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Nicolas Bazan

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Name  Nicolas Bazan

Nicolas Bazan httpswwwmedschoollsuhscedufacultyimagesnb
Books  Una Vida: A Fable of Music and the Mind

The dark madonna by nicolas bazan m d book trailer


Nicolas G. Bazan, MD, PhD is a neuroscientist and eye researcher, author, educator, mentor, developer, music enthusiast, and art lover. His research focuses on neurodegenerative diseases, aiming to understand endogenous modulation of neuroinflammatory signaling and of cell survival using cellular, molecular, and disease models including lipidomics. His lifelong quest has been to pin down events amenable to translation to help people affected by stroke, Alzheimer's disease, pain, blindness, and other diseases.

Contents

WEB EXCLUSIVE: Dr. Nicolas Bazan (Bioactive Lipids)


Current Appointments

  • The Ernest C. and Yvette C. Villere Chair for Research in Retinal Degeneration - Louisiana State University Health Sciences Center (LSUHSC), New Orleans, LA, 1984-
  • Professor of Ophthalmology, Biochemistry and Molecular Biology and Neurology, Louisiana State University Health Sciences Center (LSUHSC), School of Medicine, New Orleans, LA, 1981-
  • Director (Founder), Neuroscience Center of Excellence, LSUHSC, School of Medicine, New Orleans, LA, 1988-
  • Boyd Professor, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, LA, 1994-
  • Editor-in-Chief, Molecular Neurobiology (Springer), 1986-
  • Senate Member, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) in der Helmholtz-Gemeinschaft, nationwide research program (Germany), 2009-
  • Editorial Board, Cell Death and Disease, Nature Publishing Group, 2010-
  • Editorial Board, Cell Death and Differentiation, Nature Publishing Group, 2011-
  • Member, Biology of the Visual System Study Section, NIH, 2012-
  • Chair of the Louisiana State University Health Sciences Center (LSUHSC) Research Council/Translational Research Initiative, New Orleans
  • Biography

    Nicolas G. Bazan was born in Los Sarmientos, Tucuman, Argentina on May 22, 1942. He received his MD from the University of Tucuman School of Medicine, Argentina (1965) and was a postdoctoral fellow at Columbia University's College of Physicians and Surgeons and Harvard Medical School (1965–1968). The research that he performed at Harvard was the basis for his Doctor in Medical Sciences thesis (University of Tucuman, 1971). He became the founding director of the LSUHSC Neuroscience Center of Excellence in 1989.

    Scientific Contributions

    Bazan demonstrated that brain ischemia triggers the release of free essential fatty acids (arachidonic and docosahexaenoic acid) from membranes during seizures and ischemia through phospholipase A2. This finding has been referred to as the "Bazan Effect".

    In the early 70's his laboratory isolated a diacylglycerol containing docosahexaenoyl chains in C1 and C2 from the retina, demonstrated that this lipid is present in this tissue in relatively large proportions, and uncovered novel molecular species of phospholipids (containing two docosahexaenoyl chains; coined the term "supraenoic" molecular species) displaying very rapid turnover.

    In 1975, he and his colleagues showed that the brains of newborn mammals and adult poikilotherms accumulate free arachidonic acid sluggishly, correlating with the known resistance of these animals to anoxia. In contrast, mature homeothermic animals, vulnerable to relatively short periods of anoxia, rapidly accumulate arachidonic and docosahexaenoic acid as a result of phospholipase A2 activation. Also, his laboratory found that the diacylglycerol accumulated in the brain during ischemia is derived from inositol lipids and postulated that selective vulnerability at synapses engages degradation of inositol lipids. In 1980, he and his colleagues described those molecular species of phospholipids in photoreceptors contain two docosahexaenoyl chains per molecule, rather than a saturated chain at C1 and an unsaturated chain at C2, confirming their initial observation of the 70s. Also, he and his colleagues identified inositol lipid degradation and phospholipase A2 activation in neural cell damage in experimental epilepsy and stroke.

    He and his colleagues showed in 1979 that phospholipase A2 activation, which gives rise to brain free arachidonic and docosahexaenoic acid upon stimulation, is related to neurotransmission. In addition, he showed that the concept commonly described in textbooks, that the essential fatty acid docosahexaenoic acid is introduced through the acylation-deacylation cycle in retina membranes (and in other excitable membranes), is incorrect. Rather, they demonstrated that this fatty acid is introduced to a large extent through the de novo synthesis of phosphatidic acid.

    Then his laboratory identified an activating enzyme for docosahexaenoic acid with very low Km, which allows photoreceptors and other excitable membranes to retain this fatty acid. Also in a series of studies, they found that leukotrienes, HETEs (hydroxyeicosatetraenoic acids), inositol lipids and prostaglandins are key molecules in the communication between retinal pigment epithelial cells and photoreceptors.

    In 1985, Bazan and his colleagues provided evidence that retinal pigment epithelial cells retain docosahexaenoic acid within photoreceptors by a "short loop" between both cells, and a "long loop" between the liver and the retina. His laboratory further supported these concepts by demonstrating a deficit of docosahexaenoic and arachidonic acid in Usher’s syndrome. Then they demonstrated that phagocytosis by retinal pigment epithelial cells induces gene expression. During that time, Bazan and his colleagues found prostaglandin D synthetase in the interphotoreceptor matrix and cloned its receptor. They demonstrated that docosahexaenoic acid is transported from the post-Golgi network to the photoreceptor disk membranes with rhodopsin.

    Bazan and colleagues also showed that platelet-activating factor (PAF) is an endogenous neurotoxin and demonstrated neuroprotection by PAF antagonists. This included the finding that seizure-induced platelet-activating factor production activates gene expression, as well as a new neuroprotection site, the PAF receptor. Moreover, his laboratory found that PAF modulates glutamate release and is a retrograde messenger of long-term potentiation and that this "physiological PAF" enhances memory formation. Moreover, they found that PAF activates transcription of the inducible prostaglandin synthase, cyclooxygenase-2 (COX-2).

    Subsequently the Bazan laboratory demonstrated that the secretory phospholipase A2 modulates neuronal survival and glutamate transmission. Then, Bazan's laboratory in collaboration with the Stephen Prescott lab showed that neuronal diacylglycerol kinase epsilon is necessary in seizures and neuroprotection. In 2002 they showed that photoreceptors have a DNA repair mechanism that is induced by light damage and identified that genes are upregulated in models of retinal pathoangiogenesis.

    In 2003, Bazan and his colleagues coined the term “docosanoids,” which are enzyme-derived oxygenated messengers of docosahexaenoic acid, and in 2004 participated in the discovery of the synthesis and bioactivity of the first docosanoid, neuroprotectin D1 (NPD1). This paper relates how he and his colleagues discovered that NPD1 arrests apoptosis in retinal pigment epithelial cells at the pre-mitochondrial level.

    In 2011 Bazan and his colleagues found that DHA is neuroprotective in experimental stroke and that NPD1 is neuroprotective in experimental epilepsy.

    Research led by Bazan in 2015 also discovered a protein in the retina that is crucial for vision. Bazan and his colleagues reported on the key molecular mechanisms leading to visual degeneration and blindness. They discovered that adiponectin receptor 1 (AdipoR1) is a regulator of these RPE cell functions and demonstrated that AdipoR1 ablation results in DHA reduction. These results established AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoreceptors and RPE cells, thus preserving photoreceptor cell integrity.

    In 2015 Bazan and his colleagues also discovered gene interactions that determine whether cells live or die in such conditions as age-related macular degeneration and ischemic stroke. They worked with human RPE cells and an experimental model of ischemic stroke and discovered novel mechanisms in cells with the ability to activate pathways that crosstalk one to another and then assemble consolidated responses that decide cell fate. The study reported that, in retinal pigment epithelial cells, NPD1 induces nuclear translocation and cREL synthesis that, in turn, mediates BIRC3 transcription; thus BIRC3 silencing prevents NPD1 induction of survival against oxidative stress.

    In 2016 Bazan and his colleagues showed in "in vivo" rodent models of limbic epileptogenesis (LE) that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression, suggesting that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy.

    Recognitions

  • Javits Neuroscience Investigator Award: National Institute for Neurological Disorders and Stroke - National Institutes of Health, 1989
  • Citation Classic, "Neural Stimulation or Onset of Cerebral Ischemia Activates Phospholipase A2": Current Contents, Life Sciences, 1991
  • Elected Member, Royal Academy of Sciences, Spain, 1993
  • Boyd Professor, Louisiana State University, 1994
  • Elected Member, Dana Alliance for Brain Initiative, 1995
  • Elected Member, Royal Academy of Medicine, Spain, 1996
  • Guest of Honor, Inaugural Symposium, Frontiers in Neuroscience, Wallenberg Neuroscience Center, Lund University, Sweden, 1996
  • Fellow, Royal College of Physicians of Ireland, Dublin, 1999
  • Endre A. Balazs Prize, International Society of Eye Research, 2000
  • President, American Society for Neurochemistry, 1991-2001
  • 1st Leon Wolfe Lecturer, Montreal Neurology Institute, Canada, 2004
  • Proctor Medal, Association for Research in Vision and Ophthalmology, Florida, 2007
  • Association for Research in Vision and Ophthalmology Silver Fellow, 2009
  • Association for Research in Vision and Ophthalmology Gold Fellow, 2011
  • Chevreul Medal, Paris, France, 2011
  • Alkmeon International Prize, 2011
  • Keynote Speaker and Excellence Award, European Association for Vision and Eye Research, 2013
  • Medal, Miroslaw M. Mossakowski, Polish Academy of Sciences, 2013
  • The Pan-American Association for Biochemistry and Molecular Biology Plenary Lecturer, 56th Int. Conf. Bioscience of Lipids, Iguazu, Argentina, 2015
  • Gradle Medal and Lecture. The Pan-American Association of Ophthalmology/World Ophthalmology Congress, Guadalajara, Mexico, 2016
  • Community Leadership Awards

  • Role Model Awardee, Young Leadership Council of New Orleans, 1994
  • CityBusiness 2002 Innovator of the Year Award, New Orleans, LA, 2002
  • The Alzheimer’s’ Association Greater New Orleans Chapter Award, New Orleans, LA, 2002
  • Career Service Award, 20 years, LSU Health Sciences Center, New Orleans, LA, 2003
  • Family Services of Greater New Orleans (Ten Outstanding Persons) Award, New Orleans, LA, 2003
  • New Orleans CityBusiness Health Care Heroes Award, 2008
  • Junior Achievement Business Hall of Fame, New Orleans, LA, 2010
  • Excelencia Award for Medical Research and Business, Hispanic Chamber of Commerce of Louisiana, New Orleans, LA, 2011
  • Translational Medicine and Industry

    Start-Up Companies

  • InSite Vision (Alameda, California): Scientific Co-Founder, 1987
  • St. Charles Pharmaceuticals (New Orleans, Louisiana): Scientific Founder, 1997
  • Patents

  • United States Patent No. P9501549; Inventors: Nicolas G. Bazan and Julio Alvarez-Builla Gomez and Assignee: Spain, “Nuevos derivados de N-acil-4-hidroxifenilamina con propiedades analgésicas y formulaciones farmaceuticas que los contienen.” 1995
  • United States Patent No. 5,554,636; Inventors: Nicolas G. Bazan and Julio Alvarez-Builla Gomez and Assignee: LSUMC, “N-acylated 4-hydroxyphenylamine derivatives with analgesic properties and pharmaceutical compositions containing them” and corresponding International Application No. PCT/US96/05456, published as International Publication No.WO 96/32940; Canadian application no. 2,218664, European application no.96915332.9, and Japanese application no. B-531944. 1996
  • United States Patent No. 5,621,110; Inventors: Nicolas G. Bazan and Julio Alvarez-Builla Gomez and Assignee: LSUMC, “Process for preparing N-acylated 4-hydroxyphenylamine derivatives with analgesic properties.” 1997
  • United States Patent Filed “02/25/2002: Inventors: Jay Hunt, Haydee Bazan, Victor Marcheselli, Julio Alvarez-Builla Gomez, Nicolas G. Bazan and Assignee: LSUHSC, "Platelet-activating factor antagonist inhibition of angiogenesis and tumor growth induced by basic fibroblast growth factor.” 2002
  • United States Patent No. 6,653.311; Inventors: Nicolas G. Bazan, Carlos Sunkel, Julio Alvarez-Builla Gomez and Assignee: LSUHSC, “5-Lipoxygenase inhibitors: (2-azinylamino) quinone Derivatives.” 2003
  • United States Patent No. 6,566,359; Inventors: Nicolas G. Bazan, Carlos Sunkel, Victor Marcheselli and Julio Alvarez-Builla Gomez and Assignee: LSUHSC, “2,4,6-Trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid esters as neuroprotective drugs.” LAU-0901. 2003
  • United States Patent Application Serial No. 10/459,911: Inventors: Nicolas G. Bazan, Carlos Sunkel, Dennis Paul, Julio Alvarez-Builla and Assignee: LSUHSC, “Synergistic combinations including N-acylated 4-hydroxyphenylamine derivatives with caffeine.” 2003
  • United States Patent Application Serial No. 60/589,445: Inventors: Nicolas G. Bazan, Walter J. Lukiw, Charles N. Serhan*, and Assignee: LSUHSC, “Neuroprotective and anti-inflammatory bioactive docosaehexanoic acid mediators in Alzheimer’ disease.” 2004
  • United States Patent Application Serial No. 10/911,835: Inventors: Nicolas G. Bazan, Charles N. Serhan, Victor L. Marcheselli, Pranab K. Mukherjee, Sebastian G. Barreiro, Walter J. Lukiw, Song Hong, Karsten Gronert, and Albert E. Musto and Assignee: LSUHSC, “Neuroprotectin D1 protects against cellular apoptosis, stroke damage, Alzheimer’s disease and retinal diseases.” 2004
  • United States Patent Filed pending: Inventors: Salomon Esquenazi, Haydee E.P. Bazan, Nicolas G. Bazan and Assignee: LSUHSC, “Topical treatment with nerve growth factor and docosahexaenoic acid in corneal refractive surgery.” 2004
  • United States Patent No. 6,806,291; Inventors: Nicolas G. Bazan, Carlos Sunkel, Anthony Vaccarino, Julio Alvarez-Builla, and Assignee: LSUHSC, “Analgesic compounds, their synthesis and pharmaceutical compositions containing them”; and corresponding U.S. Patent Application Serial No. 10/682,744, filed October 9, 2003; and corresponding International Application No. PCT/US2004/033609, filed October 12, 2004.
  • United States Patent Application Serial No. 10/292,105; Inventors: Nicolas G. Bazan, Carlos Sunkel, Dennis Paul, Julio Alvarez-Builla Gomez and Assignee: LSUHSC, “Synergistic combinations including N-acylated 4-hydroxyphenylamine derivates with caffeine”; published as U.S. Patent Application Publication No. 2004/0092541; and corresponding, International Application No. PCT/US2003/036039, filed November 12, 2003, and published as International Publication No. WO 20004/043460. 2004
  • Teaching and Educational Programs

  • Department of Biology, University of the South, Bahía Blanca, Argentina - Founder of this department in 1970 and served as its director until 1973
  • Institute of Biochemical Investigations, Universidad Nacional del Sur Consejo Nacional de Investigaciones Cientificas y Técnicas, Bahía Blanca, Argentina - Bazan founded this institute in 1970 and served as its director until 1981
  • Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans - Founder of this Center in 1988 and continues to serve as its director. The Neuroscience Center pursues a multidisciplinary approach to neuroscience education and research. The primary mission of the Center is to foster and conduct science of the highest caliber that advances the understanding of brain function and diseases that affect the nervous system. A major role of the Center is to mentor the development of neuroscientists and clinician-neuroscientists through fundamental and translational research.
  • Interdisciplinary Neuroscience Graduate Program - Bazan currently heads this program at the LSUHSC Neuroscience Center of Excellence; it offers pre-doctoral research training in fundamental neurosciences and PhD and MD/PhD degrees
  • Summer Undergraduate Neuroscience (SUN) Program - Bazan organized this program at the LSUHSC Neuroscience Center of Excellence to offer Louisiana's undergraduate students hands-on experiences in laboratory research and education in the neurosciences, with the goal of stimulating an interest in medicine, neuroscience and research as a career.
  • Wine

    In 2005, Bazan launched his family wine label, "Nicolas Bazan Wines." The Bazan Wine project is a collaborative effort between Dr. Bazan and Dr. Mark Wahle. Dr. Wahle is a medical doctor with a degree in enology from University of California at Davis. Dr. Wahle established the Wahle Family vineyards in Yamhill, Oregon. The Bazan Block comprises 20 acres of the Holmes Hill vineyard site. Grapes for the Nicolas Bazan Wines are derived mainly from this Block.

    Faith

    Bazan has a strong faith. He actively participates in Roman Catholic Church activities, and when asked he states that his dedication is personal and not to be displayed in the press. He believes that the scientific exploration for new knowledge and uncovering fundamentals of brain function comprise a different, non-competing sphere as compared with faith.

    Novels

    In 2009, Bazan published the fictional novel "Una Vida: A Fable of Music and the Mind", a tale of a neuroscientist's personal quest to uncover the history of a New Orleans street performer stricken with Alzheimer's disease. In the book, neuroscientist Alvaro Cruz finds himself haunted by a recurring dream of a banjo player in an elusive cornfield, leading him on a personal quest to uncover the mysterious past of a New Orleans street singer known as Una Vida. Stricken with Alzheimer's, she can only offer tantalizing clues about her past through her mesmerizing vocals, incredible recollection of jazz lyrics and the occasional verbal revisiting of a fascinating life that's fading quickly into the recess of her mind. As Cruz searches for Una Vida's true identity, he learns profound lessons about the human psyche, the nature of memory - and himself. This book was adapted into the motion picture "Of Mind and Music".

    References

    Nicolas Bazan Wikipedia


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