Stephen Gould, Ph.D.

Dr. Gould’s research interests lie at the intersection of biochemistry, cell biology, bioengineering, and human disease. At present, our lab is active in four major research areas: (1) elucidating the molecular mechanisms of exosome biogenesis; (2) using our understanding of exosome biogenesis to create engineered exosome-based tools, vaccines, and therapeutics;  (3) developing expression-dependent strategies to reverse pathogenic cell phenotypes in chronic pain and other diseases; and (4) improving our tools and technologies for selecting transgenic mammalian cells.

1. Exosome biogenesis

Exosomes are small secreted vesicles that play critical roles in normal cell function and human disease. To better understand how these vesicles are produced, our lab studies the intracellular trafficking and vesicular secretion of exosome marker proteins. Using this approach, we’ve found that exosome marker proteins bud primarily from the plasma membrane, that endocytosis of exosome marker proteins inhibits their vesicular secretion, and that the exosome biogenesis factor syntenin promotes the vesicular secretion of CD63 by blocking its endocytosis. Ongoing projects involve our continued interrogation of this new hypothesis of exosome biogenesis, as well as the extent to which exosome biogenesis is a cargo-driven process.

2. Exosome engineering

Elucidating the major pathway of exosome biogenesis has allowed our lab to design and produce recombinantly engineered vesicles for use as tools, probes, vaccines, and therapies. Current exosome engineering projects involve creating (a) control vesicles for neurodegeneration research, (b). pseudo-hepatitis C virus (HCV) vesicles that carry E1E2 proteins for use as probes in HCV research (in collaboration with Dr. Justin Bailey), (c) neoantigen-display vesicles for use as cancer vaccines (in collaboration with Dr. Elizabeth Jaffee), and (d) vesicle-based vaccines for protection against respiratory viruses (in collaboration with Dr. Andrew Pekosz).

3. Expression-dependent therapies for chronic pain and other diseases

Our laboratory is developing expression-dependent therapies that fight disease by re-wiring intracellular signaling pathways of specific cell types that control disease outcomes. These studies include our development of adeno-associated virus (AAV)-delivered, sensory nerve-targeted inhibitors of chronic pain signaling pathways, to treat chronic pain (in collaboration with Dr. Michael Caterina), and AAV-delivered, T-cell-targeted inhibitors of immunosuppressive signaling pathways, to treat immunosuppression in cancers and infectious disease (in collaboration with Dr. Drew Pardoll).

4. Inventing new tools and technologies for selecting transgenic cells

The selection of transgenic mammalian cells enables a wide array of basic science research, and is also key to the production of protein-based therapeutics. However, current tools and technologies are inefficient. Our lab is developing novel sets of SM genes that solve these inefficiencies, including restrictive SM genes directly select for elevated transgene expression, and protein expression and cell transgenesis (ProtECT) systems that rapidly select for the highest possible level of linked transgene expression.