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Scott Joseph Goldman
Veterinariae Medicinae Doctoris (V.M.D.) 2003
University of Pennsylvania
Thesis Advisor: Shengkan Jin, Ph.D.
Graduate Program: Cellular and Molecular Pharmacology
Rutgers Life Sciences Building Auditorium
Busch Campus, Piscataway
Friday, June 18, 2010
Autophagy is a process of macromolecular intracellular degradation highly conserved among eukaryotic organisms. In recent decades, our understanding of the ever- increasing list of the functions of autophagy has blossomed, and we now know of key roles played by autophagy in a wide variety of physiological and pathological conditions. Despite this, two widely used models of autophagy deficiency, the atg5 -/- primary mouse fibroblast and the beclin 1 +/- transgenic mouse, are not nearly as well characterized as one would expect. The purpose of the work presented in this thesis is the further identification andevaluation of phenotypic differences betwee wild-type cells and organisms and their autophagy deficient or insufficient counterparts. The data presented hereafter illustrates that autophagy plays important roles in adipocyte differentiation, hepatic cholesterol metabolism homeostasis, and cellular growth rate maintenance. Additionally, in an effort to develop an autophagy-insufficient tumorigenic mouse in which tumors could be non-invasively imaged, we have established a novel tumor imaging model in which spontaneously developing tumors may be imaged in their native environent. Importantly, this model allows us to non-invasively monitor tumor growth and response to treatment in immunocompetent mice without resorting to the use of xenografts orallografts.