Research interests

Homologous proteins (proteins which perform the same function) in different organisms often must function in either extreme or fluctuating environments. Work in my laboratory centers on the study of the relationships between the structure of these proteins and their ability to maintain optimal levels of function. Our primary study systems are the oxygen binding proteins hemoglobin and myoglobin of teleost fishes. Members of this group have adapted to live at both cold and warm temperature extremes. In addition, some species are able to withstand substantial fluctuations in temperature in relatively short periods of time. We utilize structural modeling and protein stability studies in conjunction with thermodynamic and kinetic data analysis to attempt to identify adaptive protein motifs and other features that affect oxygen delivery and storage in poikilothermic organisms adapted to these extreme and fluctuating environments.

Publications

• Sund, E.H., Cashon, R.E., and Palma, R.J. (1975) "Dissociation constants of 1(2-Pyridyl)-2-Alkanones" J. Chem. Eng. Data 20(4), 370.
• Sund, E.H., Cashon, R.E., and Taylor, R.L. (1980) "2-Alkyl-3-(2-Pyridyl)-Cinchoninic Acids" Texas Journal of Science 32, 93.
• Greaney, G.S., Place, A.R., Cashon, R.E., Smith, G., and Powers, D.A. (1980) "Time course of changes in enzyme activities and blood respiratory properties of killifish during long-term acclimation to hypoxia" Physiol. Zool. 53(2), 136-144.
• Van Beneden, R.J., Cashon, R.E., and Powers, D.A. (1981) "Biochemical genetics of Fundulus heteroclitus (L). III. Inheritance of isocitrate dehydrogenase (Idh-A and Idh-B), 6-phosphogluconate dehydrogenase (6-Pgdh-A) and serum esterase (Est-S) polymorphisms" Biochem. Genet. 19, 715-727.
• Cashon, R.E., Van Beneden, R.J., and Powers, D.A. (1981) "Biochemical genetics of Fundulus heteroclitus (L).IV. Spatial variation in gene frequencies of Idh-A, Idh- B, 6-Pgdh-A, and Est-S" Biochem. Genet. 19, 715-727.
• Sugihari, J., Imamura, T., Nagafuchi, S., Bonaventura, J., Bonaventura, C., and Cashon, R.E. (1985) "Hemoglobin Rahere, a human hemoglobin variant with amino-acid substitution at the 2,3-diphosphoglycerate binding site: Functional consequences of the alteration and effects of bezafibrate on the oxygen
• Alayash, A.I., Dafallah, A., Al Husayni, H., Al Ali, A.K., Al Quorain, A., Omer, A.H.S., Wilson, M.T., Bonaventura, J., and Cashon, R.E. (1986) "Glycosylated hemoglobin levels in a benign form of sickle cell anemia in Saudia Arabia" Acta
• Cashon, R.E., Bonaventura, C., Bonaventura, J., and Focesi, A. (1986) "The nicotinamide adenine dinucleotides as allosteric effectors of human hemoglobin" J. Biol. Chem.261(27), 12700- 12705.
• Powers, D.A., Ropson, I., Brown, D.C., Van Beneden, R.J., Cashon, R.E., and DiMichele, J.A. (1986) "Genetic variation in Fundulus heteroclitus: Geographic distribution" Amer. Zool. 26, 131-144.
• Ogo, S.H., Focesi, A., Cashon, R.E., Bonaventura, C., and Bonaventura, J. (1987) "Fluorescence studies of the binding of reduced NADPH to human hemoglobin A and its variant Hemoglobin Providence" Braz. J. Med. Biol. Res. 20(6), 755-758.
• Ogo, S., Focesi, A. Jr., Cashon, R.E., Bonaventura, J., and Bonaventura, C. (1989) "Interactions of nicotinamide adenine dinucleotides with varied states and forms of hemoglobin" J. Biol. Chem. 264(19), 11302-11306.
• Alayash, A.I., Cashon, R.E., and Bonaventura, J. (1989) "Modification of the intraerythrocytic hemoglobin S affinity for oxygen by a zinc chelator" Annals of N.Y. Acad. Sci. 565, 360-362.
• Alayash, A.I., Cashon, R.E., Bonaventura, J., Al-Quorain, A., and Omer, A.H.S. (1989) "Whole blood oxygen equilibrium curves in clinically mild sickle cell anemia patients" Med. Sci. Res. 17, 299.
• Brouwer, M., Cashon, R.E., and Bonaventura, J. (1990) "Functional properties of hemoglobin immobilized in coacervates prepared from gelatin A and polyanionic carbohydrates" Biotechnol. Bioeng. 35, 831-836.
• Boffi, A., Bonaventura, C., Bonaventura, J., Cashon, R.E., and Chiancone, E. (1991) "Oxidized dimeric Scapharca inaequivalvis: CO-driven perturbation of the redox equilibrium" J. Biol. Chem. 266(27), 17898-17903.
• Bonaventura, C, Cashon, R.E., Bonaventura, J., Perutz, M., Fermi, G., and Shih, D. (1991) "Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys ß66 --> Thr) and its isolated ß chains" J. Biol. Chem. 266(34), 23033-
• Bonaventura, C., Cashon, R.E., Colacino, J., and Hilderman, R. (1992) "Alteration of hemoglobin function by diadenosine 5',5'''-P1,P4-tetraphosphate and other alarmones" J. Biol. Chem. 267(7), 4652-4657.
• Brouwer, M., Cashon, R.E., and Bonaventura, J. (1992) "Carbodiimide-mediated coupling of benzenepentacarboxylate to human hemoglobin: structural and functional consequences" Biomat., Art. Cells and Immob. Biotech. 20(2-4), 323-326.
• Brouwer, M., Brouwer-Hoexum, T., and Cashon, R. (1993) "Crustaceans as models for metal metabolism: III. Interaction of lobster and mammalian metallothionein with glutathione" Marine Environmental Research 35, 13-17.
• Alayash, A.I., Fratantoni, J.C., Bonaventura, C., Bonaventura, J., and Cashon, R.E. (1993) "Nitric oxide binding to human ferrihemoglobins cross-linked between either alpha or beta subunits" Arch. Biochem. Biophys. 303(2), 332-338.
• Brouwer, M., Brouwer-Hoexum, T., and Cashon, R.E. (1993) "A putative glutathione-binding site in CdZn-metallothionein identified by equilibrium binding and molecular modeling studies" Biochemical Journal 294, 219-225.
• Kilbourn, R.G., Joly, G., Cashon, B., DeAngelo, J., and Bonaventura, J. (1994) "Cell- free hemoglobin reverses the endotoxin-mediated hyporesponsivity of rat aortic rings to *-adenergic agents" Biochem. Biophys. Research Comm. 199, 155-162.
• Alayash, A.I., Brockner Ryan, B.A., Fratantoni, J.C. and Cashon, R.E. (1994) "Redox reactivity of modified hemoglobins with hydrogen peroxide and nitric oxide: Toxicological implications" Art. Cells, Blood Subs. and Immob. Biotech. 22, 373-86.
• Alayash, A.I. and Cashon, R.E. (1994) "Reactions of nitric oxide and hydrogen peroxide with hemoglobin based blood substitutes" Ann. N.Y. Acad. Sci. 738, 378-381.
• Bonaventura, C., Arumugam, M., Cashon, R.E., Bonaventura, J., and Moo-Penn, W. (1994) "Chloride masks effects of opposing positive charges in HbA and Hb Hinsdale (ß139 Asn*Lys) that can modulate cooperativity as well as oxygen affinity" J. Mol. Biol. 239, 561-568.
• Bonilla, G.O., A. Focesi, Jr., C. Bonaventura, J. Bonaventura, and R. Cashon (1994) "Functional properties of the hemoglobin from the South American snake Mastigodryas bifossatus" Comp. Biochem. Physiol. 109A, 1085-1095.
• Cashon, R.E. and Alayash, A.I. (1995) "Reaction of crosslinked hemoglobins with hydrogen peroxide: Differential behavior of the ferryl intermediate" Arch. Biochem. Biophys. 316, 461-469.
• Rogers, M.S., Brockner Ryan, B., Cashon, R.E., and Alayash, A.I. (1995) "Effects of polymerization on the oxygen carrying and redox properties of diaspirin cross-linked hemoglobin Biochim. Biophys. Acta 1248, 135-142.
• Alayash, A.I. and Cashon, R.E. (1995) "Haemoglobin and free radicals: Implications for the development of a safe blood substitute" Molecular Medicine Today 1(3), 122-127.
• Cashon, R.E., Vayda, M. and Sidell, B. (1997) "Kinetic characterization of myoglobins from vertebrates with vastly different body temperatures" Comp. Biochem. Physiol. 117B (4), 613-620.
• Alayash, A.I., Brockner-Ryan, B.A., McLeod, L.L., Goldman, D.W., and Cashon, R.E., (1998) "Cell-free hemoglobin and tissue oxidants: Probing the mechanisms of hemoglobin cytotoxicity" in Blood Substitutes: Principles, Methods, Products, and Clinical Trials. Edited by T.M.S. Chang, Karger Landes Systems.
• Vayda, M.E., Londraville, R.L., Cashon, R.E., Costello, L. and Sidell, B.D. (1998) "Two distinct isoforms of fatty acid binding protein are expressed in heart ventricle of Antarctic fishes" Biochemical Journal 330(1), 375-382.
• Alayash, A. I., Brockner-Ryan, B.A., and Cashon, R.E. (1998) "Peroxynitrite-mediated heme oxidation and protein modification of native and chemically modified hemoglobins" Arch. Biochem. Biophys. 349(1), 65-73.
• Alayash, A.I., Brockner-Ryan, B.A., Eich, R.F., Olson, J.F., and Cashon, R.E. (1999) "Reactions of sperm whale myoglobin with hydrogen peroxide: effects of distal pocket mutations on the formation and stability of the ferryl intermediate" Journal of Biological Chemistry 274(4), 2029-2037.
• Hrinczenko, B.W., Schechter, A.N., Wojtkowski, T.L., Pannell, L.K., Cashon, R.E. and Alayash, A.I. (2000) "Nitric oxide-mediated heme oxidation and selective b-globin nitrosation of hemoglobin from normal and sickle erythrocytes" Biochemical and Biophysical Research Communications 275, 962-967.
• Alayash, A.I., Patel, R.P., and Cashon, R.E. (2001) "Redox reactions of hemoglobin and myoglobin: Biological and toxicological implications" Antioxidant and Redox Signalling 3(2), 313-327.

[Edit my profile]