GeneExpression Systems & Appasani Research Conferences (ARCEI.ORG)
Jointly Presents

Second International
Neuron to Synapse 2010 Meeting
On
‘Neurobiology to Neurodegenerative Diseases & Therapeutics’

June 7 – 8, 2010
Holiday Inn Midtown at 57th Street, New York City, NY, USA

“A Unique Theme to Combine Biology of Neurosynapses, Cognition, Memory & Diseases”

Topics or Highlights of the Meeting:

Neurodevelopment & Mechanisms
Sensory & Motor Systems
Cognition & Behavior
Disorders of Nervous System
Drug Development


Focus of the Theme Meeting:

Brain diseases, in particular neurodegenerative diseases, represent a growing public health concern. Understanding the biology of neuronal cells (neurons) and their communication with neighboring cells at synapses is crucial in order to know the defects and pathophysiology of brain disorders. To discover and develop innovative drug compounds for these central nervous system diseases it is essential to gather intellectual minds from academia, biotech and pharmaceutical industries to have a forum. Such forum will enhance knowledge and dissipate of data and ideas which will ultimately bring more scientific and business collaborations.

The conference will bring together experts and young researchers with diverse backgrounds in molecular and cellular neurobiology, biochemistry, electrophysiology, behavior, cognition, perception, and disease biology, and the first conference discussing new developments in this highly interdisciplinary area of brain research. The conference should be interesting for graduate students, postdoctoral fellows, professors from academia and scientists, directors and executives from industry, as well as for anyone interested in brain functions and their associated diseases. Authorities in the filed will be invited as key speakers. Few speakers will be also selected from the applicants, based on the submitted abstracts. Dedicated time will be allowed for presentation of posters and viewing the exhibits and to know the available cutting-edge reagents, services in the field.

AGENDA/SPEAKERS

Click Here For Agenda

Monday, June 7, 2010
8:00 A.M: Registration Open
9.00 AM – 5.30 PM Scientific Sessions

Tuesday, June 8, 2010
8:00 A.M: Registration Open
9.00 AM – 3.30 PM Scientific Sessions


Scientific Committee:

	Krishnarao Appasani, Ph.D., MBA Founder & CEO GeneExpression Systems, Inc, Waltham, MA, USA
	Eric J. Nestler, MD, PhD. Professor & Chair of Neuroscience Nash Family Professor of Neuroscience and Director of the Mount Sinai Brain Institute, New York, NY, USA Title:Epigenetic Mechanisms of Drug Addiction
	Paul Lombroso, MD Elizabeth Mear and House Jameson Professor of Neurobiology Associate Professor, Child Study Center Yale University, New Haven, CT, USA Title: Alzheimer’s disease: Taking STEPs to Improve Cognition

Keynote Speakers:

	Robert B. Darnell, M.D., Ph.D. Investigator, Howard Hughes Medical Institute Senior Attending Physician Robert and Harriet Heilbrunn Professor Laboratory of Molecular Neuro-oncology Rockefeller University, New York, NY USA Title: RNA regulation in human brain diseases
	Joseph E. LeDoux, PhD. Henry and Lucy Moses Professor of Science Professor of Neuroscience and Psychology New York University Director of the Center for the Neuroscience of Fear and Anxiety Title: Biological mechanisms of emotional memory
	Joan Fallon, Ph.D. CEO Curemark LLC Rye, NY USA Title: Autism: Biology and drugs

Other Speakers:

	Stewart A. Anderson, M.D. Associate Attending Psychiatrist (New York-Presbyterian Hospital) Associate Professor of Psychiatry in Neuroscience Weill Cornell Medical College, New York, NY USA Title: Cortical interneuron fate determination, and the generation of cortical interneurons from embryonic stem cells
	Ottavio Arancio, MD, Ph.D. Assistant Professor of Pathology Columbia Medical School, New York, NY USA Title: Amyloid-beta: From Physiology to Pathology
	Amy F.T. Arnsten, Ph.D. Professor of Neurobiology Director of Graduate Studies Yale University, New Haven, CT USA Title: Rescuing prefrontal cortical gray matter in neuropsychiatric illness
	Sanghamitra Bandyopadhyay, Ph. D.                     Scientist, Developmental Toxicology Indian Institute of toxicology Research (CSIR), Lucknow, UP, India Title: As, Cd and Pb synergistically promotes apoptosis in astrocytes and damages blood brain barrier in developing rat brain with altered neurobehavior
	David C. Bloom, Ph.D. Professor, Molecular Genetics and Microbiology University of Florida College of Medicine, Gainesville, FL USA Title: Use of Viral Vectors to Restore Hippocampal Synaptic Function in a Mouse Model of FRAGILE X SYNDROME
	Aiden Corvin, MB, MRCPsych, PhD. Senior Lecturer in Psychiatry & Director of Research at the School of Medicine St James's Hospital, Trinity College Dublin, Dublin Ireland Title: Emerging mechanisms for schizophrenia aetiology: lessons learned from genomics
	Lila Davachi, Ph.D. Assistant Professor Department of Psychology New York University, New York, NY USA
	Wenzhen Duan, M.D., Ph.D Assistant Professor Division of Neurobiology, Department of Psychiatry Director, Translational Neurobiology laboratory Faculty, Baltimore Huntington's Disease Center Johns Hopkins University School of Medicine, Baltimore, MD USA Title:Potential therapeutic targets for Huntington’s disease: lessons learned from calorie restriction
	Robert Hawkins, PhD Professor of Neuroscience, Psychiatry Columbia University, New York, NY USA Title: Role of spontaneous transmitter release in learning-related synaptic plasticity
	Shin-ya Kawaguchi, Ph.D. Assistant Professor, Dept. Biophysics Kyoto University, JAPAN Title: Systems Biology of Plasticity at Inhibitory Synapses
	David A. Lowe, PhD Chief Scientific Officer & Executive Vice President. Research & Development Psychogenics Inc., Tarrytown, NY USA
	Youming Lu, PhD, MD Professor of Neurology and Neuroscience Bollinger Professor of Alzheimer’s Diseases Department of Neurology and Neuroscience Center LSU School of Medicine, New Orleans, LA USA
	Patrick C May, PhD Research Fellow Lilly Neuroscience, Lilly Research Laboratories Lilly Corporate Center, Indianapolis, IN, USA Title: Status and Future of Secretase Inhibitors
	Kenneth J. Rhodes, PhD Vice President, Discovery Neurobiology Biogen Idec., Cambridge, MA, USA
	Ian L.Scott, PhD Senior Director of Chemistry and Biology Acucela, Inc., Bothell, WA USA Title:  Visual Cycle Modulation as an Approach to the Treatment of AMD
	Songhai Shi, Ph.D. Lab Head, Bristol Myers Squibb/James D. Robinson III Junior Faculty Chair Memorial Sloan-Kettering Cancer Center, New York, NY USA
	Alistair Stewart, PhD Director, Corporate Development Allon Therapeutics, Inc. Vancouver, BC, Canada Title: Phase 2 clinical trials of a novel neuroprotective drug, davunetide (AL-108) for the treatment of Alzheimer’s disease and frontotemporal dementia
	Christian Thomsen, PhD Vice President, Biological Research Lundbeck research USA, Paramus, NJ USA Title: Neuroprotective mechanisms of Rasagline for the treatment of Parkinson’s disease
	Wei-Qin Zhao, PhD.                          Scientist in the Dept. of Neurology Merck Research Laboratories, West Point, PA USA Title: Ab oligomer-induced synaptic loss via calcineurin-mediated endocytosis
	Yi Zhong, PhD Professor . Cold Spring Harbor Laboratory, Long Island, NY USA Title: Memory formation in Drosophila

Exhibitors are welcome to reserve their booth space early!

Please contact if you are interested in speaking in the scientific or Technology workshops of this meeting.

GeneExpression Systems, Inc.
P.O. Box 540170
Waltham, MA 02454 USA
Tel: (781) 891-8181
Fax: (781) 891-8234
E-mail: Genexpsys@expressgenes.com
www.expressgenes.com

Poster Abstract Submission by May 25, 2010

Abstracts

Title: Amyloid-beta: from Physiology to Pathology
Presenter name: Ottavio Arancio
Abstract:
Nanomolar levels of Alzheimer’s amyloid-b (Ab) impair long-term potentiation (LTP) and both spatial and fear memory. The effects of Ab, however, are not limited to disruption of synaptic function and memory. Low picomolar Ab increases LTP and memory. Depletion of Ab, in turn, impairs LTP and both spatial and contextual memory. We propose a model for the action of Aβ with positive and negative effects on LTP and memory representing a continuum, with low concentrations playing a positive and critical role resulting in normal plasticity and memory, and high concentrations playing a negative role resulting in reduced plasticity and memory.

Title: Use of Viral Vectors to Restore Hippocampal Synaptic Function in a Mouse Model of FRAGILE X SYNDROME
Presenter name: David C. Bloom
Abstract:
Fragile X Syndrome (FXS) is caused by a mutation that silences the Fragile X Mental Retardation gene (FMR1) which encodes the Fragile X Mental Retardation Protein (FMRP). To determine if FMRP replacement could rescue phenotypic deficits in an fmr1 knockout (KO) mouse model of FXS, we constructed an Adeno-Associated Virus-based viral vector that expresses FMRP. Using this vector we determined that FMRP replacement could rescue the fmr1 KO phenotype of enhanced long-term-depression (LTD), a form of synaptic plasticity linked to cognitive impairments associated with FXS. These results demonstrate the utility of viral-vector mediated protein replacement in the study of synaptic function in the CNS.  Potential applications and limitations of viral vector-mediated protein replacement in the CNS will be discussed.

Title: Potential therapeutic targets for Huntington’s disease: lessons learned from calorie restriction
Presenter name: Wenzhen Duan
Abstract:
Huntington’s disease (HD) is the most common inherited disorder affecting the nervous system in humans and is exemplary of polyglutamine repeat neurodegenerative diseases, and diseases caused by a single gene mutation. The HD gene encodes the protein huntingtin (Htt), whose polyglutamine expanison is believed to mediate the cytotoxic effects of HD, such as metabolic inhibition and neuronal loss.  Huntington’s disease serves a model for both neurodegenerative diseases and polyglutamine diseases. Currently, there is no cure or effective treatment that could delay the onset or slow the progression of HD.  Our laboratory aims to develop therapeutic approaches to treat HD. We found that calorie restriction (CR) retards the progression of neuropathological, behavioral, and metabolic abnormalities and extends survival in a mouse model of HD (Duan et al., PNAS 2003). To further dissect the neuroprotective mechanism(s) of CR, we found that neurotrophic factor BDNF and anti-aging molecular sirtuins, may play in important role in the neuroprotection. Using both genetic approach and chemical modifiers, we carried out experiments in models of HD to investigate the neuroprotective roles of BDNF and sirtuins. Our results suggest that SIRT1 and BDNF might be potential targets for developing therapeutics in HD, and other neurodegenerative disorders with similar mechanisms as well.

Title : Systems Biology of Plasticity at Inhibitory Synapses
Presenter name: Shin-ya Kawaguchi
Abstract:
Increase in intracellular Ca2+ concentration ([Ca2+]i) is critical for the induction of most forms of synaptic plasticity. However, the role of temporal pattern of the [Ca2+]i increase in regulation of synaptic plasticity remains elusive. Here, by combined application of systems biological model simulation and whole-cell patch clamp recording, I show that the temporal pattern of Ca2+ signal dynamically regulates whether the plasticity at GABAergic synapses is induced or not in a cerebellar Purkinje neuron . I also demonstrate an essential role of PDE1, a type of Ca2+-dependent phosphodiesterase, in the regulation of inhibitory synaptic plasticity by the context of Ca2+ signal.

Title: NMDA Receptor-Associated Cell Death Signals at Extra-Synaptic Sites
Presenter name: Youming Lu
Abstract:
N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extra-synaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292-1304 (NR2BCT). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2BCT that uncouples an activated DAPK1 from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca2+ influx through NMDA receptor channels at extra-synaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA receptor NR2B subunit at extra-synaptic sites and this interaction acts as a central mediator for stroke damage.

Title: Status and Future of Secretase Inhibitors
Presenter name: Patrick C. May
Abstract:
The Amyloid Cascade Hypothesis remains a key driver for drug discovery efforts directed towards Alzheimer’s disease. Blockade of Abeta production by secretase inhibitors offers a therapeutic intervention targeting the very top of this cascade. This presentation will briefly review the development and current status of gamma- and beta-secretase inhibitors in the clinic drawing data from Semagacestat , a molecule in Phase 3 trials for AD, to illustrate pre-clinical models and how these data translate to the clinic.  

Title: RNA regulation in human brain diseases
Presenter Name: Robert B. Darnell             
Abstract:
Dr. Darnell has pioneered translational studies of the paraneoplastic neurologic disorders (PNDs), disorders in which tumor immunity is linked to autoimmune brain degenerative disease.  He used PND autoimmune sera to identify the target antigens, leading to the discovery of several neuron-specific RNA binding proteins.  His work has combined genetic approaches with biochemistry and new methods development to study RNA regulation in vivo. These studies have discovered rules predicting brain-specific alternative splicing and alternative polyadenylation.  Recently the lab has developed HITS-CLIP, a precise means of pinpointing either protein-RNA or miRNA-mRNA regulatory sites and hence a means to understand the interactions regulating RNA expression. 

Title: Alzheimer’s disease: Taking STEPs to Improve Cognition
Presenter Name: Paul Lombroso
Abstract:
STriatal-Enriched protein tyrosine Phosphatase (STEP) is elevated in several neuropsychiatric diseases including Alzheimer’s disease, schizophrenia and fragile X syndrome. STEP dephosphorylates several key signaling proteins and inactivates them. The increased in STEP levels also leads to internalization of AMPA and NMDA receptors, which is thought to contribute to the cognitive deficits in these devastating illnesses. Results will be present of how genetic and pharmacological reduction in STEP activity reverses cognitive deficits in an animal model of Alzheimer’s disease.
 

Title: Epigenetic Mechanisms of Drug Addiction
Presenter Name: Eric Nestler
Abstract:
Eric Nestler will discuss the role played by changes in gene expression, and related changes in chromatin remodeling, in the brain’s reward circuits in mediating the long-lasting alterations induced by chronic exposure to drugs of abuse that underlie aspects of drug addiction. Particular attention will be given to two transcription factors of interest, CREB and ∆FosB, and to their numerous target genes and downstream functional consequences, as important mediators of drug action.

Title:  Visual Cycle Modulation as an Approach to the Treatment of AMD
Presenter Name: Ian L. Scott
Abstract:
This presentation will discuss the concept of visual cycle modulation as an approach to the treatment of Age-Related Macular Degeneration (AMD) and introduce ACU-4429, Acucela’s lead candidate for the treatment of this neurodegenerative disease.  ACU-4429 is an inhibitor of RPE65, which is the enzyme responsible for the isomerisation of all trans retinyl palmitate to 11-cis retinol and a key component of the visual cycle.  ACU-4429 is currently in Phase 2 trials for geographic atrophy.

Title: Role of spontaneous transmitter release in learning-related synaptic plasticity
Presenter Name; Robert D. Hawkins
Abstract:
Whereas short-term plasticity involves either pre- or postsynaptic modifications, long-term plasticity involves new synapse formation, which requires both.  What signaling molecules coordinate the pre- and postsynaptic changes, and when is that signaling first engaged?  We find that during short-term facilitation in Aplysia 5HT induces spontaneous transmitter release from the presynaptic neuron, which then recruits postsynaptic mechanisms of intermediate-term facilitation, including increases in AMPA-like glutamate receptors that may in turn induce new synapse formation during long-term facilitation.  Spontaneous transmitter release may play a similar role during synaptic plasticity in mammals, and could be involved in Alzheimer’s disease, schizophrenia, and addiction. 

Title:   Lineage-dependent neuronal circuit formation in the mammalian neocortex
Presenter Name: Songhai Shi
Abstract:
The concept of ‘functional column’ has cast a dominant influence on our understanding of the circuit organization of the mammalian neocortex. However, how to form functional neuronal circuits in columnar fashion with the precision of individual neurons is an outstanding question that remains largely a mystery. I will present our recent data showing that specific synapses preferentially form between radially aligned sister excitatory neurons that originate from the same progenitor cell in the rodent neocortex. This study suggests that the lineage relationship regulates the formation of precise neuronal circuits and functional columns in the mammalian neocortex.

Title: Neuroprotective mechanisms of Rasagiline for the treatment of Parkinson’s Disease
Presenter Name: Christian Thomsen
Abstract:
Rasagiline/Azilect is a potent, highly selective, monoamine oxidase type B (MAO-B) inhibitor. The symptomatic and disease-modifying effects of rasagiline in Parkinson’s disease (PD) are founded on its unique mechanism of action, which has been studied extensively in preclinical investigations. Mitochondrial dysfunction is a pivotal element in the complex pathogenesis of PD, and is central to apoptotic cell death. With relevance to PD, studies have shown that rasagiline can inhibit neurotoxin-induced loss of mitochondrial membrane potential, inhibit the release of cytochrome c, and induce pro-survival genes (Bcl-2, Bcl-xl) and neurotrophic factors (GDNF, BDNF) in vitro. Preclinical in vivo studies have similarly shown protective effects (behaviourally and biochemically) relevant to the pathogenesis of PD. These mechanisms may underlie the recently observed delay in disease progression in patients treated with Azilect (the ADAGIO trial).

Title: Memory formation in Drosophila
Presenter Name: Yi Zhong
Abstract:
We are interested in genetic dissection of memory formation in Drosophila. One of approaches we are undertaken is of studying genes identified in human neurogenetic disorders with a component of cognitive dysfunctions. We expect that such research may lead us to findings that bear more general significance at the molecular, cellular and even at the circuitry levels.  Currently, we are working on a range of models of disorders, including Alzheimer’s disease, neurofibromatosis type 1, Noonan syndrome, schizophrenia, and X-linked mental retardation. Among these studies, I will discuss specifically related to forgetting and the spacing effect of long-term memory formation.

Title: Phase 2 clinical trials of a novel neuroprotective drug, davunetide (AL-108) for the treatment of Alzheimer’s disease and frontotemporal dementia
Presenter Name: Alistair Stewart
Abstract:
Allon Therapeutics is developing a novel neuroprotective drug, davunetide (also known as NAP or AL-108) which has potential in the treatment of frontotemporal dementia, Alzheimer’s disease and other dementias. Davunetide was identified as a potent neuroprotectant in a range of in vitro and in vivo models. Davunetide has shown statistically significant effects in two Phase 2 clinical trials: amnestic mild cognitive impairment (aMCI) and schizophrenia-related cognitive impairment. The presentation will provide an update on the clinical development of davunetide and discuss the emerging thoughts on the need for trophic support to provide effective neuroprotection. 

Title: Cortical interneuron fate determination, and the generation of cortical interneurons from embryonic stem cells.
Presenter Name; Stewart Anderson MD
Abstract:
Cortical interneurons largely originate within a domain of the subcortical forebrain that expresses a key fate determining transcription factor, Nkx2.1. These cells play critical roles in cortical function and dysfunction through the actions of distinct subtypes. This presentation will discuss  recent advances from our lab in identifying molecular  determinants of interneuron subtype fate. In addition, we will present efforts to use this information to direct embryonic stem cells into cortical interneurons, together with implications of this work for studying interneuron related diseases and developing cell based therapy for seizures. 

Title: Rescuing prefrontal cortical gray matter in neuropsychiatric illness”
Presenter Name: Amy T. Arnsten
Abstract:
Mental illnesses such as bipolar disorder and schizophrenia involve dysfunction of the prefrontal cortex (PFC), the most evolved part of the human brain. The PFC provides “top-down” guidance of thought, action, and emotion through networks of pyramidal cell neurons that interconnect on dendritic spines. Disorders such as bipolar disorder and schizophrenia are associated with reductions in PFC gray matter, including loss of spines. Symptoms of bipolar disorder and schizophrenia are also worsened by stress exposure, e.g. a patient with bipolar disorder who is stable (euthymic) will often cycle into mania when exposed to stress. Research in the Arnsten lab for almost 30 years has shown that exposure to even acute, mild uncontrollable stress impairs PFC function in animals (Arnsten, Nat Rev Neurosci, 2009). This impairment involves high levels of catecholamine release in the PFC and an activation of cAMP and protein kinase C (PKC) signaling, leading to a reduction in PFC neuronal firing. With chronic stress, there is an additional loss of PFC dendritic spines (Radley et al, Cerb Cort, 2006), and more severe cognitive impairment (Liston et al, J Neurosci, 2006; Hains et al, PNAS, 2009). Spine density and PFC cognition can be rescued by chronic inhibition of PKC signaling (Hains et al, PNAS, 2009), possibly by preventing PKC phosphorylation of MARCKS and actin destabilization in spines (Calabrese and Halpain, Neuron, 2005). This finding is particularly relevant to bipolar disorder, where there are common genetic insults in PKC signaling pathways (e.g. DAG kinase; Baum et al, Mol. Psychiat, 2008), and common treatments such as lithium and valproate inhibit PKC signaling (Manji and Lenox, Biol Psychiat, 2009). These treatments are also able to rescue PFC gray matter (e.g. Blumberg et al, Biol Psychiat, 2006). This example provides a rational approach to the development of treatments for mental illness.

Title: Emerging mechanisms for schizophrenia aetiology: lessons learned from genomics.
Presenter Name: Dr Aiden Corvin
Abstract:
Schizophrenia and related disorders (including bipolar disorder) are common, substantially heritable brain disorders. Recent studies indicate that this involves both common and rare genetic risk variants. Identifying whether such variants map to specific molecular pathways is potentially critical in understanding the mechanisms of disease. Using a novel method of molecular pathway analysis we have identified evidence that common variants involved in cell adhesion molecule pathways contribute susceptibility to schizophrenia and bipolar disorder. These data will be presented in the context of ongoing investigations of rare variation and newer approaches, including whole genome sequencing will be considered.

Title: Ab oligomer-induced synaptic loss via calcineurin-mediated endocytosis
Presenter Name: Wei-Qin Zhao
Abstract:
Wei-Qin Zhao, Francesca Santini, Xiaohua Douglas Zhang, David J. Stone, Marc Ferrer, Abigail L. Wolfe, Paul J. Shughrue, and William J. Ray Merck Research Laboratories, West Point, Pennsylvania 19486,
Specific binding of Amyloid beta oligomers (ADDLs) to a subpopulation of neurons has been thought to contribute to synaptic impairments, an important feature of Alzheimer disease pathogenesis. In our current study, we have found that binding of ADDLs occurs at dendritic spines that express surface type II AMPA receptors (gluR2).  Interactions of ADDLs with these synapses trigger an endocytic process mediated by calcineurin, which is responsible for rapid internalization of bound ADDLs and surface AMPA receptors. The results support a model of disease pathogenesis in which Ab oligomers interact selectively with excitatory transmission, resulting in synaptic loss via facilitated endocytosis.