Abstract
I have traveled many roads during my career. After spending my first 19 years in Los Angeles, I became somewhat of an academic nomad, studying and/or working in six universities in the United States and three in Sweden. In chronological order, I have a B.A. in Scandinavian languages and literature from UCLA, a Ph.D. in biochemistry from Uppsala University, and an M.S. in toxicology from the Karolinska Institute. I have been in schools of natural science, pharmacy, and medicine and have worked in multiple basic science departments and one clinical department. I have served as a research-track and tenured faculty member, department chair, associate dean, and dean. My research has spanned toxinology, biochemistry, toxicology, and pharmacology. Through all the moves, I have gained much and lost some. For the past 40 years, my interest has been cytochrome P450 structure-function and structure-activity relationships. My lab has focused on CYP2B enzymes using X-ray crystallography, site-directed mutagenesis, deuterium-exchange MS, isothermal titration calorimetry, and computational methods in conjunction with a variety of functional assays. This comprehensive approach has enabled detailed understanding of the structural basis of the remarkable substrate promiscuity of CYP2B enzymes. We also have investigated the mechanisms of CYP3A4 allostery using biophysical and advanced spectroscopic techniques, and discovered a pivotal role of P450-P450 interactions and of multiple-ligand binding. A major goal of this article is to provide lessons that may be useful to scientists in the early and middle stages of their careers and those more senior scientists contemplating an administrative move.
Highlights
The title of this article derives from my love for the blues and admiration for the guitarist Otis Rush
Eight years later, when separating different rat liver P450s from each other, I realized that my successful final purification step for epoxide hydrolase was the result of the P450 denaturing on the column during the prolonged chromatography
That was the hardest thing I have ever done.). It is striking how little was known about P450 enzymes when I started at Vanderbilt (Fig. 3)
Summary
In order for me to attend better schools, we moved 10 miles to Sherman Oaks. my father was a well-respected journalist, and he later became one of the pioneers in television news and a household name to literally millions of Los Angeles residents. As a lab helper for our junior high school science teacher, Mrs Munson, I had a small project to determine the normality of an HCl solution by titrating with NaOH in the presence of the pH-sensitive dye phenolphthalein It sounded so easy, yet I could never get the. REFLECTIONS: So many roads traveled same result twice It was not until almost 60 years later when writing this article that I discovered from the internet that the key is to recognize the right end point, which is a faint pink color that persists for 30 seconds. This episode yielded the first two take-home lessons of this Reflections article.
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