Ph. D. (Biochemistry) 2002 The University of Iowa.
M. Sci (Genetics) 1987 Institute of Genetics, Chinese Academy of Sciences
B. Sci. (Biology) 1984 Central China Normal University

Dr. Fusheng Tang: UALR Faculty Excellence

Research Interests

Many diseases depend on age. A few approaches such as caloric restriction are now known to delay the onset of these diseases and to extend lifespan. However, the mechanisms of aging and age-dependent alterations of the cell, the composing unit of organisms, remain active areas of research.

Inside cells, proteins and even organelles are constantly subjected to adverse stimuli and become irreversibly damaged. These damaged proteins or organelles are digested by lysosomes in mammalian cells and vacuoles in yeast cells via autophagy. Proper lysosomal/vacuolar degradation depends on multiple transporting pathways to the lysosome/vacuole (cytoplasm-to-vacuole, multi-vesicular body pathway, macroautophagy, etc). These multiple pathways raise a question as to how cells maintain the physicochemical identity of the vacuolar membrane. We observed that the vacuolar membrane of aged cells tend to invaginate (arrows in Figure), an indication of alterations in membrane organization. Intriguingly, Cuervo’s group reported that the level of cholesterol in lysosomal membranes in aged rat liver cells decreases while the total cellular cholesterol level increases (Kiffin et al., 2007, JCS 120:752). Therefore, my laboratory is devoted to understanding how cells maintain the sterol homeostasis in lysosomal/vacuolar membranes during aging by a combination of genetics, biochemistry, and systems biology approaches.

Sterol transport to and from the lysosomal/vacuolar membrane: While selected sterol synthesis mutants show fragmented vacuoles and shorted life span under caloric restriction, up-regulating sterol synthesis does not always remedy the vacuolar morphology defect and extend the life span, suggesting that sterol transport also plays key roles in vacuolar membrane organization. In addition to vesicle-mediated transport, the oxysterol-binding protein (OSBP) and its related proteins transport sterols among different organelles. Deletion of selected OSBP-homologous (OSH) genes alters vacuolar morphology and the organismal life span. Whether controlling the expression of these OSH genes remedies the vacuolar membrane defects in aged cells and extends the life span is being tested. Whether mammalian OSBPs transport sterols to and from the lysosomal membranes is also being tested in our lab. The effect of down-regulating or up-regulating OSBPs on the lysosomal membrane organization will be tested by the localization of the lysosomal membrane-associated protein LAMP2, a protein enriched in cholesterol-rich microdomains, and lysosomal functions including autophagy.

Identification of longevity genes with systems biology approaches: Since multiple cellular pathways contribute to vacuolar/lysosomal membrane aging, genes involved in longevity are often elusive to traditional single-factor approaches. Thus, we are inventing systems biology tools to identify genes responsible for vacuolar/lysosomal membrane organization and longevity. In collaboration with computer scientists and mathematicians, we are using both top-down (bioinformatics analyses of genome-wide data) and bottom-up (mathematical modeling of kinetics data) approaches of systems biology in our search for longevity genes.

These hand-in-hand wet lab and dry lab interactions will elucidate mechanisms governing sterol homeostasis in lysosomal/vacuolar membranes during aging.  Read more....