07/21/04 (Forbes Lecture)

Wiring the Brain: The Logic and Molecular Mechanisms of Axon Guidance and Regeneration
Marc Tessier-Lavigne, Genentech

Introduction by Louis Ptácek, University of California, San Francisco

Lecture Abstract:
Neuronal growth cones navigate over long distances along specific pathways to find their correct targets, guided by four different mechanisms: contact attraction, chemoattraction, contact repulsion, and chemorepulsion.  These mechanisms act simultaneously and in coordinate fashion to direct pathfinding, and are mediated by mechanistically and evolutionarily conserved ligand-receptor systems.  This presentation will describe some of our recent advances in elucidating axon growth and guidance mechanisms, including the identification of novel axonal attractants, and the elucidation of mechanisms through which growth cones switch their responsiveness to guidance cues at intermediate targets from attraction to repulsion.  I will conclude by discussing the prospects for manipulating growth cone signal transduction pathways and the growth state of neurons to stimulate the regeneration of connections in the adult nervous system following injury, including paralyzing injuries to the spinal cord.


07/22/04 (Forbes Lecture)

Brain development and brain repair: Molecules and mechanisms that control nerve growth
Marc Tessier-Lavigne, Genentech

Introduction by Donald Price, The Johns Hopkins University School of Medicine

Lecture Abstract:
The brain is the most complex organ in our bodies.  It is made up of close to a trillion nerve cells (or neurons), each of which makes connections with, on average, hundreds of other nerve cells, to form the complex neuronal circuits that control all brain activities, including perception, emotion, the control of movement, and consciousness.  Remarkably, this pattern of connections among nerve cells is highly precise, and arises during embryonic and fetal development through the actions of specific molecules that control the formation of these connections.  Defects in this process can lead to brain miswiring, which may result in neurological or psychiatric disorders.  In this talk I will describe recent advances in identifying the molecules that direct the formation of neuronal circuits, and how this knowledge is providing tools to help regenerate neuronal connections following trauma or injury to the nervous system, including paralyzing injuries to the spinal cord.

References:
Long H, Sabatier C, Ma L, Plump A, Yuan W, Ornitz DM, Tamada A, Murakami F, Goodman CS, Tessier-Lavigne M. Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron. 2004 Apr 22;42(2):213-23.

Sabatier C, Plump AS, Le Ma, Brose K, Tamada A, Murakami F, Lee EY, Tessier-Lavigne M. The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons. Cell. 2004 Apr 16;117(2):157-69.

Steward O, Zheng B, Ho C, Anderson K, Tessier-Lavigne M. The dorsolateral corticospinal tract in mice: an alternative route for corticospinal input to caudal segments following dorsal column lesions. J Comp Neurol. 2004 May 10;472(4):463-77.

Dr. Marc Tessier-Lavigne is a world leader in the study of brain development and regeneration.  He has pioneered the identification of the molecules that direct the formation of connections among nerve cells to establish neuronal circuits in the mammalian brain and spinal cord.  He and his colleagues identified some of the first known chemoattractants and branching factors for developing nerve cells in vertebrates, the Netrin and Slit proteins.  They have also been at the forefront of discoveries on many other brain wiring proteins and receptor mechanisms.  The mechanisms he has identified are important for understanding how the human brain forms during normal development, and provide essential tools to assist regeneration of nerve connections following trauma or injury, such as paralyzing injuries to the spinal cord. Dr. Tessier-Lavigne was born in Trenton, Canada, and received a B.Sc. in Physics from McGill University, and a B.A. in Philosophy and Physiology from Oxford University, where he was a Rhodes Scholar.  He obtained his Ph.D. in Physiology in from University College London, and performed postdoctoral work at the MRC Developmental Neurobiology Unit in London and at Columbia University, where he was a Markey Scholar.  From 1991 to 2001 he was on the faculty at the University of California, San Francisco, and from 2001 to 2003 he served as the Susan B. Ford Professor in the School of Humanities and Sciences and Professor of Biological Sciences at Stanford University.  He was also an investigator with the Howard Hughes Medical Institute from 1994 to 2003.  In 2003, he joined Genentech, Inc. as Senior Vice President, Research Drug Discovery. Dr. Tessier-Lavigne serves on the editorial boards of several scientific journals, including the Board of Reviewing Editors of Science magazine, and he is co-editor in chief of Current Opinion in Neurobiology.  He also serves on the scientific advisory boards of a number of foundations and research organizations.  In 2000, he co-founded a biotechnology company, Renovis, Inc., which focuses on developing therapies for neurological and psychiatric disorders.  He is currently Chair of the Renovis Scientific Advisory Board.  Previously, he was a scientific advisor to Exelixis, Inc. Dr. Tessier-Lavigne is the recipient or co-recipient of a number of awards, including the Young Investigator Award of the Society for Neuroscience (USA), the Charles Judson Herrick Award of the American Association of Anatomists, the Ameritec Prize for contributions towards a cure for paralysis, the Fondation Ibsen Prize in Neuronal Plasticity, the Viktor Hamburger Award of the International Society for Developmental Neuroscience, and the Wakeman Award for regeneration research.   In recognition of his scientific contributions, Dr. Tessier-Lavigne has been elected a Fellow of the Royal Society (London), a Fellow of the Royal Society of Canada, and a Fellow of the American Association for the Advancement of Science.  In 1999, he was named a Canadian “Leader for the 21st Century” by Time magazine Canada.

Louis Ptácek, M.D. is a Professor in the Department of Neurology at the University of California at San Francisco and an Investigator at the Howard Hughes Medical Institute. He received his B.S. in Mathematics and his M.D. from Madison's University of Wisconsin in 1982 and 1986 respectively. After completing his internship at the University of Washington in 1987, Dr. Ptácek was a Resident and Chief Resident in Neurology at the University of Utah until 1990. He completed his post doctorate in Human Genetics there in 1993 and progressed through the ranks to become the Director of the university's Neurogenetics Program, a post he held from 1999 to 2003. Dr. Ptácek's work set the stage for a group of episodic disorders (including epilepsy, migraine, and cardiac arrhythmias) that he called 'Channelopathies' since they frequently result from ion channel gene mutations. He has also characterized the only Mendelian human circadian behavioral variant at both clinical and molecular levels with his collaborators Chris Jones and Ying-Hui Fu. Dr. Ptácek has served as an Ad Hoc member of NIH and National Institute of Neurological Disorders and Stroke (NINDS) and a standing member of the NCRR study sections. He has received several awards from the American Neurological Association, including its Presidents Award, its Travel Award, and its Derek Denny-Brown Neurological Scholar Award. He was also awarded the University of Utah School of Medicine's Golden Anniversary Prize for Distinguished Clinical Investigation.

Donald Price, M.D., Professor in the Departments of Pathology, Neurology, and Neuroscience, is the Director of the Alzheimer's Disease Research Center at The Johns Hopkins University School of Medicine. He graduated from Wesleyan University, received his M.D. from Albany Medical School, trained in Internal Medicine, Neurology, and Neuropathology (Massachusetts General Hospital), and completed a postdoctoral fellowship with Dr. Keith Porter at the Biology Laboratories at Harvard University. Dr. Price was appointed Assistant Professor at Harvard Medical School in 1970, and later, accepted a position at Johns Hopkins as Associate Professor and Director of the Division of Neuropathology. Dr. Price has made contributions to the understanding of several neurodegenerative diseases, [Alzheimer's Disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis (ALS)] by investigating the biology of these human illnesses; by creating and analyzing disease mechanisms in transgenic models with disease phenotypes of AD, PD, and ALS; and by using knockout strategies to identify and test new therapeutic targets in models of these illnesses.  His group generated one of the first transgenic models of Ab amyloidosis of AD and have targeted all of the genes encoding enzymes critical for generating Ab amyloid.  The demonstration that deletion of BACE1 completely prevents memory impairments and amyloid deposits in mutant APP/PS1 mice provides compelling evidence that this aspartyl protease is an extraordinarily attractive therapeutic target for AD. Price and colleagues have used similar approaches for PD and ALS.  Dr. Price has received a variety honors and awards, including the MetLife Award for Research, the Potamkin Prize, and two Javits Neuroscience Investigator Award (NINDS), among others. He is a Member of the Institute of Medicine of the National Academy of Science and a Trustee of the Grass Foundation. Dr. Price was the President of The Society for Neuroscience in 2000-2001 and was ranked by Science Watch in the top ten authors of high impact publications in neuroscience during the "Decade of the Brain".  Dr Price is a long term resident of Woods Hole.



About the Forbes Lecture
Since 1959, the special two-part Forbes Lecture has been supported by The Grass Foundation, a private foundation which supports research and education in neuroscience. The lectures are given in honor of pioneering neurobiologist Alexander Forbes. Traditionally, the Forbes lecturer also spends several weeks at the MBL, working alongside the Grass Fellowship Program.