Our goal is to understand the processes that generate compartments of the secretory pathway, including ER exit sites (ERES; also known as transitional ER or tER sites) and the cisternae of the Golgi apparatus. Self-organization models provide the conceptual framework. Specifically, we postulate that ERES are generated together with early Golgi cisternae by an integrated self-organization pathway, and that early cisternae progressively mature into late cisternae.
For exploring these ideas, our main experimental system is a pair of budding yeasts. In Saccharomyces cerevisiae, Golgi cisternae are dispersed throughout the cytoplasm and the ER contains multiple small ERES, whereas in Pichia pastoris, ordered Golgi stacks are located next to large, stable ERES. These two yeasts have complementary advantages for testing specific hypotheses about the secretory pathway. We use a combination of genetics, molecular biology, 4D confocal microscopy, and electron tomography. This work is revealing evolutionarily conserved principles of cellular organization.
A second project in the lab involves optimizing fluorescent proteins, including the red fluorescent protein DsRed. Wild-type DsRed matures very slowly. We overcame this problem by using directed evolution to create the first rapidly maturing DsRed variants, one of which is marketed commercially as DsRed-Express. More recent work yielded a noncytotoxic variant called DsRed-Express2, as well as a far-red variant called E2-Crimson. These engineering efforts inspired a basic research project in which we clarified the pathway of DsRed chromophore formation. Current efforts are focused on creating improved monomeric green and red fluorescent proteins.
Biozentrum, University of Basel
Basel, Switzerland
(postdoc) - Cell Biology
1994
Stanford University
Stanford, CA
PhD - Biochemistry
1988
Amherst College
Amherst, MA
BA - Neuroscience / Mathematics
1983
Yellow and oxidation-resistant derivatives of a monomeric superfolder GFP.
Yellow and oxidation-resistant derivatives of a monomeric superfolder GFP. bioRxiv. 2024 Jan 26.
PMID: 38328041
Editorial overview: Membranes in perpetual motion.
Editorial overview: Membranes in perpetual motion. Curr Opin Cell Biol. 2022 Oct; 78:102128.
PMID: 36103730
Clathrin adaptors mediate two sequential pathways of intra-Golgi recycling.
Clathrin adaptors mediate two sequential pathways of intra-Golgi recycling. J Cell Biol. 2022 01 03; 221(1).
PMID: 34739034
Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome. Elife. 2021 09 21; 10.
PMID: 34545811
TRAPP structures reveal the big picture.
TRAPP structures reveal the big picture. EMBO J. 2021 06 15; 40(12):e108537.
PMID: 34018213
A General Method to Improve Fluorophores Using Deuterated Auxochromes.
A General Method to Improve Fluorophores Using Deuterated Auxochromes. JACS Au. 2021 May 24; 1(5):690-696.
PMID: 34056637
Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway.
Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway. Sci Rep. 2021 01 21; 11(1):2013.
PMID: 33479349
ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms.
ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms. Mol Biol Cell. 2020 12 15; 31(26):2892-2903.
PMID: 33112725
Bioreactor-scale cell performance and protein production can be substantially increased by using a secretion signal that drives co-translational translocation in Pichia pastoris.
Bioreactor-scale cell performance and protein production can be substantially increased by using a secretion signal that drives co-translational translocation in Pichia pastoris. N Biotechnol. 2021 Jan 25; 60:85-95.
PMID: 33045421
Predictors of pressure injury development in critically ill adults: A retrospective cohort study.
Sala JJ, Mayampurath A, Solmos S, Vonderheid SC, Banas M, D'Souza A, LaFond C. Predictors of pressure injury development in critically ill adults: A retrospective cohort study. Intensive Crit Care Nurs. 2021 Feb; 62:102924.
PMID: 18332110