Stephen Gould, Ph.D.

Professor

410-955-3424

Affiliation: Professor of Biological Chemistry

Description of Research

Research in the Gould lab is focused on the intersection of cell biology, bioengineering, and human disease.

Mechanisms of exosome biogenesis

Exosomes are small secreted vesicles of ~100 nm in size that play critical roles in human health and disease. We study the molecular mechanisms of exosome biogenesis by interrogating the biogenesis, intracellular trafficking, and vesicular secretion of highly enriched exosome cargo proteins, as well as viral proteins that use the hosts’ exosome biogenesis pathways for the formation of infectious viruses. Most recently, we’ve discovered that exosome marker proteins all bud primarily from the plasma membrane, and moreover, that endocytosis of exosome marker proteins from the plasma membrane greatly inhibits their vesicular secretion. These results re-write our understanding of exosome biogenesis by showing that it occurs primarily by direct budding from the plasma membrane, with only minor contributions from exocytosis of internal vesicles (Ai et al. Science Advances 2024, https://www.science.org/doi/10.1126/sciadv.adi9156).

Cell and exosome engineering

As the only bionormal nanovesicle, exosomes are an ideal delivery vehicle for vaccines, biologics, and drugs. Our laboratory uses our latest advances in exosome biogenesis to create proteins that are efficiently loaded into exosomes and confer unique properties on recombinantly engineered exosomes, including induction of immune responses, inhibition of angiogenesis, and other biomedically important activities. We then drive the high-level production of recombinant exosome-targeted proteins using new, highly restrictive antibiotic resistance genes that allow us to rapidly create cell lines that express the highest possible levels of recombinant proteins.

Synthetic signaling systems

Together with Dr. Michael Caterina’s lab, we’ve invented synthetic signaling systems that convert pathogenic signaling pathways into tunable, negative feedback loops that attenuate their pathogenic effects. These genetically-encoded tools are designed to ameliorate chronic diseases, with our primary focus on developing a safe and effective treatment for chronic pain.