So many roads traveled: A career in science and administration

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.

Four Decades of Cytochrome P450 2B Research: From Protein Adducts to Protein Structures and Beyond

“…However, no such residues had been identified; their role in species and individual differences in substrate metabolism was completely unknown, and solving a mammalian P450 X-ray crystal structure was a mere fantasy. Through the efforts of the individuals featured in this article and many others, our group achieved an atomic-level understanding of ligand binding and substrate turnover by CYP2B enzymes (Shah et al, 2012;Halpert, 2020). We also revealed the importance of enzyme plasticity and its role in the thermodynamics of ligand binding (Shah et al, 2015), as well as the role of halogen-π bonds in ligand recognition (Shah et al, 2017), which were totally unanticipated before structures became available.…”