Nanotechnology and Translational Research

We have developed a novel nanoparticle platform for topical and systemic drug delivery. The platform is capable of sustained delivery of therapeutic levels of nitric oxide. The high collaborative research program consists of nanoparticle platform development, platform characterization, preclinical applications including wound healing, antimicrobial therapies (MRSA, TB, Malaria), topical treatment of erectile dysfunction, hypertension and peripheral vascular disease, enhanced MRI imaging and targeted drug delivery. The goal is tissue specific drug delivery with imaging capability.

Protein Dynamics, Reactivity, Osmolytes and Solvent Slaving

We seek to understand how solvent motions modulate functionally important protein dynamics. Our approach focuses on the water surrounding the protein, the different categories of protein dynamics that contribute to functionality and how the interplay between water and protein dynamics is modulated by osmolytes.

Hemoglobin based blood substitutes and the role of NO/nitrite in the control of vasoactivity.

Dr. Friedman is the Director of the Einstein Blood Substitute Program Project which seeks through a multidisciplinary effort to create acellular hemoglobin based blood substitutes for clinical use. A major focus is on the biophysical mechanisms through which hemoglobin in the presence of nitrite can generate stable nitrosothiols that cause vasodilation.

Roche, C.J., Guo, F. and Friedman, J.M. (2006) Molecular level probing of preferential hydration and its modulation by osmolytes through the use of pyranine (HPT) complexed to hemoglobin. J Biol Chem 281 38757-68. Nacharaju, P., J. M. Friedman, et al. (2007).

"Combining the influence of two low O2 affinity-inducing chemical modifications of the central cavity of hemoglobin." Biochemistry46(15): 4554-64.Samuni, U., D. Dantsker, et al.(2007).

"Ligand recombination and a hierarchy of solvent slaved dynamics: The origin of kinetic phases in hemeproteins." Gene 398(1-2): 234-48. Samuni, U.; Roche, C. J.; Danstker, D.; Friedman, J. M., Conformational dependence of hemoglobin reactivity under high viscosity conditions: the role of solvent slaved dynamics 2007, JACS 129(42):12756-64. Cabrales, P.; Friedman, J. M., Mechanisms for Why PEGylated Hemoglobins Can Function as Perfusion Enhancing Blood Substitutes. Transfusion Alternatives in Tranfusion Medicine 2007, 9, 281-293. Samuni U, Roche CJ, Dantsker D, Friedman JM. 2008.

T and R State Tertiary Relaxations in Sol-Gel Encapsulated Hemoglobin In: M. Bolognesi G. di Prisco, C. Verde, editor. Dioxygen Binding and Sensing: Springer. p 134-150.D. Giordano, L. Boechi, A. Vergara, M.A. Marti, U. Samuni, D. Dantsker, L. Grassi, D.A. Estrin, J.M. Friedman, L. Mazzarella, G. di Prisco, and C. Verde, The hemoglobins of the sub-Antarctic fish Cottoperca gobio, a phyletically basal species--oxygen-binding equilibria, kinetics and molecular dynamics. Febs J 276 (2009) 2266-77. Friedman, A. J., G. Han, et al.(2008).

"Sustained release nitric oxide releasing nanoparticles: characterization of a novel delivery platform based on nitrite containing hydrogel/glass composites." Nitric Oxide 19(1): 12-20.Samuni U, Friedman JM. 2005.

Proteins in motion: resonance Raman spectroscopy as a probe of functional intermediates. Methods Mol Biol 305:287-300.Das, T.K., Dewilde, S., Friedman, J.M., Moens, L. and Rousseau, D.L. (2006) Multiple active site conformers in the carbon monoxide complexes of trematode hemoglobins.

J Biol Chem 281, 11471-9.Samuni U, Roche CJ, Dantsker D, Juszczak LJ, Friedman JM. (2006) Modulation of Reactivity and Conformation within the T-Quaternary State of Human Hemoglobin: The Combined Use of Mutagenesis and Sol-Gel Encapsulation. Biochemistry 45(9):2820-35. Navati, M. S. and Friedman, J. M., (2006).

Sugar-derived glasses support thermal and photo initiated long range electron transfer processes over macroscopic distances. J Biol Chem 281 36021-8.Roche, C.J., Dantsker, D., Samuni, U. and Friedman, J.M. (2006) Nitrite Reductase Activity of Sol-gel Encapsulated Deoxy Hemoglobin: Influence of Quaternary and Tertiary Structure. .J. Biol. Chem. 281 36874-82. Roche, C.J., Guo, F. and Friedman, J.M. (2006) Molecular level probing of preferential hydration and its modulation by osmolytes through the use of pyranine (HPT) complexed to hemoglobin. J Biol Chem 281 38757-68.Nacharaju, P., J. M. Friedman, et al. (2007).

"Combining the influence of two low O2 affinity-inducing chemical modifications of the central cavity of hemoglobin." Biochemistry46(15): 4554-64.Samuni, U., D. Dantsker, et al.(2007).

"Ligand recombination and a hierarchy of solvent slaved dynamics: The origin of kinetic phases in hemeproteins." Gene 398(1-2): 234-48. Samuni, U.; Roche, C. J.; Danstker, D.; Friedman, J. M., Conformational dependence of hemoglobin reactivity under high viscosity conditions: the role of solvent slaved dynamics 2007, JACS 129(42):12756-64.Ouellet, Y. H., R. Daigle, et al. (2008).

"Ligand binding to truncated hemoglobin N from mycobacterium tuberculosis is strongly modulated by the interplay between the distal heme pocket residues and internal water." J Biol Chem. 283(40): p. 27270-8. M.S. Navati, and J.M. Friedman, (2009)Reactivity of glass-embedded met hemoglobin derivatives towards external NO: implications for nitrite-mediated production of bioactive NO. JACS In press. Martinez, L. R., Han, G., Chacko, M., Mihu, M. R., Jacobson, M., Gialanella, P., Friedman, A. J., Nosanchuk, J. D. & Friedman, J. M. (2009) Antimicrobial and Healing Efficacy of Sustained Release Nitric Oxide Nanoparticles Against Staphylococcus Aureus Skin Infection.J Invest Dermatol.Han, G, Tar, M., Srini, D.K., Friedman, A, Melman, A., Friedman, J., and Davies, K.P. (2009) Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction J. Sexual Med. (In press).Friedman, A, and Friedman, J. (2009) New biomaterials for the sustained release of nitric oxide: past, present and future. Expert Opinion on Drug Delivery (In press). F. Guo, and J.M. Friedman, (2009)Charge Density-Dependent Modifications of Hydration Shell Waters by Hofmeister Ions. J Am Chem Soc.(In press)