JOSEPH BONAVENTURA
Professor, Cell Biology, Duke University
Professor at Large, University of Puerto Rico
Director, NIH Centers of Biomedical Research Excellence (COBRE II & III): Protein Structure, Function and Dynamics, Center for Computational Molecular and Systems Biology, University of Puerto Rico

Contact Information
University of Puerto Rico at Mayaguez
Department of Chemistry
(PH) 787-832-4040 x3294
(FX) 787-833-0565
University of Puerto System-Wide Research Resource Center Rio Piedras
(PH) 787-764-8369
(FX) 787-756-7717
joeb@duke.edu

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Education

	PhD	Biochemistry, University of Texas, Austin, 1968
	BA	Zoology/Chemistry, San Diego State College, California, 1964

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Experience

	2003-present	Professor at Large, University of Puerto Rico
	2003-present	Director, NIH COBRE II, Center for Research in Protein Structure, Function, and Dynamics
	2004-present	Director, NIH COBRE III, Center for Computational Molecular and Systems Biology
	1990-present	Professor, Duke University and Duke University Medical Center (Cell Biology) and Nicholas School of the Environment Marine Laboratory
	1978-1994	Founding Director, Duke University Marine Biomedical Center
	1988-1990	Associate Professor, Duke University Medical Center (Physiology) and Duke University and Duke University Marine Laboratory
	1984-1988	Associate Professor, Duke University Medical Center (Biochemistry) and Duke University Marine Laboratory
	1975-1984	Assistant Medical Research Professor of Biochemistry, Duke University Medical Center (Biochemistry) and Duke University Marine Laboratory
	1975-1980	American Heart Association Established Investigator
	1972-1975	Associate Professor, Duke University Medical Center (Biochemistry) and Duke University Marine Laboratory
	1972	Postdoctoral Fellow, European Molecular Biology Organization(EMBO), Rome, Italy
	1971	Postdoctoral Fellow, American Cancer Society, Rome, Italy
	1969	NIH Postdoctoral Fellow, California Institute of Technology

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Selected Publications

1. Bonaventura, J. and Lance V.P. 2001. Nitric Oxide, Invertebrates and Hemoglobin, Amer. Zool. , 41, 346-359.
2. Marcinek, D. J., J. Bonaventura, J. B. Wittenberg and B. A. Block. 2001. Oxygen affinity and amino acid sequence of myoglobins from enothermic and ectothermic fish. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 280(4):R1123-1133.
3. McMahon, T. J., A. S. Stone, J. Bonaventura, D. J. Singel and J. S. Stamler. 2000. Functional coupling of oxygen binding and vasoactivity in S-nitrosohemoblobin. Journal of Biological Chemistry 275: 16738-16745.
4. Kuo, R. C., G. T. Baxter, S. H. Thompson, S. A. Stricker, J. Patton, J. Bonaventura and D. Epel. 2000. Nitric oxide is a necessary and sufficient requirement of egg activation at fertilization. Nature 406(6796): 633 - 636.
5. Minning, D. M., A. J. Gow, J. Bonaventura, R. Braun, M. Dewhirst, D. E. Goldberg and J. S. Stamler. 1999. Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase' [see comments]. Nature 401(6752):497-502.
6. McMahon, T. J., Stone A. E., Bonaventura, J. and Stamler, J. S. 1999b. S-nitrosylation of hemoglobin increases its oxygen affinity. American Journal Of Respiratory and Critical Care Medicine 159(3): A352.
7. McMahon, T. J., A.E. Stone, J. Bonaventura, D.J. Singel and J.S. Stamler. 1999a. Thermodynamic linkage relationships in S-nitrosohemoglobin: Oxygen binding and vasoactivity. Free Radical Biology and Medicine 27:240.
8. Stamler, J. S., L. Jia, J. P. Eu, T. J. McMahon, I. T. Demchenko, J. Bonaventura, K. Gernert and C. A. Piantadosi. 1997. Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276(5321):2034-2037.
9. Mylvaganam, S. E., C. Bonaventura, J. Bonaventura and E. D. Getzoff. 1996. Structural basis for the root effect in haemoglobin. Nature Structural Biology 3(3):275-283.
10. Jia, L., C. Bonaventura, J. Bonaventura and J. S. Stamler. 1996. S-nitrosohaemoglobin: A dynamic activity of blood involved in vascular control. Nature 380:221-226.

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Selected from 50 Patents

1. U.S . Patent No. 5,998,2000. (Issued 12/7/2000) Anti-fouling methods using enzyme coatings.
2. U.S. Patent No. 6,153,186 (Issued 11/28/2000) Red blood cells loaded with S-nitrosothiol and uses therefor.
3. U.S. Patent No. 6,103,690 (Issued 08/15/2000) Prevention or inhibition of pathogenic syndromes caused by nitric oxide overproduction using iron-containing hemoprotein.
4. U.S. Patent No. 6,020,308 (Issued 02/01/2000) Methods for Improving Therapeutic Effectiveness of Treatment of Vascularization Disorders.
5. U.S. Patent No. 5,998,200 (Issued 12/7/1999) Anti-fouling methods using enzyme coatings.
6. U.S. Patent No. 3,827,693 (Issued 10/22/1998) Expression of Recombinant Hemoglobin and Hemoglobin Variants to Yeast.
7. U.S. Patent No. 5,773,417 (Issued 6/30/1998) Human serum albumin-porphyrin complexes with the ability to bind oxygen and therapeutic uses thereof.
8. U.S. Patent No. 5,480,866 (Issued 02/02/96) Hemoproteins for Inhibition of Nitric Oxide-mediated Hypotension and Septic Shock.
   

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Research Interest

Duke University: Dr. Joseph Bonaventura's research involves marine organisms found in diverse environments. Since moving to Duke from Rome, Italy, he has focused on biochemical studies on the structural and functional diversity of marine. The organismal adaptations have been shown to be manifest by diversity at the molecular level. Red cells and respiratory proteins of marine organisms are being studied in order to increase the understanding of molecular adaptations and the mechanisms that give rise to functional flexibility. The kinetics and equilibria of ligand binding to hemoglobins, hemocyanins, and cytochrome c oxidase are studied with emphasis on the reactivity of these proteins as regulated by metabolic effectors. These studies are complemented by work in the Protein Engineering and Technology Laboratory where properties of chemically modified, crosslinked, and immobilized forms of biologically active molecules are characterized.

The basic studies have been frequently complimented by inventions and developments that allow as well as facilitate the transfer of fundamental biochemical mechanisms into ?products?. There has been a wide diversity of them and patents, trade secrets and novel systems approaches to energy production under water have protected their way to the market place. Some selected US Patents are listed below. Many people have helped in the discovery and inventions and they are listed in the issued Patents as co-inventors. The first US Patent, issued in 197X, stemmed from a research Grant from the US Office of naval Research. This basic Research Project had, as some of its goals, the study of human and marine organisms hemoglobins. However, as a potential product of the work Dr. Bonaventura proposed that by making use of the principles by which fish specialized hemoglobins ?pump? oxygen from its dissolved state in the seawater to the gaseous state in the swim bladder, he might be able to invent or construct a comparable system for underwater human life support. After all, he stated, ?fish having the same mass as human beings use about the same amount of hemoglobin for all of their metabolic oxygen needs.? ?This amount?, he added, ?is about 750 grams of hemoglobin and might even be reduced by more than an order of magnitude, i.e., a hemoglobin mimetic could be made which is 1/100 th the mass of the hemoglobin protein molecule, making the amount of carrier required to support one person under water in the range of 30 grams! Through hard work and serendipity, this ?pipe dream? came true and one of the largest patent sales in Duke history came about. During this time, Biosponge Incorporated was founded and it continues to function, serving as an entity that can facilitate the transfer of non-Duke, or University licensed technologies into salable products.

The worldwide publicity about the ?Artificial Gill? led to many offers for development grants and contracts, leading to, among other things a Fish Feeding Stimulant, Mann's Bait Company FS 454, which has been used in ?Jelly Worms? for Bass fishing. And the founding of a Business Venture, Biosponge Aquaculture Products, for making high quality fish feeds manufactured from high quality foods that would be otherwise unpalatable to growing fish. Biosponge Aquaculture Products had notable success in creating a fish food for aquaculture that produced more pounds of fish per pound of food than any other product ever developed.

Similarly, a consumer products company, Sunshine Makers (whose magnificent Motto is EGBAR , Everything's Gonna Be Allright! ), wanted to produce a Biosponge having many of the properties of their lead product, Simple Green. Dr. Bonaventura made such a product, the Simple Green Biosponge, which, among other things works via a rather non-intuitive discovery that ?Immobilized Detergents? functin in a detergent-like activity without having to leach out of the polymer to which they are immobilized.

Perhaps most notably in the ?Translational Research? of Dr. Bonaventura, a private family, owners of the Stroh Brewery Company, in 1987, began support of a Recombinant Human Hemoglobin project on the development of a synthetic blood substitute for humans. The project involved a detailed study of structure-function relationships in the human hemoglobin molecule and included site-directed mutagenesis of hemoglobin genes in order to create tailor-made molecules that target oxygen delivery to specific tissues and organs.

The Nobel Prize winning (1998 Physiology or Medicine Nobel to Lou Ignarro, Bob Furchgott and Ferid Murad, for NO identified as EDRF, Endothelium- Derived Relaxing Factor, and NO activation of Guanylate Cyclase) discoveries of Nitric Oxide's physiological and pharmacological wide-ranging effects led to a redirection of the Synthetic Blood Project. That new focus, led by private funding, led to a major effort of research and development on the biochemistry of Nitric Oxide in the human body and the development of a hypothesis of how this simple molecule might act as a regulator of the biosphere. These studies led to several patents concerning the therapeutic use of hemoglobin and red blood cells. In 2003, Phase III Clinical Trials ((Pivotal Trials) began on a hemoglobin-based product to treat Septic Shock/Systemic Inflammatory Response Syndrome (SIRS). While in North Carolina , he is mostly in residence at the Nicholas School of the Environment Marine Laboratory in Beaufort.

In October of 2003, Dr. Bonaventura added Puerto Rico as a place where he loves. In Puerto Rico, he became a System-wide Professor at Large and Director of a NIH Center for research in Protein, Structure, Function and Dynamics (see www.cobre2.uprm.edu). This is a Multi-Campus Center and involves the UPR Campuses in Mayaguez , Rio Piedras, Humacao and of Medical Sciences in San Juan . He has set up a protein research laboratory in the Chemistry Department in Mayaguez (see www.uprm.edu/~jbonaventura ). In 2004, he became the Principal Investigator and Director of a Nascent Center of Computational Molecular and Systems Biology. This Center is also Multi-Campus and adds faculty from another Campus, in Cayey, to the Center. This Center has at its Central Core, a group of World Class mathematicians, computer scientists and statisticians who are developing novel tools and methods that allow for new views on how ?biology works? and an approach to biological understanding that couples reductionistic and holistic investigation. The website is being created in October/November, 2004 and will be posted as soon as it is installed.

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