Nicolas Bazan

Current Appointments

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

Community Leadership Awards

Translational Medicine and Industry

Start-Up Companies

Patents

Teaching and Educational Programs

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".