In this video Dr. Steve Sligar gives an overview of the Nanodisc platform and its use in drug discovery, imaging, and therapeutic delivery. This is followed by a talk by Dr. Sligar’s student, Michael Gregory, who discusses his work in androgen biosynthesis. A brief abstract relating to Michael Gregory’s work in the area: Human Cytochrome P45017A1 (CYP17) catalyzes the 17 alpha-hydroxylation of pregnenolone and progesterone as well as the subsequent 17,20 carbon-carbon lyase chemistry of its hydroxylated products. CYP17 function plays a central role in human steroid hormone biosynthesis, and its activity is absolutely essential for the formation of androgens. Thus, inhibition of CYP17 has recently been exploited in the treatment of androgen dependent malignancies. Through application of nanotechnology and biophysical tools, we have identified novel characteristics of CYP17 chemistry that may guide development of the next generation of mechanism-based inhibitors.
Dr. Stephen G. Sligar Stephen G. Sligar received his Ph.D. in Physics from the University of Illinois in 1975. Dr. Sligar served on the faculty in the Department of Molecular Biophysics and Biochemistry at Yale University and returned to the University of Illinois in 1982 where he was the I. C. Gunsalus Professor of Biochemistry. He now holds the University of Illinois Swanlund Endowed Chair and is Director of the School of Molecular and Cellular Biology. He is also a faculty member in the Department of Chemistry, the Center for Biophysics and Computational Biology and the College of Medicine. Dr. Sligar holds affiliate appointments in the Beckman Institute for Advanced Science and Technology, the Institute for Genomic Biology and The Micro and Nano Technology Laboratory on the Illinois campus. He is a Fellow of the Biophysical Society and the American Association for the Advancement of Science. Awards include a Fulbright Research Scholarship, Senior Fellowship from the Japan Society for the Promotion of Science, an NIH Merit Award and the Bert L. and Kuggie Vallee Visiting Professorship in Inorganic Chemistry at Oxford where he was a Fellow of Queens College. He is also a Fellow in the Jerome Karle Nobel Laureate World Innovation Foundation. Dr. Sligar's research is supported by grants from the National Science Foundation, the National Institutes of Health and the Human Frontiers Program. Research centers on understanding the structure and mechanistic function of metalloenzymes, membrane bound receptors and transporters as well as investigations in blood coagulation and amyloid proteins and their corresponding human disease states.
Michael Gregory After spending his adolescence in the Chicago suburbs, Michael Gregory attended DePauw University where he earned a bachelor's degree in biochemistry in 2008. Following graduation, he returned to the Chicago area and joined the R&D division of a major biopharmaceutical company where he assisted development of protein based therapies for the treatment of pulmonary disorders. In 2009, he came to the University of Illinois and is currently a biochemistry graduate student working in the laboratory of Dr. Stephen Sligar. Here he is studying the steroidogenic enzyme Cytochrome P450c17 (CYP17), which catalyzes the first committed step in androgen formation. As a result of CYP17's role as gatekeeper to androgen biosynthesis it is a front line target in the fight against castration-resistant prostate cancer, which proliferates in response to androgen receptor activation. Michael hopes to integrate knowledge gleaned from rigorous biophysical characterization of CYP17 catalysis with emerging diagnostic and nanotechnologies to encourage development of next-generation therapeutics for the treatment of androgen responsive malignancies such as castration-resistant prostate cancer.
Midwest Cancer Nanotechnology Traning Center (M-CNTC) Training the next generation of leaders who will define the new frontiers and applications of nanotechnology in cancer research It is known that more than 1.5 million Americans were diagnosed with cancer during 2010, and half a million have died (Cancer Statistics 2010, ACS). In spite of considerable effort, there has been limited success in reducing per capita deaths from cancer since 1950. This calls for a paradigm shift in the understanding, detection, and intervention of the evolution of cancer from a single cell to tumor scale.
In response to this challenge the M-CNTC has assembled a preeminent interdisciplinary team of researchers and educators across the University of Illinois and clinical collaborators in the Midwest to train the next generation of engineers, physical scientists, and biologists to address the challenge of understanding, managing, diagnosing, and treating cancer using the most recent advancements in nanotechnology.
Cellular and Molecular Mechanics and Bionanotechnology (CMMB-IGERT) Training the next generation of leaders who will define the new frontiers of cellular and molecular mechanics and bionanotechnology Critical experiments during the last decade show a fundamental link between the micro- and macro-mechanical environment (i.e., intracellular forces, local shear, gravitational force) and a variety of cell functionalities, their lineage, and phenotype. These findings pose the grand challenge: what is the underlying molecular mechanism that cells employ to transduce mechanical signals to biochemical pathways?
In response to this challenge the CMMB IGERT launched an interdisciplinary research effort with national and international collaborators.