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Research Interests
Dr. Porszasz-Reisz is conducting two research projects in her laboratory:
1. Muscle wasting is a characteristic of a number of diseases, including cancer cachexia, sepsis, HIV-infection, diabetes, aging, spinal cord injury, starvation, and end-stage kidney, heart and pulmonary disease. It can cause generalized weakness and debilitation and in its extreme, when respiratory muscles are involved, asphyxia and even death. Muscle wasting, among other things, is characterized as a derangement in size and number of muscle fibers. Muscle function depends on fiber numbers, fiber size, and Myosin Heavy Chain (MHC) isoforms composition of the skeletal muscle. Myostatin (Mst) is a member of the transforming growth factor-beta (TGF-?) family that negatively regulates skeletal muscle mass, modulates transcription of muscle-specific genes, keeps muscle progenitor (satellite) cells in a quiescent state, inhibits muscle regeneration, inhibits proliferation and differentiation of myoblast, and downregulates DNA and protein synthesis. We are interested in looking at the relationship myostatin has with muscle structure and function in physiologic conditions in adult mice.
Mst and/or its downstream effectors are regarded as a good drug target since therapeutics that modulate skeletal muscle growth are useful for disease conditions with muscle loss. Our research enhances the understanding of the role and regulatory features of Mst and improve the potential for therapeutic solutions for muscle wasting.
2. Obesity, one of the most prevalent, serious, and preventable chronic disorders in industrialized societies, has been established as a characteristic of the western lifestyle. The prevalence of obesity among US adults increased to 20.9% in 2001, a 5.6% increase in 1 year and a 74% increase since 1991 (CDC, Department of Health and Human Services surveillance). Lipids are essential for energy homeostasis, reproduction and organ physiology, and numerous other aspects of cellular biology. However, the excess accumulation in various tissues is linked to many pathological processes such as obesity, heart disease, and inflammation. The storage of an overabundance of fat in skeletal muscle, liver, and other insulin-responsive tissue and organs, most notoriously adipose tissue, is attributed to the onset of type 2 diabetes, hypertension, and hyperlipidemia, which together are associated with the metabolic syndrome. The accumulation of excess fat predisposes skeletal muscle to the development of insulin resistance, a hallmark feature of type 2 diabetes. Skeletal muscle is capable of adapting metabolically and morphologically to changing environmental stimuli, allowing it to better meet the energy demands of sustained physical activity. Mst has been shown to have a significant role as a promoter in adipogenesis, and it profoundly regulates mesenchymal stem cell differentiation, such as the inhibition of adipogenesis and myogenesis and bone morphogenic proteins (BMPs) can promote chondrogenesis, osteogenesis, and adipogenesis. Studies conducted in this laboratory have shown that Mst overexpression increased fat mass and decreased muscle mass as adults. Delineating the regulation of fat mass by Mst signaling in skeletal muscle may be beneficial in the prevention and reversal of metabolic disorders, such as insulin resistance and obesity, through increased lipid catabolism in muscle and decreased lipid accumulation of adipose tissue.
Using animal models to study human diseases is an essential part of basic and clinical research. The ability to manipulate the genome of mice by knocking out genes, introducing new genetic information into fertilized eggs of transgenic mice by injection of DNA, or by targeting mutations to specific genes opened up exciting, new challenges in these research areas and instigated unique approaches to study gene functions and interactions.
In the past decade, Dr. Porszasz-Reisz developed and used genetically modified mouse models in her above described two projects. One is the myostatin overexpressing transgenic model, the other is the conditional myostatin overexpressing transgenic model. In the latter model, the gene is not simply overexpressing in the skeletal muscle, but it is possible to turn it ON (conditional transgenic model) by simple pharmacological means. The advantage of the conditional transgenic animal model is that the gene of interest could be turned ON at different ages, enabling us to answer some questions related to human aging.
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SOME RELEVANT PUBLICATIONS
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Artaza* JN, Reisz-Porszasz* S, Dow JS, Kloner RA, Tsao J, Bhasin S, Gonzalez-Cadavid NF 2007.
Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse. J Endocrinol. 194(1):63-76. (*equal authorship). [Abstract]
Magee TR, Artaza JN, Ferrini MG, Zuniga FI, Cantini L, Reisz-Porszasz S, Rajfer J, Gonzalez-Cadavid NF, 2006. Myostatin short hairpin RNA gene therapy increases muscle mass. Journal of Gene Medicine 8(9):1171-1181. [abstract]
Artaza JN, Bhasin S, Magee TR, Reisz-Porszasz S, Shen R, Groome NP, Fareez MM, Gonzalez-Cadavid NF. 2005. Myostatin Inhibits Myogenesis and Promotes Adipogenesis in 10T (1/2) Mesenchymal Multi-potent cells. Endocrinology 146(8):3547-57. [abstract]
Reisz-Porszasz S, Bhasin S, Artaza JN, Shen R, Sinha-Hikim I, Hogue A, Fielder TJ, Gonzalez-Cadavid NF. 2003. Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am J Physiol Endocrinol Metab. 285(4):E876-88.[abstract]
Beischlag TV, Wang S, Rose DW, Torchia J, Reisz-Porszasz S, Muhammad K, Nelson WE, Probst MR, Rosenfeld MG, Hankinson O. 2002. Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex. Mol Cell Biol. 22(12):4319-33. [abstract]
Braun L, Kardon T, Reisz-Porszasz ZS, Banhegyi G, Mandl J. 2001. The regulation of the induction of vascular endothelial growth factor at the onset of diabetes in spontaneously diabetic rats. Life Sci. 69(21):2533-42. [abstract]
Fukunaga BN, Probst MR, Reisz-Porszasz S, Hankinson O. 1995. Identification of functional domains of the aryl hydrocarbon receptor. J Biol Chem. 270(49):29270-8. [abstract]
Reisz-Porszasz S, Probst MR, Fukunaga BN, Hankinson O. 1994. Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT). Mol.Cell.Biol. 14(9):6075-86. [abstract]
Probst MR, Reisz-Porszasz S, Agbunag RV, Ong MS, Hankinson O. 1993. Role of the aryl hydrocarbon receptor nuclear translocator protein in aryl hydrocarbon (dioxin) receptor action. Mol.Pharmacol. 44(3):511-8.[abstract]
Reyes H, Reisz-Porszasz S, Hankinson O. 1992. Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor. Science, Vol.256:1193-1196.
Last updated 01/02/08
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