Daniel L. Cook, MD, PhD
Department of Physiology & Biophysics
Department of Biological Structure
University of Washington
Knowledge representation and causal reasoning. Perceiving a need for more
powerful languages for describing and analyzing biological systems, Dr. Cook
developed BioD, a biological description language as a computational tool for qualitatively predicting
cause/effect relationships in biological causal networks. He is now extending and generalizing BioD's
representational principles as a Physiological Reference Ontology in collaboration with the developers of the
Foundational Model of Anatomy. This work, a critical part of the DARPA-funded Virtual Soldier Project, has
garnered national and international recognition for its comprehensive and highly-principled approach to
biological knowledge representation. Dr. Cook continues to lead the development of an Ontology of Physics
in Biology that will lay the theoretical foundations for practical applications that will be capable of
generating complex computer code for multiscale biosimulations.
Biological systems analysis.
While maintaining a collaborative interest in the control of insulin secretion
and diabetes, Dr. Cook has pursued a long term interest in analyzing complex biological systems. He has
published simulation studies in such disparate fields as beta-cell electrophysiology, detoxification enzyme
kinetics, and stochastic gene expression and, most recently, a novel analysis of synaptic depression in auditory signal processing (Nature, 2003).
Insulin secretion and diabetes.
Dr. Cook published his thesis work on the membrane electrical activity of insulin-secreting beta cells in Nature (1980) and subsequently published the first patch-clamp studies of
beta cell ion channels (both in Nature, 1984). These studies included the seminal identification of ATP
-sensitive potassium channels as the "missing links" coupling beta cell energy metabolism to cellular
calcium uptake and insulin secretion. Subsequent collaborative studies (The Lancet, 1985) identified ATP
-sensitive potassium channels as receptors for the widely-used sulphonylurea class of oral anti-diabetic agents.
University of Michigan, Ann Arbor, MI
University of Washington, Seattle, WA
University of Washington, Seattle, WA
University of Washington, Seattle, WA
Medical Scientist Pathway
Physiology & Biophysics
Knowledge representation and causal reasoning
Rosse, C., A. Kumar, et al. (2005). A Strategy for Improving and Integrating Biomedical Ontologies.
Proceedings, American Medical Informatics Association 2005 Symposium.
Cook, D. L., J. L. Mejino, et al. (2004). Evolution of a Foundational Model of Physiology: symbolic
representation for functional bioinformatics. Medinfo 11(Pt 1): 336-40.
Cook, D. L., J. L. V. Mejino, and Rosse, C.: The Foundational Model of Anatomy: a template for the
symbolic representation of multi-scale physiological function. Proceedings of the 25th Annual International
Conference of the IEEE Engineering in Medicine and biology Society (2004, in press).
Cook, D.L., Farley, J.F., and Tapscott, S.J.: A basis for a visual language to describe, archive and
analyze functional models of complex biological systems. Genome Biology, 2001.
Biological systems analysis
Cook, D. L., P. C. Schwindt, et al. Synaptic depression in the localization of sound. Nature 421: 86
Atkins, W.A., Lu, W.D. and Cook, D.L.: Is there a toxicological advantage for non-hyperbolic kinetics in
cytochrome P450 catalysis? Functional allostery from "distributive catalysis". J Biol Chem 277:33258-66, 2002.
Cook, D.L., Gerber, A.N. and Tapscott, S.J.: Modeling stochastic gene expression: Implications for
haploinsufficiency. Proc Natl Acad Sci U S A. 95:15641-6, 1998.
Cook, D.L. and Atkins, W.A.: Enhanced detoxification due to distributive catalysis and toxic thresholds: A
kinetic analysis. [New Concepts in Biochemistry] Biochemistry 36:10801-10806, 1997.
Chay, T.R. and Cook, D.L.: Endogenous bursting pattern in excitable cells. Mathematical Biosciences
Cook, D.L., Satin, L.S., Ashford, M.L.J., and Hales, C.N.: ATP-sensitive K-channels in pancreatic B-cells:
The "spare channel" hypothesis. Diabetes 37:495-498, 1988.
insulin secretion and ATP-sensitive potassium channels
Sweet, I. R., D. L. Cook, et al. Regulation of ATP/ADP in pancreatic islets. Diabetes 53(2): 401-9, 2004.
Cook, D. L. and Bryan, J.: ATP-sensitive potassium channels and disease. Trends in Pharmacological
Sciences 19(12): 477-8, 1998.
Hopkins, W. F., Fatherazi, S., Peter-Riesch, B., Corkey, B. E. and Cook, D. L.: Two sites for adenine
-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic ß-cells and HIT cells. Journal of Membrane Biology 129:287-295, 1992.
Cook, D.L., Satin, L.S. and Hopkins, W.F.: Pancreatic B-cells are bursting, but how? Trends in
Neurosciences 14:411-414, 1991.
Fatherazi, S. and Cook, D.L.: Specificity of tetraethylammonium and quinine for three K channels in insulin
-secreting cells. Journal of Membrane Biology 120:105-114, 1991.
Hopkins, W.F., Satin, L.S., and Cook. D.L.: Inactivation kinetics and pharmacology distinguish two calcium
currents in mouse pancreatic B-cells. Journal of Membrane Biology 119:229-239, 1991.
Hopkins, W.F., Fatherazi, S. and Cook, D.L.: The oral hypoglycemic agent, U-56324, inhibits the activity of
ATP-sensitive potassium channels in cell-free membrane patches from cultured mouse pancreatic B-cells. FEBS Letters 277:101-104, 1990.
Satin, L.S. and Cook, D.L.: Calcium current inactivation in insulin-secretion cells is mediated by calcium
influx and membrane depolarization. Pflügers Archiv, 414:1-10, 1989.
Satin, L.S., Hopkins, W.F., Fatherazi, S., and Cook, D.L.: Expression of a rapid, low voltage threshold K
current in insulin-secreting cells is dependent on intracellular calcium buffering. Journal of Membrane Biology 112:213-222, 1989.
Cook, D.L. and Ikeuchi, M.: Tolbutamide as mimic of glucose on ß-cell electrical activity: ATP-sensitive K
channels as common pathway for both stimuli. Diabetes 38:416-421, 1989.
Satin, L.S. and Cook, D.L.: Evidence for two calcium currents in insulin secreting cells. Pflügers Archiv
Satin, L.S. and Cook, D.L.: Voltage-gated Ca++ current in pancreatic B-cells. Pflügers Archiv 404:385-387,
Sturgess, N.C., Ashford, M.A.J., Cook, D.L. and Hales, C.N.: The sulfonylurea receptor may be an
ATP sensitive potassium channel. Lancet 11:474-475, 1985.
Cook, D.L. and Hales, C.N.: Intracellular adenosine triphosphate directly blocks K+ channels in
pancreatic B-cells. Nature 311:37l-372, 1984.
Cook, D.L., Ikeuchi, M. and Fujimoto, W.Y.: Decreasing pH inhibits Ca++ activated K+ channels in
pancreatic B-cells. Nature 311:369-37l, 1984.
Ikeuchi, M., Fujimoto, W.Y. and Cook, D.L.: Rat islet cells have glucose-dependent periodic electrical
activity. Hormone and Metabolic Research 16:125-127, 1984.
Cook, D.L.: Isolated islets of Langerhans have slow oscillations of electrical activity. Metabolism 32:681
Cook, D.L. and Perara, E.:Islet electrical pacemaker response to alpha-adrenergic stimulation Diabetes
Cook, D.L., Crill, W.E. and Porte, D., Jr.: Glucose and acetylcholine have different effects on the plateau
pacemaker of pancreatic islet cells. Diabetes 30:550-561, 1981.
Cook, D.L., Crill, W.E. and Porte, D., Jr.: Voltage dependence of rhythmic plateau potentials of pancreatic
islet cells. American J. of Physiology 240:E290-E296, 1981.
Cook, D.L., Crill, W.E. and Porte, D., Jr.: Plateau potentials in pancreatic islet cells are voltage
-dependent action potentials. Nature 286:404-405, 1980.
Sweet, I. R., D. L. Cook, et al. Systematic screening of potential beta-cell imaging agents. Biochem
Biophys Res Commun 314(4): 976-83, 2004.
Sweet, I. R., D. L. Cook, et al. Dynamic perifusion to maintain and assess isolated pancreatic islets.
Diabetes Technol Ther 4(1): 67-76, 2002.
Pfeifer, M.A., Weinberg, C.R., Cook, D.L., Reenan, A., Halar, E., Halter, J.B., LaCava, E.C., and Porte, D., Jr
.: Correlations among autonomic, sensory, and motor-neural function tests in untreated noninsulin
-dependent diabetes. Diabetes Care 8:576-584, 1985.
Pfeifer, M.A., Weinberg, C.R., Cook, D.L., Reenan, A., Halter, J.B., Ensinck, J.W., Porte, D., Jr.: Autonomic
neural dysfunction in recently diagnosed diabetic subjects. Diabetes Care 7:447, 1984.
Pfeifer, M.A., Weinberg, C.R., Cook, D.L., Best, J.D., Reenan, A. and Halter, J.B.: Differential changes of
autonomic nervous system function with age in man. American Journal of Medicine 75:249-258, 1983.
Pfeifer, M.A., Cook, D.L., Brodsky, J., Tice, D., Reenan, A., Swedine, S., Halter, J.B. and Porte, D., Jr.:
Quantitative evaluation of cardiac parasympathetic activity in normal and diabetic man. Diabetes 31:339-345, 1982.
O'Leary, M.R., Cram, J., Cumming, C., Cook, D.L. and Walker, R.D.: Neuropsychological status, depression
and autonomic deficit in male alcoholics. Research Communication in Substance Abuse 1:211-220, 1980.
Textbooks and Symposia
Cook, D. L. and Hopkins, W. F.: Generation and control of bursting electrical activity in pancreatic ß-cells.
In: Pacemaker Activity and Intercellular Communication, J. Huizinga (ed.), CRC Press, Boca Raton FL, 1995.
Cook, D.L. and Taborsky, G.J., Jr.: B-cell function and insulin secretion. In: Diabetes Mellitus, Theory and
Practice, 4th Edition, D. Porte, Jr. and H. Rifkin (eds.), Elsevier Science Publ., New York, pp. 89-103, 1990; 5th Edition, 1995
Cook, D.L.: The cellular biology of the endocrine system: an overview. In: Textbook of Physiology, 21st
Edition, H.D. Patton, et al. (eds.), W.B. Saunders, Philadelphia, pp. 139-159, 1989.
Cook, D.L.: Tolbutamide control of B-cell membrane potential and electrical activity: a role for ATP
-sensitive channels? In: Diabetes, 1988, R. Larkins, et al. (eds.), Elsevier Science Publ., New York, pp.455-458, 1988.
Satin, L.S and Cook, D.L.: Voltage-gated Ca current in pancreatic B-cells. In: Biophysics of the Pancreatic
B-Cell, I. Atwater, et al. (eds.), Plenum, New York, pp. 189-193, 1986.
Ashford, M.L.J., Sturgess, N.C., Cook, D.L. and Hales, C.N.: K-channels in an insulin secreting cell line:
effects of ATP and sulphonylureas. In: Biophysics of the Pancreatic B-Cell, I. Atwater, et al. (eds.), Plenum, New York, pp. 69-76, 1986.
Cook, D.L., Hales, C.N., and Satin, L.S.: Glucose suppresses ATP inhibited K-channels in pancreatic B-cells.
In: Biophysics of the Pancreatic B-Cell, I. Atwater, et al. (eds.), Plenum, New York, pp. 63-67, 1986.
Cook, D.L.: Electrical pacemaker mechanisms of pancreatic islet cells. Federation Proceedings 43:2368