the cold, and build membranes that act as selectively permeable barriers to encapsulate our cells and their organelle compartments. The most abundant type of membrane lipids are phospholipids, which number in the thousands of individual molecular species. The abundant phospholipids control bulk properties of the membrane, including fluidity, curvature, and permeability, whereas the rare phospholipids can act as drivers of signaling pathways by binding to proteins and modulating their bioactivities. Our research centers on these rare, low-abundance signaling phospholipids, which are fascinating and mysterious biological molecules. Though, largely, their biosynthetic enzymes have long ago been discovered and characterized biochemically, major questions have persisted for decades about the biology of these phospholipids: Where are they produced in the cell? How are they transported from their place of synthesis to their ultimate destination? How do cells control the activity of the enzymes that produce them? How do cells get the ‘right’ signal from individual lipids that have a multitude of different bioactivities? How does dysfunction in lipid homeostasis contribute to human disease? We address these questions using interdisciplinary approaches rooted in chemical biology. We have developed chemical technologies to visualize and manipulate specific types of signaling lipids and applied these tools to begin to answer some of these questions. We have also engaged in hypothesis-driven research to understand basic and disease-associated mechanisms related to cancer, neurological diseases, and infection. Collectively, our tools and discoveries have shed new light on important fundamental mechanisms in lipid and membrane biology and opened up new potential treatments for diseases featuring dysfunction in these processes.
Please see a complete publication list on the Baskin Lab website.
Selected publications from the Baskin Lab:
- Bumpus TW, Huang S, Tei R, and Baskin JM. “Click chemistry–enabled CRISPR screening reveals GSK3 as a regulator of PLD signaling.” Proc Natl Acad Sci USA (2021) 118, 48, e2025265118.
- Tei R*, Morstein J*, Shemet A, Trauner D†, and Baskin JM†. “Optical control of phosphatidic acid signaling.” ACS Cent Sci (2021) 7, 7, 1205–1215. *Equal contribution; †Co-corresponding authors.
- Liang D, Cheloha R, Watanabe T, Gardella TJ, and Baskin JM. “Activity-based, bioorthogonal imaging of phospholipase D reveals spatiotemporal dynamics of GPCR-Gq signaling.” Cell Chem Biol (2021) 28, 1–7.
- Shami Shah A, Cao X, White AC, Baskin JM. “PLEKHA4 Promotes Wnt/β-catenin Signaling-Mediated G1/S Transition and Proliferation in Melanoma.” Cancer Res (2021) 81, 2029–43.
- Tei R and Baskin JM. “Spatiotemporal Control of Phosphatidic Acid Signaling with Optogenetic, Engineered Phospholipase Ds.” J Cell Biol (2020) 219, 3, e201907013.
- Liang D, Wu K*, Tei R*, Bumpus TW, Ye J, and Baskin JM. “A real-time, click chemistry imaging approach reveals stimulus-specific subcellular locations of phospholipase D activity.” Proc Natl Acad Sci USA (2019) 116, 31, 15453–62. *Equal contribution.
- Shami Shah A, Batrouni AG, Kim D, Punyala A, Cao W, Han ML, Smolka MB, and Baskin JM. “PLEKHA4/kramer attenuates Dishevelled ubiquitination to modulate Wnt and planar cell polarity signaling.” Cell Rep (2019) 27, 2157–70.
- Bumpus TW and Baskin JM. “Clickable Substrate Mimics Enable Imaging of Phospholipase D Activity.” ACS Cent Sci (2017) 3, 10, 1070-1077.
- Bumpus TW and Baskin JM. “A Chemoenzymatic Strategy for Imaging Cellular Phosphatidic Acid Synthesis.” Angew Chem Int Ed (2016) 55, 13155-13158.