James B. Bassingthwaighte

Professor

jbb2@uw.edu
Phone: (206)685-2012
Office: Foege N510A

james_bassingthwaighte_candid

Lab Website
How I am inventing the future of medicine

Biology and Medicine are in transition from being observationally based, where predictions or treatments were empirical, into quantitative and analytical sciences where prediction and therapy are ever more based on mathematically structured systems that aid insight and guide therapeutic options. My group’s research and our open-source modeling database (http://www.physiome.org) contribute to the advancement of modeling in human biology and to practical applications in clinical medicine.
Research Interests

Cardiovascular mass transport
Cardiac metabolism
Simulation
PET imaging
Fractal physiology
Physiome project
Large scale systems modeling and analysis
Research Description

Understanding the relationships among different cell types within an organ requires integration of observations at the subcellular level, and on cells, organs, and the whole organism. In my laboratory the main focus is on the heart, but we also study liver, lung, and skeletal muscle. One program concerns the kinetics of energy metabolism, ATP, and adenosine and its metabolic products in endothelial and muscle cells. At times of stress, such as during oxygen deprivation or low flow, ATP is broken down, and adenosine concentration rises dramatically, causing vasodilation. We use multiple radioactive tracers simultaneously to measure reactions of adenosine and its metabolites and to determine their rates of transport across membranes. Models describe the kinetics in a precise way, allowing us to understand the regulation.

A second program concerns the spatial distribution of blood flow in the heart and its temporal fluctuation. Obstruction of large coronary arteries is partially compensated for by vasodilation in smaller arterioles. Fractal statistics are useful for characterizing the spatial variation in flow; branching of the vascular tree is fractal. Chaotic dynamics of arterial diameters appear due to cellular and biochemical cycling.

A third program, using PET imaging, allows us to appraise cellular metabolism in vivo and study regional myocardial blood flows and metabolism together. Tracers labeled with positrons are injected to give sequences of images. The regional concentrations change with time and the data are then analyzed via models for endothelial cell and cardiac cell metabolism.

A National Simulation Resource Facility for Circulatory Mass Transport and Exchange supports the modeling analyses. We develop models and numerical techniques and new methods for optimizing the parameters of model solutions to fit data from PET images or other laboratory studies. The long range goal is to provide clinical cardiologists with tools to link various aspects of cardiac physiology and disordered functions.

Dr. Bassingthwaighte is the originator of the Human Physiome Project, a large-scale international program for developing databasing and biological systems modeling for understanding genomic and pharmaceutic effects on human physiology. His program is highly collaborative, involving co-investigators at a dozen U.S. universities, several in Europe, and in 14 departments at the University of Washington. Some of these are involved in the Physiome Project, in particular the Cardiome Project. The Cardiome Project, to define a functional heart in mathematical terms, extends from the biochemistry and the signalling, to the mechanics and energetics of the three-dimensional heart.

Education

Ph.D. (Physiology), Mayo Graduate School of Medicine / University of Minnesota, 1964
M.D. University of Toronto, 1955
B.A. Honour Science (Physiology and Biochemistry), U of Toronto, 1951
Postdoc Information

Internship, Toronto General Hospital, 1955-6;
General Practice, Sudbury and Matheson, Ontario, 1956-57.
Clinical Cardiology Training, Post-graduate Medical School of London and Mayo Clinic, 1957-61.
Awards and Honors

2009 Fellow, International Federation of edical and Biological Engineering
2000 Election to the National Academy of Engineering
1999 Distinguished Service Award, Biomedical Engineering Society
1999 Edmund Hustinx Professorship, University of Maastricht, The Netherlands
1996 Oxford Lecturer (International Society of Magnetic Resonance in Medicine)
1995 Landis Award (Microcirculatory Society)
1993-2000 Editor-in-Chief, Annal of Biomedical Engineering
1993 Burlington Award for Outstanding Research in Engineering, University of Washington
1990-1991 President Micorcirculatory Society
1986-1999 Chair, Comm on Bioeng in Physiology of the International Union of Physiological Sciences
1986 Alza Award of the Biomedical Engineering Society
1978-1986 USA National Comm for International Union of Physiology Science (IUPS, Chair 1983-1986)
1979 Louis and Artur Lucian Award, McGill University
1977-78 Presient Biomedical Engineering Society
1964-1974 Research Career Development Award (NHLBI)
1964 Mayo Alumni Research (Balfour) Award
UW Bioengineering Courses Taught

BIOEN 550 Quantitative Physiology and Transport
BIOEN 599 Fractal Physiology
Selected Publications

Jardine B and Bassingthwaighte JB. Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation. Am J Physiol Lung Cell Mol Physiol 305: L42-L55, 2013.

Alessio AM, Bassingthwaighte JB, Glenny RA, Caldwell JH. Validation of an axially-distributed model for quantification of myocardial blood using 13N-ammonia PET. J Nuc.Cardiol. 20:64-75, 2013.

Bassingthwaighte JB and Chinn TM. Re-examining Michaelis-Menten enzyme kinetics for xanthine oxidase. Adv Physiol Educ 37: 37-48, 2013.

Bassingthwaighte JB, Butterworth E, Jardine B, and Raymond G. Compartmental modeling in the analysis of biological systems. In “Computational Toxicology: Volume 1″, edited by Brad Reisfeld and Arthur N Mayeno. Methods in Molecular Biology 929: 391-438, 2012.

Bassingthwaighte JB, Beard DA, Carlson BE, Dash RK, and Vinnakota K. Modeling to link regional myocardial work, metabolism and blood flows. Ann Biomed Eng 40: 2379-2398, 2012.

Bassingthwaighte JB, Noble D, and Hunter PJ. The Cardiac Physiome: perspectives for the future. Experimental Physiology 94.5: 597-605, 2009.

Kellen MR and Bassingthwaighte JB. Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285: H1317-H1331, 2003.

Bassingthwaighte JB. The macro-ethics of genomics to health: The Physiome Project. Comptes Rendus Biologies de l’Academie des sciences francaise 326: 1105-1110, 2003.

Beard, D.A., and J.B. Bassingthwaighte. Advection and diffusion of substances in biological tissues with complex vascular networks. Ann. Biomed. Eng. 28:253-268, 2000.

Beard D.A., and J.B. Bassingthwaighte. The fractal nature of myocardial blood flow emerges from a whole-organ model of arterial network. J. Vasc. Res. 37:282-296, 2000.

Bassingthwaighte JB. Strategies for the Physiome Project. Ann Biomed Eng 28: 1043-1058, 2000.

Bassingthwaighte, J.B., and Z. Li. The Cardiome Project: An integrated view of cardiac metabolism and regional mechanical function. Adv. Exp. Med. Biol. 471: 541-553, 1999.

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