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.
Baskin Lab Publications at Cornell:
- 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.
- 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).
- Tei R and Baskin JM. “Spatiotemporal Control of Phosphatidic Acid Signaling with Optogenetic, Engineered Phospholipase Ds.” J Cell Biol (2020) 219, 3, e201907013.
- Daughtry JL, Cao W, Ye J, and Baskin JM. “Clickable Galactose Analogs for Imaging Glycans in Developing Zebrafish.” ACS Chem Biol (2020) 15, 4, 318–24.
- 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.
- 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, Liang FJ, and Baskin JM. “Ex Uno Plura: Differential labeling of phospholipid biosynthetic pathways with a single bioorthogonal alcohol.” Biochemistry (2018) 57, 2, 226-230.
- 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.
- Tei R and Baskin JM. “Induced proximity tools for precise manipulation of lipid signaling.” Curr Opin Chem Biol (2021).
- Batrouni AG and Baskin JM. “The Chemistry and Biology of Phosphatidylinositol 4-Phosphate at the Plasma Membrane.” Bioorg Med Chem (2021) 40, 116190.
- Flores J*, White BM*, Brea RJ, Baskin JM†, Devaraj NK†. "Lipids: chemical tools for their synthesis, modification, and analysis." Chem Soc Rev (2020) 49, 4602–14.
- Bumpus TW*, Liang D*, and Baskin JM. “IMPACT: Imaging phospholipase D activity with clickable alcohols via transphosphatidylation.” Method Enzymol (2020) 641, 75–94.
- Bumpus TW and Baskin JM. “Getting a grip on greasy molecules.” Trends Biochem Sci (2019) 44, 7, 640–41.
- Bumpus TW and Baskin JM. “Greasing the wheels of lipid biology with chemical tools.” Trends Biochem Sci (2018) 43, 970–83.
- Baskin JM, Bumpus TW. “Methods for detection and imaging of cellular phospholipase D activity”. US Patent Application US20190085373A1 (Sept 14, 2018).
Selected Publications from Graduate & Postdoctoral Work:
- *Baskin JM, *Wu X, Christiano R, Oh M, Schauder CM, Gazzerro E, Messa M, Baldassari S, Assereto S, Biancheri R, Zara F, Minetti C, Raimondi A, Simons M, Walther TC, Reinisch KM, De Camilli P. “The leukodystrophy protein FAM126A/Hyccin regulates PI4P synthesis at the plasma membrane.” Nat Cell Biol, 18, 132–38 (2016).
- Nakatsu F*, Baskin, JM*, Chung J, Tanner LB, Shui G, Lee SY, Pirruccello M, Hao M, Ingolia NT, Wenk MR, De Camilli P. (2012) “PtdIns4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity.” J Cell Biol, 199, 1003–16 (2012).
- Baskin JM*, Dehnert KW*, Laughlin ST*, Amacher SL, Bertozzi CR. (2010) “Visualizing enveloping layer glycans during zebrafish early embryogenesis.” Proc Natl Acad Sci USA, 107, 10360–65 (2010).
- Laughlin ST*, Baskin JM*, Amacher SL, Bertozzi CR. “In vivo imaging of membrane-associated glycans in developing zebrafish.” Science, 320, 664–67 (2008).
- Codelli JA, Baskin JM, Agard NJ, Bertozzi CR. “Second-generation difluorinated cyclooctynes for copper-free click chemistry.” J Am Chem Soc, 130, 11486–93 (2008).
- Baskin JM, Prescher JA, Laughlin ST, Agard NJ, Chang PV, Miller IA, Lo A, Codelli JA, Bertozzi CR. “Copper-free click chemistry for dynamic in vivo imaging.” Proc Natl Acad Sci USA, 104, 16793–97 (2007).
- Agard NJ*, Baskin JM*, Prescher JA, Lo A, Bertozzi CR. “A comparative study of bioorthogonal reactions with azides.” ACS Chem Biol, 1, 644–48 (2006).