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Scientific Experience (kurt.bohren@salusenterprises.com)
Academic and industrial scientist with proven record (39 peer-reviewed publications gene-rating over 2400 citations (average 61/paper, h-index of 23, ISI Web of Knowledge). Complete list: PubMed
Professional Experience
Metabolon, Inc. (Research Triangle Park, North Carolina)
Senior Study Director (2011)
- Responsible for analyzing huge metabolic datasets (GC/MS and LC/MS/MS) across many species and diseases, pathway interpretations, final reports and presentations to academic clients and clients from private companies (biotech & pharma).
Children’s Nutrition Research Center 2010-2011 (Baylor College of Medicine. Houston, TX)
Assistant Professor (part-time).
- Reorganized a vacant laboratory, brought old instruments to life, and carried out protein expression experiments related to bone homeostasis.
Immunodiagnostic Systems, Inc. UK-headquartered Company that develops, manufactures, and markets widest range of biomarker diagnostic test kits.
Scientific Liaison (2008 – 2009), contracted as independent Scientific Consultant in 2010
- Interacted with scientists working in academic and industry, nationwide. Communicated information regarding pre-clinical and clinical applications of biomarker assays for dynamic monitoring of bone and cartilage during disease (osteoporosis, osteoarthritis, rheumatoid arthritis) and therapy. Identified, diagnosed, and resolved application issues.
- Collaborated and built relationships with key thought leaders in field of bone and cartilage research.
- Authored internal papers for emerging business opportunities stemming from research published in scientific journals.
- Co-authored position paper in peer-reviewed scientific journal (Biomarkers, published in May 2010), and corporate newsletter for clients.
Baylor College of Medicine, Houston, TX. Premier academic health science center, known worldwide for excellence in education, research, and patient care.
Assistant Professor, Dept. of Pediatrics, Molecular Diabetes and Metabolism Section (1990-2001)(2002 – 2008)
- Planned and managed research projects concerning diabetic complications at the molecular level.
- Supervised team of technicians and post-doctoral fellows, and conducted many experiments hands-on.
- Developed genetically-engineered mice (gene knockouts and point mutations).
- Conducted and evaluated experiments involving complex instrumentation and computer analysis.
- Developed kinetic and analytical assays. Performed kinetic model evaluation, and statistical analysis.
- Built and shared biochemical and molecular biology expertise in recombinant protein production (for crystallization, kinetic and NMR experiments) and protein engineering based on structure/function and protein crystallization studies (deposited 9 different structures in NCBI data base). Conducted enzyme kinetic studies that included steady-state and pre-steady state kinetics, isotope effects, and tight-binding.
- Presented important findings at international conferences.
- Wrote grant applications, and co-authored papers (38) that were published in peer-reviewed high-impact scientific journals (average citations: 60/paper).
- Coached medical students to facilitate integrated problem solving.
Pharmaceutical Discovery, Lexicon Genetics, The Woodlands, TX. Biopharmaceutical Company focused on drug discovery and development. Company was pioneer of proprietary gene knockout technology. Transformed into Pharmaceutical Company in 2001.
Senior Scientist (2001 – 2002)
- Oversaw assay development for high-throughput screening of potential new inhibitory molecular entities in the Pharmaceutical Discovery group. Worked in the laboratory, and carried out many experiments hands-on.
- Created vectors for recombinant enzyme production, evaluated phenotypes of mice with a particular null gene for potential new drug targets, gathered data, and acquired instruments to facilitate program success.
Education
Universität Bern, Switzerland
Doctor of Philosophy: Biochemistry
Master of Science: Chemistry
University of Houston, Houston, TX
Master of Education, Concentration: Medical Education
Gymnasium Bern Kirchenfeld, Switzerland
Bachelor of Arts: Classical Education
HIghlights of Scientific Accomplishments
- First to clone human aldose and human aldehyde reductase, and established aldo-keto reductase superfamily of enzymes. Predicted that many more enzymes and proteins would be found. Today 100+ proteins are described in that superfamily.
- Led project to characterize human aldose reductase from initial isolation, cloning, expression, crystallization, to high resolution (1.8 Å) X-ray structure in less than 4 years, competing with NASA (National Aeronautics and Space Administration), which was unable to obtain high-quality crystal of this protein in space during a Columbia shuttle mission in 1992. This β8α8 structure established a new NADPH-binding motif for oxidoreductases, and was the first structure ever solved for the aldo-keto reductase superfamily.
- Demonstrated, for first time, how enzyme uses a tyrosine residue that can be replaced by a water molecule in a Tyr- to-His mutant as proton donor in the reduction reaction of an aldehyde substrate. In collaboration with scientists at Brandeis, Scripps, and the Mayo Foundation, determined kinetic and inhibition mechanisms of this enzyme based on microscopic rate constants, direct binding studies, and ligand exchanges in protein crystals. Established a new standard of excellence in aldo-keto reductase field.
- Spearheaded development of a bio-engineered mouse model for diabetic complications. In this model the aldose reductase gene was altered with 2-point mutations to produce a more efficient mouse aldose reductase enzyme to reflect properties of the human enzyme. The necessary point mutations were identified by interpretation of primary and tertiary structures and subsequent kinetic analysis of mutant enzymes. Developed another mouse model with mild ascorbic acid deficiency and a phenotype resembling human osteoporosis.
- Crystallized several proteins (aldose reductase, aldehyde reductase, carbonyl reductase) and mutants of human aldose reductase, the latest being the apoenzyme that verifies a hypothesized isomerization with respect to the holoenzyme by a loop movement of 17 angstroms. Validated a 10-year old “loop movement” theory stemming from interpretation of slow and rate-limiting exchange of NADP+ with NADPH in the catalytic mechanism.
- Selected as 1st enzymologist for Lexicon Genetics. Directed charge of assay development.
- First to perform functional studies on a new SUMO protein and association of single nucleotide polymorphism in the open reading frame of SUMO4 gene with type 1 diabetes. Generated rapid response from colleagues worldwide, confirming association with type I diabetes in Asian populations, but not in white populations where association data has provided conflicting, but generally negative results.
Honors
Career Development Award, Juvenile Diabetes Foundation International
Harry B. and Aileen B. Gordon Foundation Fellowship, Baylor College of Medicine
Patent
US Patent 06630324
Characterized 2 genes (human aldose reductase and human aldehyde reductase) involved in diabetic complications in terms of simple intron/exon boundaries as well as exhaustive studies of their promoter activities). Research led to identification of hypertonicity response element in aldose reductase gene promoter and discovery of alternative splicing of aldehyde reductase mRNA. Awarded patent for a bidirectional promoter.
Selected Publications
Average citations per item: 61 with an h index of 22 (ISI Web of Knowledgesm). Six most cited ones:
The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. Bohren KM, Bullock B, Wermuth B, Gabbay KH., J Biol Chem. 1989 Jun. (349 citations ). Abstract
An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA., Science. 1992 Jul. (343 citations ). Abstract
A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. Bohren KM, Nadkarni V, Song JH, Gabbay KH, Owerbach D., J Biol Chem. 2004 Jun. (209 citations). Abstract
Tyrosine-48 is the proton donor and histidine-110 directs substrate stereochemical selectivity in the reduction reaction of human aldose reductase: enzyme kinetics and crystal structure of the Y48H mutant enzyme. Bohren KM, Grimshaw CE, Lai CJ, Harrison DH, Ringe D, Petsko GA, Gabbay KH., Biochemistry. 1994 Mar. (144 citations). Abstract
Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and amino acid sequence of the encoded protein. Wermuth B, Bohren KM, Heinemann G, von Wartburg JP, Gabbay KH., J Biol Chem. 1988 Nov (135 citations). Abstract
An anion binding site in human aldose reductase: mechanistic implications for the binding of citrate, cacodylate, and glucose 6-phosphate. Harrison DH, Bohren KM, Ringe D, Petsko GA, Gabbay KH., Biochemistry. 1994 Mar. (129 citations). Abstract
Technical Expertise
- Metabolomics: Interpretation and analysis of complex heat maps across species and diseases.
- Purification (chromatography: SEC (gel filtration), ion exchange, affinity, HPLC; for kinetics, crystallization or NMR experiments, antibody production), protein chemistry (proteomics), crystallization, and protein engineering based on function/atomic structure using common molecular biology tools.
- Enzymology: broad knowledge of enzyme kinetics including steady-state and pre-steady state kinetics, isotope effects, and tight-binding, both in terms of conducting and evaluating experiments using computer analysis and modeling for kinetic model evaluation, and genetically-engineered mice to change glucose metabolism.
- Development of enzyme assays and proficient with various molecular biology tools that include cloning, vector construction, library screening, PCR, promoter characterization, binding and gelshift assays.
- Computer Skills: MS Office (up to 2007)., LIMS, Array Studi, essential networking, computational biology, data mining.
- Programming: HP Chemstation, scripting in Sigmaplot and Biokin’s Dynafit, and HTML.
- GC/MS (Gas chromatography-mass spectroscopy) process, UV/Vis and fluorescenc spectroscopy.
- Statistical analysis using Systat (parametric, non-parametric, ANOVA, Kruskal-Wallis, etc.).
Professional Affiliations
- Adjunct Faculty Member, Baylor College of Medicine, Houston , Texas, USA
- American Chemical Society
- American Association for the Advancement of Science
- Endocrine Society
- American Society for Bone and Mineral Research
- Osteoarthritis Research Society International
- National Science Teacher Association
- The New York Academy of Sciences
Foreign Language Skills
Proficient in German, Swiss German, and French
Biographical
Dual citizenship of Switzerland and the USA
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