Literature DB >> 31953248

So many roads traveled: A career in science and administration.

James R Halpert1.   

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.
© 2020 Halpert.

Entities:  

Keywords:  CYP2B enzymes; chemical biology; cytochrome P450; pharmacology; structure-function; toxicology

Mesh:

Substances:

Year:  2020        PMID: 31953248      PMCID: PMC6970931          DOI: 10.1074/jbc.X119.012206

Source DB:  PubMed          Journal:  J Biol Chem        ISSN: 0021-9258            Impact factor:   5.157


  51 in total

1.  Identification of three key residues in substrate recognition site 5 of human cytochrome P450 3A4 by cassette and site-directed mutagenesis.

Authors:  Y A He; Y Q He; G D Szklarz; J R Halpert
Journal:  Biochemistry       Date:  1997-07-22       Impact factor: 3.162

2.  Oxygen affinity in red cells: inability to show membrane-bound 2,3-diphosphoglycerate.

Authors:  E G Brann; D J Newman; F A Oski
Journal:  Science       Date:  1973-02-09       Impact factor: 47.728

3.  Directed evolution of mammalian cytochrome P450 2B1: mutations outside of the active site enhance the metabolism of several substrates, including the anticancer prodrugs cyclophosphamide and ifosfamide.

Authors:  Santosh Kumar; Chong S Chen; David J Waxman; James R Halpert
Journal:  J Biol Chem       Date:  2005-03-17       Impact factor: 5.157

4.  Site-directed mutagenesis as a tool for molecular modeling of cytochrome P450 2B1.

Authors:  G D Szklarz; Y A He; J R Halpert
Journal:  Biochemistry       Date:  1995-11-07       Impact factor: 3.162

5.  Potent mechanism-based inactivation of cytochrome P450 2B4 by 9-ethynylphenanthrene: implications for allosteric modulation of cytochrome P450 catalysis.

Authors:  Haoming Zhang; Sean C Gay; Manish Shah; Maryam Foroozesh; Jiawang Liu; Yoichi Osawa; Qinghai Zhang; C David Stout; James R Halpert; Paul F Hollenberg
Journal:  Biochemistry       Date:  2013-01-04       Impact factor: 3.162

6.  Peripheral ligand-binding site in cytochrome P450 3A4 located with fluorescence resonance energy transfer (FRET).

Authors:  Dmitri R Davydov; Jessica A O Rumfeldt; Elena V Sineva; Harshica Fernando; Nadezhda Y Davydova; James R Halpert
Journal:  J Biol Chem       Date:  2011-12-22       Impact factor: 5.157

7.  Taipoxin, an extremely potent presynaptic neurotoxin from the venom of the australian snake taipan (Oxyuranus s. scutellatus). Isolation, characterization, quaternary structure and pharmacological properties.

Authors:  J Fohlman; D Eaker; E Karlsoon; S Thesleff
Journal:  Eur J Biochem       Date:  1976-09-15

8.  An open conformation of mammalian cytochrome P450 2B4 at 1.6-A resolution.

Authors:  Emily E Scott; You Ai He; Michael R Wester; Mark A White; Christopher C Chin; James R Halpert; Eric F Johnson; C David Stout
Journal:  Proc Natl Acad Sci U S A       Date:  2003-10-16       Impact factor: 11.205

9.  Suicide inactivation of rat liver cytochrome P-450 by chloramphenicol in vivo and in vitro.

Authors:  J Halpert; B Näslund; I Betnér
Journal:  Mol Pharmacol       Date:  1983-03       Impact factor: 4.436

10.  Structure-Function Analysis of Mammalian CYP2B Enzymes Using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism.

Authors:  Manish B Shah; Jingbao Liu; Lu Huo; Qinghai Zhang; M Denise Dearing; P Ross Wilderman; Grazyna D Szklarz; C David Stout; James R Halpert
Journal:  Mol Pharmacol       Date:  2016-01-29       Impact factor: 4.436

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