Stephen Gould, Ph.D.
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Contact InformationRoom 409, Physiology Building
Exosome ExchangeAnimal cells possess a pathway of intercellular vesicle traffic. This pathway, exosome exchange, involves the release of small (50-100 nm diameter) single-membrane bound vesicles and their subsequent fusion with neighboring cells. The consequence of this pathway is the delivery of membrane lipids and both membrane and cytosolic proteins from one cell to another, a process that has obvious implications for cell-cell communication. Exosome exchange plays critical roles in several physiological processes, including germ cell development, interactions between antigen presenting cells and lymphocytes, and morphogenesis. My primary interest in the exosome exchange pathway is to understand the molecular mechanisms that are involved in generating exosomal vesicles, releasing them from the cell, their attachment to neighboring cells, and the subsequent fusion between the exosome membrane and the target cell membrane. Current studies are directed at testing whether exosome formation requires the class E VPS proteins (a group of 20 proteins that involved in generating ‘reverse’ oriented vesicles at endosomal membranes) and factors that have been implicated in the fusion of late endosomes with the plasma membrane (Rab27 proteins, their effectors (Slp1, etc.), myosin V, etc.).
VirologyWe recently proposed the ‘Trojan exosome hypothesis’ (Gould et al., 2003, PNAS 100:10592-7). This hypothesis, which is supported by a wide range of empirical evidence, states that retroviruses exploit exosome exchange for (i) the synthesis of retroviral particles, and (ii) a low-efficiency pathway of horizontal transfer that does not depend on retroviral proteins. This hypothesis reconciles the current model of retrovirus-directed transmission with the unique host lipids and host proteins in retroviral particles, the host cell proteins present in retroviral particles, the complex cell biology of retroviral release, the ability of retroviruses to infect cells that lack their receptor, and the horizontal transmission of Env-deleted retroviruses. HIV is a retrovirus and HIV infection causes Acquired Immune Deficiency Syndrome (AIDS), a progressive, lethal condition associated with the loss of immunity to infectious agents and cancers. The HIV pandemic has claimed 20 million lives, brought entire societies to the brink of social, economic and political collapse, and continues to spread through human populations at an accelerating rate. Not surprisingly, testing the Trojan exosome hypothesis is my highest research priority.
Peroxisome BiogenesisMy longest running research projects involve studies of peroxisomes, a different type of organelle that exists in the cytoplasm of all eukaryotic cells. Current research efforts on peroxisome biology span the topics of peroxisomal protein import, lipid import, peroxisome division, and peroxisome-associated diseases.