个人简介

2003-present Navari Family Professor in Life Sciences, University of Notre Dame 1997-2003 Professor, Wayne State University 1994-1997 Associate Professor, Wayne State University 1989-1994 Assistant Professor, Wayne State University 1986-1988 Postdoctoral Research Associate, Rockefeller University 1985 Ph.D. in Chemistry, University of Chicago 1981 B.S. in Chemistry, University of Southern California 1980 B.S. in Biological Sciences, University of Southern California Award: 2012 Research Achievement Award, University of Notre Dame 2007 Astellas USA Foundation Award of the American Chemical Society 2007 Elected Fellow, America Association for the Advancement of Science 1999-2001 Charles H. Gershenson Distinguished Faculty Fellow

研究领域

Biochemistry/Organic Chemistry

The Mobashery research program integrates computation, biochemistry, molecular biology, and the organic synthesis of medically important molecules. Bringing together these different disciplines is required to produce both scientific and medical advances for very difficult, but critically important clinical problems. Bacterial Resistance The study of antibiotic resistance is a central theme in the Mobashery laboratory. Mechanisms of resistance to aminoglycosides and to β-lactam antibiotics have been studied, with a focus on methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a global scourge that annually kills more people in the US (20,000 persons) than does AIDS. A multidisciplinary approach is taken towards elucidating the distinct strategies that nature has devised to counter the use of antibiotics in the clinic. Significant work has also been directed towards the bacterial cell wall. The cell wall is a structure that encases the entire organism, and it is critically important for its survival. Despite having been known to exist for the past 50 years, the structure and biochemical properties of the bacterial cell wall are being elucidated only recently, largely because of its size and diversity of structure. Mobashery’s program studies the process of biosynthesis and degradation of the cell wall. Diseases of the Extracellular Matrix The Mobashery laboratory is also interested in diseases of the extracellular matrix (ECM). The ECM is an environment that surrounds every cell in higher organisms, including humans. There are many proteins and carbohydrates within this environment, whose homeostasis is highly regulated. When these regulatory processes break down, many disparate diseases ensue. The Mobashery lab investigates how these diseases develop and progress, and develops novel therapeutics for their intervention. The diseases of matrix of interest in the Mobashery lab include cancer, diabetes and stroke. Cancer metastasis is the process that allows cancer to spread in the body, and metastatic cancer is often quickly fatal, with fatality rates near 90%. The Mobashery lab has developed molecules that prevent cancer metastasis, which they have documented in animal models for lymphoma, lung, and prostate cancers. Diabetics suffer from the lack of ability to heal their frequent skin lesions, and the infection of these lesions causes significant morbidity. The Mobashery lab has discovered molecules that accelerate wound healing in diabetic mice, with obvious clinical potential. Stroke affects 800,000 Americans annually, of whom 560,000 survive the acute episode but suffer lasting physical and mental impairment. Mobashery has designed novel therapeutics and he has documented in animal models of stroke that these drugs can rescue 50-60% of the brain cells that would otherwise die.

近期论文

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Xiao, Q.B.; Vakulenko, S.; Chang, M.; Mobashery, S. "Mutations in mmpL and in the Cell Wall Stress Stimulon Contribute to Resistance to Oxadiazole Antibiotics in Methicillin-Resistant Staphylococcus aureus." Antimicrob. Agents Ch. 2014, 58 (10), 5841-5847. Fisher, J.F.; Mobashery, S. "The sentinel role of peptidoglycan recycling in the beta-lactam resistance of the Gram-negative Enterobacteriaceae and Pseudomonas aeruginosa." Bioorg. Chem. 2014, 56, 41-48. Fishovitz, J.; Rojas-Altuve, A.; Otero, L.H.; Dawley, M.; Carrasco-Lopez, C.; Chang, M.; Hermoso, J.A.; Mobashery, S. "Disruption of Allosteric Response as an Unprecedented Mechanism of Resistance to Antibiotics." J. Am. Chem. Soc. 2014, 136 (28), 9814-9817. Blazquez, B.; Llarrull, L.I.; Luque-Ortega, J.R.; Alfonso, C.; Boggess, B.; Mobashery, S. "Regulation of the Expression of the beta-Lactam Antibiotic-Resistance Determinants in Methicillin-Resistant Staphylococcus aureus (MRSA)." Biochemistry 2014, 53 (10), 1548-1550. O'Daniel, P.I.; Peng, Z.H.; Pi, H.L.; Testero, S.A.; Ding, D.R.; Spink, E.; Leemans, E.; Boudreau, M.A.; Yamaguchi, T.; Schroeder, V.A.; Wolter, W.R.; Llarrull, L.I.; Song, W.; Lastochkin, E.; Kumarasiri, M.; Antunes, N.T.; Espahbodi, M.; Lichtenwalter, K.; Suckow, M.A.; Vakulenko, S.; Mobashery, S.; Chang, M. "Discovery of a New Class of Non-beta-lactam Inhibitors of Penicillin-Binding Proteins with Gram-Positive Antibacterial Activity." J. Am. Chem. Soc. 2014, 136 (9), 3664-3672. Gooyit, M.; Peng, Z.H.; Wolter, W.R.; Pi, H.L.; Ding, D.R.; Hesek, D.; Lee, M.; Boggess, B.; Champion, M.M.; Suckow, M.A.; Mobashery, S.; Chang, M. "A Chemical Biological Strategy to Facilitate Diabetic Wound Healing." ACS Chem. Biol. 2014, 9 (1), 105-110.