Fusheng Tang
Assistant Professor
(501) 569-3507
(501) 569-3271 (fax)
fxtang@ualr.edu
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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
Research Interests
Vacuolar Membrane Organization
Molecular Biology of Aging
Cellular Systems Biology
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. 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 recently observed that
the vacuolar membrane of aged cells tend to invaginate (arrows in Figure), an indication
of alterations in membrane organization. Therefore, my laboratory is devoted to understanding
lysosomal/vacuolar membrane dynamics during aging by a combination of genetics, biochemistry,
and systems biology approaches.
Sterol transport to and from the vacuolar membrane: While blocking sterol synthesis
fragments vacuoles and shortens life span, up-regulating sterol synthesis does not always remedy
the vacuolar morphology and extend the life span, suggesting that sterol transport plays a key
role in vacuolar membrane organization. In addition to vesicle-mediated transport, the
oxysterol-binding protein (OSBP) family transports 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.
Age-dependent vacuolar alterations: The functional overlap of the sterol-transporting
proteins poses a challenge for reductive approaches to identify the proteins that transport
sterols to and from the vacuolar membrane. Studying vacuolar membrane aging from an integrative
perspective will guide the traditional approaches. The vast amount of '-omics' data and extensive
knowledge about membrane trafficking to the vacuolar membrane provide unique opportunities to
reconstruct a vacuole 'in silico', an integrative database of vacuolar membrane proteins and
lipids where the relationships of key proteins and lipids are mathematically simulated. This
'virtual' vacuole can serve as a scaffold for in silico genetic manipulation of vacuolar membrane
proteins and lipids (top-down systems biology) and mathematical modeling of the kinetics of
age-dependent alterations of membrane curvature or functions (bottom-up systems biology). Manipulations
(gene deletion, over-expression, etc) that theoretically boost the sterol transport to and from
the vacuolar membrane in aged cells will be tested by in vivo and in vitro analyses.
These hand-in-hand wet lab and dry lab interactions will elucidate the mechanisms governing vacuolar
membrane homeostasis during aging. Moreover, the conservation of vacuolar functions will further
allow us to reconstruct the 'virtual' lysosomes and design advanced drug or food interventions targeted
to the lysosomal membrane aging process.
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Selected publications
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Tang F, Watkins JW, Bermudez M, Gray R, Gaban A, Portie K, Grace S, Kleve M, Craciun G. 2008. A life-span extending form of autophagy employs the vacuole-vacuole fusion machinery. Autophagy. 4(7):874-886.
Liu W, Tang F. 2008. Modeling a simplified regulatory system of blood glucose at molecular levels. J Theor Biol. 252(4):608-620.
Mete M, Tang F, Xu X, Yuruk N. 2008. A structural approach for finding functional modules from large biological networks. BMC Bioinformatics. 9 (Suppl 9):S19.
Tang F, Peng Y, Nau JJ, Kauffman EJ, Weisman LS. 2006. Vac8p, an armadillo repeat protein, coordinates vacuole inheritance with multiple vacuolar processes. Traffic. 7(10):1368-1377.
Tang, F., Kauffman, E.J., Novak, J.L., Nau, J.J., Catlett, N.L. and Weisman, L.S. (2003) Regulated degradaton of a class V myosin receptor directs movement of the yeast vacuole. Nature. 422:87-92.
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