DIRECTORY of

Developmental Researchers at Columbia University

College of Physicians and Surgeons

William Fifer, PhD - wpf1@columbia.edu

Perinatal Assessment of At-Risk Populations

The general research program is focused on the effects of fetal stimulation on brain/behavior development. Dr. Monk, a Sackler Fellow, together with Dr. Myers, Dr. Fifer and Dr. Sloan from the Department of Behavioral Medicine have expanded the research to include the influence of maternal emotional state on the fetus. They have been funded by March of Dimes and Narsad to investigate the associations between maternal depression and anxiety on fetal and infant development. Drs. Fifer and Myers have been funded to incorporate these approaches in a study of early markers of risk for Developmental Disorders and Sudden Infant Death (SIDS).

Department website :
http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/wpfifer.htm

Frederica P. Perera, Dr.Ph - fpp1@columbia.edu

Environmental health in Prenatal and Postnatal Infants: China, Poland and USA

Dr. Perera is conducting four different research studies in New York City , Poland , and China to determine the effects of prenatal and postnatal environmental exposures on fetal and child development. The exposures studied, include air pollutance (polycyclic aromatic hydrocarbons, diesel exhaust particles, and environmental tobacco smoke), and pesticides. These epidemiologic studies are combining environmental and personal monitoring, questionnaires, biomarkers, and clinical assessments following children through age 5. Interaction between environmental exposures and genetic polymorphisms, and nutritional deficits are being considered.

http://www.healthsciences.columbia.edu/dept/sph/ehs/15.html

Phil Grieve, PhD - pgg3@columbia.edu

Infant High Spatial Resolution EEG Imaging During Development

I am studying the spatial characteristics of EEG of the developing infant with a new high density EEG system with 128 leads. I have mathematically characterized this EEG collection system to quantify the error made in the spatial sampling of the EEG spatial waveform. It turns out that the infant requires more leads than the adult for the same spatial accuracy. I am working with a population of normal and sick infant subjects over the first year of life to determine the clinical utility of this method and to gain insight into its use for the study of neurodevelopmental pathologies

(e.g. SIDS).

Catherine Monk, PhD - cem31@columbia.edu

Woman's Moods During Pregnancy: Fetal and Infant Neurobehavior

We aim to understand if women's experiences of stress, anxiety, and depression have an impact on fetal and child development. Our subjects are pregnant women and their children - both during the fetal period and beyond.

http://nyspi.org/AR2001/behavioralmed.htm

Rakesh Sahni , MD - rs62@columbia.edu

Activity and Responses to Nutrient and Oxygen Supply during Development in Immature Human

Infants.

Using a bedside, miniaturized electroencephalography machine, he is able to monitor the brain waves of small infants during times of critical limitations in oxygen availability. Working in collaboration with researchers from the Department of Developmental Psychobiology, he has examined the effects of maturation and diet on state-related physiological variables of premature infants. He is also studying the effects of sleep position in developing low birth weight infants in an effort to understand the genesis of sudden infant death syndrome.

Department Website : http://cpmcnet.columbia.edu/dept/pediatrics/divisions/neo/fac.shtml

Karl F. Schultz, MD - kfs1@columbia.edu

The Effects of Hypoxia on the EEG during the first 72 hours of life

Dr. Schulze is primarily interested in neonatal bioenergetics. Energy expenditure, estimated by oxygen consumption and carbon dioxide production, is related to both fuel supply (diet) and to gas exchange (respiration). Also under study in this laboratory is a new and innovative system for physiological monitoring of the infant on mechanical ventilatory support and the effects of hypoxia on the EEG during the first 72 hours of life where major focus is on the development of states of sleep and wakefulness.

Department Website : http://cpmcnet.columbia.edu/dept/pediatrics/divisions/neo/fac.shtml

Raymond Stark, MD - Ris2@columbia.edu

Mechanism Underlying Fetal Vulnerability to Drugs and Nutrient Deprivation

The central theme of our neonatal Program Project Grant is based on the axiom that, during early stages of development, organisms are uniquely vulnerable to environmental challenges that constrain the physiological and behavioral phenotypes that are manifest throughout the rest of the life span of the organism. Understanding the mechanisms that confer risk or resistance to these challenges is the fundamental goal of the work done in all of the projects in this program. The program is composed of 3 projects and is served by 2 cores. In the first project Dr's Raymond Stark, Marianne Garland and Salha Daniel examine the risks conferred on the developing fetus by nicotine, a highly addictive and potent neuroactive drug whose potential for detrimental effects, at least in terms of the number of infants affected, is rivaled only by that of malnutrition in economically impoverished environments. In the second project Dr's Rakesh Sanhi, William Fifer, Sudha Kashyap and Karl Schulze, focus on nutritional challenges experienced by very low birth weight infants during their initial adjustment to extra-uterine life. Finally, other research address how nutrition and growth during early postnatal development serve to amplify effects of fetal programming.

Department Website : http://cpmcnet.columbia.edu/dept/pediatrics/divisions/neo/fac.shtml

2. CLINICAL/EPIDEMIOLOGICAL

Miron Baron, MD - mb17@columbia.edu

Molecular Genetics of Bipolar Disorder

An ongoing nationwide collection of pedigrees and cell lines as part of the “Healthy People 2000” initiative of the U.S. Public Health Service to assemble one of the largest genetic datasets for identifying genes for bipolar and related mood disorders. Also a continuing a systematic genome scan and studies of candidate chromosomal regions.

Department Website: http://nypisys.cpmc.columbia.edu/AR2002-03/divs/MedGen-c.html

Alan S. Brown, MD - asb11@columbia.edu

Prenatal Etiologies of Schizophrenia

We aim to examine the relation between prenatal exposure to infection, nutritional deficiencies, toxins, hormones and other factors to schizophrenia. In addition, we seek to investigate interactions between these prenatal exposures and genetic polymorphisms to risk of schizophrenia. These include studies derived from two birth cohorts. The first is the Prenatal Determinants of Schizophrenia Study, derived from a cohort of over 19,000 pregnancies; among them, 71 cases of schizophrenia and other schizophrenia spectrum disorders have been diagnosed. The second is the Columbia Rubella Study, consisting of nearly 70 subjects prenatally exposed to rubella, in whom we have demonstrated a markedly increased risk of schizophrenia and other spectrum disorders. Unlike most previous studies of prenatal factors of schizophrenia, our work makes use of serologic and clinical confirmation of prenatal exposures.

Department Website: http://nypisys.cpmc.columbia.edu/AR2002-03/divs/EpiofBrainDis-c.html

Susan Coates , PhD - swc1@columbia.edu

Intervention Programs and the Parent-Infant Relationship

The Parent Infant Program, under the auspices of Susan Coates, Ph.D. as Director, is designed to offer services to families of children under three. This program is composed of two components: the Parent Infant Psychotherapy Training Program, and the Research Unit. The research unit, still in its early stages, is hoping to study the impact of our programs on the parent infant relationship .

Department Website: http://www.columbiapsychoanalytic.org/index.html

Cheryl Corcoran, MD - cc788@columbia.edu

The widely held assumption that psychosocial stress and life events can trigger psychosis in vulnerable individuals has never been tested in a rigorous prospective study design. A measure exists now that can identify a prodrome for psychosis in adolescents and young adults with 40-50% accuracy over 1 to 2 years. Our study is a 2-year longitudinal evaluation of 60 individuals identified as prodromal to psychosis with baseline and periodic assessments of symptoms, cognition. psychosocial stress, and salivary cortisol measures.

Department Website: http://nypisys.cpmc.columbia.edu/AR2002-03/divs/MedGen-c.html

Lawrence L. Greenhill, MD - GREENHIL@CHILDPSYCH.COLUMBIA.EDU

Preschool ADHD Treatment Study

The PATS Study is a three-year, 6-site cooperative NIMH project to determine the safety and efficacy of methylphenidate in preschool children, ages 3 to 5.5, with Attention Deficit Hyperactivity Disorder.

Department Website : http://childpsych.columbia.edu/s_center_2.html

Mandy Hornig , MD - mh2092@columbia.edu

My research program focuses on understanding the interactions of microbial, immune, toxic, traumatic, and other environmental influences with the genetic and developmental context of the host, and their relationship to the pathogenesis of neuropsychiatric disorders. Using behavioral, biochemical, immune, and neuropathologic approaches, this work integrates data from animal models of pre- and postnatal microbial, immune, or toxic neural injury with findings derived from studies of clinical populations (subjects with autism spectrum disorders, attention deficit/hyperactivity disorder, schizophrenia, affective disorders) in an effort to define the basis of vulnerability to neurodevelopmental damage and devise new strategies for prevention, early detection, or remediation of neuropsychiatric disorders.

Department Website: http://chaos.cpmc.columbia.edu/sphdir/pers.asp?ID=717

L. Erlenmeyer-Kimling, PhD - le4@columbia.edu

A Prospective Study of Children of Schizophrenic Parents

This longitudinal., prospective study which began in 1971, follows offspring of schizophrenic, effectively ill and psychiatrically normal parents. Deficits in at least 3 neurobehavioral measures (verbal short-term, memory attention, and gross motor skills) tested in med-childhood are strong predictors of adulthood schizophrenia-related psychoses in offspring o schizophrenic parents and may be indicators of the schizophrenia genotype. Ongoing work attempts to differentiate patterns of other childhood characteristics in children with these neurobehavioral deficits, comparing subjects who developed schizophrenia-related psychoses versus those who did not. Ratings of parental interviews and videotaped interviews of the offspring suggest that specific childhood behaviors and negative symptoms may also predict later schizophrenia, whereas adolescent event related brain potentials may predict later negative symptoms.

Department Website: http://nypisys.cpmc.columbia.edu/AR2002-03/divs/MedGen-c.html

James Knowles, MD - jak8@columbia.edu

Genetic Mechanisms in Developmental Disorders

The lab continues collaboration with Dr. Jane Morse on determining how mutations in the bone morphogenetic protein receptor 2 gene cause the disorder. Studies of several candidate genes for panic disorder have recently been published (collaborating with Drs. Weissman, Hodge and Fyer). One of these, catechol-O-methyltransferase, appears to play a role in the development of the disorder. Work on AD continues (collaborating with Dr. Richard Mayeux), with the finding of a potential gene on chromosome 12 that predisposes individuals of Caribbean Hispanics descent to the disorder.

Department Website: http://nypisys.cpmc.columbia.edu/AR2002-03/divs/MedGen-c.html

Dolores Malaspina - dm9@columbia.edu

Genetic and environmental factors and their interaction In Vulnerability to Schizophrenia

The group continues to examine genetic and environmental factors and their interaction with respect to the liability to schizophrenia. Further analyses continues on data from a birth cohort in Jerusalem , in which Dr. Malaspina had previously identified a significant effect of paternal age on risk for schizophrenia. In the past year, this study has been supplemented by awards from NIMH to collect DNA samples of study participants and from NARSAD to examine “de novo mutations.” The study was also recognized in the New York State Office of Mental Health Research Award, given to Dr. Malaspina in fall 2001.

Department Website: http://nypisys.cpmc.columbia.edu/AR2002-03/divs/MedGen-c.html

Bradley Peterson, MD - petersob@childpsych.columbia.edu

The Application of Neuroimaging Methodologies to the Study of Childhood Neuropsychiatric Disorders

Pathological conditions that have been the focus of my imaging studies include Tourette syndrome, Obsessive-Compulsive Disorder, Attention-Deficit/Hyperactivity Disorder, Bipolar illness,
pre-term birth, and Schizophrenia. I have worked extensively on the development of functional MRI paradigms, with a primary interest in the study of attention, impulse control, and top-down information processing in the central nervous system.

Department Website : http://childpsych.columbia.edu/s_faculty_01.html

http://childpsych.columbia.edu/brainimaging/

B. Timothy Walsh , MD - btw1@columbia.edu

Mechanisms for the Development of Eating Disorders

This unit conducts clinical research on the eating disorders: anorexia nervosa, bulimia nervosa and binge eating disorder. Studies range from investigations of underlying biological and psychological mechanisms to the development of treatment methods.

Department website : www.eatingdisordersclinic.org

Myrna M. Weissman, PhD - mmw3@columbia.edu

Families at High and Low Risk for Depression

The overall aim has been to understand the long-term, temporal sequence and familial patterns of psychiatric and behavioral problems from childhood to adulthood in offspring at high and low risk for depression. This study has had 5 waves of assessments and 3 generations and began nearly 20 years ago. A current aim is to define the neural correlates of familial risk for depression in subjects in the 2 nd and 3 rd generations of this cohort using anatomical and functional MRI. EEG and startle data on the 2 nd and 3 rd generations have also been collected.

Molecular Genetic Studies of Fear & Anxiety

A Program Project Grant in collaboration with E. Kandel, C. Gilliam, R. Hen and A. Fyer began in 2003. The aim is to understand the genetic basis for fear and anxiety disorders in humans by identifying variant forms of genes that may contribute to pathological anxiety states. The underlying idea is that both learned and innate fear are tractable targets for genetic analyses in mice and humans. To accomplish the aim dealing with human anxiety disorders we will provide well characterized clinical samples and DNA from subjects with panic and social anxiety disorder and controls.

Department Website : http://nypisys.cpmc.columbia.edu/AR2002-03/divs/clin&genepi-c.html

3. DEVELOPMENTAL BEHAVIORAL NEUROSCIENCE

Gordon A. Barr,PhD - gbarr@hunter.cuny.edu

" Opiate Dependence and Tolerance; Nociception and Analgesia"

T he general topic of study by this lab is how the development of neural and other physiological processes result in behavioral and physiological maturation. To that end, we study behavior within a developmental framework and examine how the maturation of biological systems might cause those changes. This approach lends itself to the use of a variety of behavioral, anatomical, pharmacological, and genetic methods, all of which are brought to bear on the biological question of interest. Currently we are studying ontogenetic differences in gene expression during withdrawal using gene microarrays. These studies will provide a profile of the changes in gene expression induced by chronic opiates during ontogeny.

Department Website : http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/gbarr.htm

Susan Brunelli, PhD - sab9@columbia.edu

" Genetic Basis of Separation Anxiety"

E pidemiologic studies suggest the inheritance of depression and anxiety disorders across generations, and developmental stability of anxiety behaviors in offspring of affected parents. Such children and adults exhibit profiles of altered autonomic nervous system (ANS) regulation, augmented hypothalamic-pituitary axis (HPA) activity, and greater sympathetic drive. To examine both inherited and developmental influences on anxiety, this laboratory has produced three lines of rats selectively bred for extremes of ultrasonic vocalization (USV) to separation and isolation in infancy (High, Low and Random USV Lines). High USV line rats show more behavioral reactivity to novelty in infancy and in adulthood.

Department Website : http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/sabrunelli.htm

Jay Gingrich, MD, PhD - jag46@columbia.edu

Transgenic and Knockout Mouse Models to Study the Molecular Mechanism for Vulnerability to

Schizophrenia and Depression

We are using mice as models to investigate the role of specific genes in the development of neuropsychiatric disorders such as schizophrenia and depression. Our strategy utilizes the transgenic and knockout technology to generate these models and an integrated assessment of behavior, biochemistry, and molecular biology to better understand the impact of these genetic lesions on developmental outcomes.

Department Website - http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/jagingrich.htm

Joseph A. Gogos, MD, PhD - jag90@columbia.edu

"Assembly and Maintenance of Sensory Maps in the Brain; Animal Models for Genes Predisposing to Psychiatric Disorders"

We are using powerful techniques that permit us to control the survival and synaptic transmission of specific subsets of olfactory neurons in a temporally and spatially regulated manner, to investigate a) how precise connections between the periphery and the brain are continually maintained to preserve the integrity of the olfactory sensory maps, b) to examine whether there is modularity in the assembly of these maps and c) to probe the role of activity-dependent plasticity in the establishment, maintenance, and refinement of the olfactory sensory projections.

We are also collaborating with Dr. Karayiorgou's lab at Rockefeller University to follow-up genetic findings from families afflicted with schizophrenia and other psychiatric disorders, by generating transgenic mouse lines for candidate susceptibility genes in order to a) strengthen or weaken our hypotheses for a role of these genes in disease susceptibility and b) facilitate understanding of the function of these genes and how they may impact on the development of psychiatric disorders

Department Website : http://cpmcnet.columbia.edu/dept/neurobeh/nb_faculty.html

Rene Hen, PhD - rh95@columbia.edu

"Genetic Models of Anxiety and Depression"

We are using genetically engineered mice to study the circuits and molecules that underlie emotional behavior.

SEROTONIN RECEPTORS AND BEHAVIOR - Serotonin (5HT) is involved in a wide range of behaviors, and serotonergic drugs are used in the treatment of pathological states such as depression, appetite disorders, and migraines. Pharmacological studies and molecular cloning have identified several subtypes of receptors with distinct pharmacological properties, signaling systems, and tissue distributions. The study of the function of individual serotonin receptor subtypes has been hampered by the lack of specific drugs. In addition, a number of the serotonergic drugs that are active in the treatment of neuropsychiatric disorders influence the whole serotonergic system. For example, antidepressants such as fluoxetine (Prozac) are 5-HT uptake blockers, however. To dissect the contributions of individual serotonin receptors to physiology and behavior, we have created mouse mutants lacking individual receptor subtypes. These mice provide genetic models for a number of human behavioral traits such as: impulsiveness, depression, and vulnerability to drugs of abuse. The neural circuits underlying these traits are currently under investigation.

Department Website : http://cpmcnet.columbia.edu/dept/neurobeh/nb_faculty.html

Myron A. Hofer, MD - mah6@columbia.edu

"Processes of Attachment and the Regulation of Development"

O ur research has centered on the role of the parent-infant relationship as the first major environmental influence on postnatal development. I and my colleagues have explored how early maternal separation and different patterns of mothering exert long-term effects on vulnerability to disease. Through an experimental analysis of the psychobiological events that enmesh the infant rat and its mother, he discovered hidden regulatory processes that have become the basis for a new understanding of the early origins of attachment, the dynamics of the separation response and the shaping of development by that first relationship.

Department Website : http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/mahofer.htm

Sanjay J. Mathew, MD - sjmathew@hotmail.com

"Neuroimaging Studies of Adversely Reared Non-Human Primates Undergoing Variable Foraging Demand in Infancy"

Our goal is to use volumetric MRI, proton magnetic resonance spectroscopic imaging, and diffusion tensor imaging (DTI) in bonnet macque primates to compare the long-term neuroanatomical substrates underlying early developmental traumatic experiences with those raised under normal laboratory conditions. We are collaborating with the SUNY Primate Behavioral laboratory in Brooklyn .

Holly Moore, - hm2035@columbia.edu

In general the goals of developmental studies in my laboratory are to determine the effect of an early disruption of DAN methylation in the developing cortex on adult behaviors that in the normal animal, depend upon limbic and prefrontal cortical circuits. In these studies we administer the DNA methylating agent methylazoxymethanol acetate to the pregnant rat dam at a dose(20-25mg/kg) and Gestational period (GD17-18) that results in a disruption of development and resultant thinning primarily in limbic and paralimbic cortices. Adult offspring of MAM-treated dams have no discernable sensorimotor deficits but do have deficits in behaviors known to depend on hippocampal-striatal and prefrontal cortical projections. The pattern of behavioral deficits and pattern of cortical thinning and changes in cell packing density may be a useful and valid model for relationships between the neuro- and psychopathology of schizophrenia. Future studies with this model will closely examine the behaviors, neuroanatomy, neurochemistry and cortical electrophysiology or MAM-exposed rats across development.

Methods used: 1) Behavioral tests including prepulse inhibition, fear potentiated startle, maze tasks, attentional and memory tasks in operant boxes. 2) in vivo microdialysis and HPLC for monoamine and amino acid neurotransmitters. 3) In vivo single-cell electrophysiology, in anesthetized rodents.

Department Website : http://cpmcnet.columbia.edu/dept/neurobeh/Moore.html

Michael Myers, PhD - mmm3@columbia.edu

"Early Nutritional Influences on Vulnerability to Disease"

The search for mechanisms that underlie the transduction of early experience is a focus of much of the work in our department. In one area, animal studies conducted in this laboratory have shown that certain adult characteristics can be influenced by specific types of mother/infant behavioral interactions associated with feeding in infancy. In collaboration with researchers at Newark Beth Israel Hospital , we are now pursuing the question of how key aspects of the pre- and postnatal environments may influence the expression of these important interactions in human infants. Most recently, we have initiated a new series of animal studies in collaboration with investigators in the Department of Pediatrics to study the long-term effects of pre- and postnatal nutrition on metabolic and neurobehavioral disorders.

Department Website : http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/mmyers.htm

Jonathan Polan, MD - jpolan@mail.med.cornell.edu

In the Kandel lab I joined a group that is creating genetically engineered mouse models of schizophrenia, animals with selective dysfunctions of the dopamine or glutamate systems limited to the striatum or neocortex, the neurotransmitters and brain regions implicated in schizophrenia. Because of strong evidence that schizophrenia is a neurodevelopmental disorder, we focussed on the developmental aspects of these animals' phenotypes using a molecular switch to turn the transgenes off during specific developmental windows. For the academic year 2004-05 this project is being funded by the Sackler Research

Department Website : http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/hjpolan.htm

Daniel Schechter, MD - dss11@columbia.edu

Department Website:

http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/dsschechter.htm

Harry Shair, PhD - hns1@columbia.edu

"Formation and Influence of Early Social Relationships"

D r. Shair's interest is in determining how the early environment, pre- or postnatal, contributes to ontogenetic course of the growing organism. Much of his work has focused on the influence of the parent-infant interaction on postnatal development. His most recent work has addressed the mechanisms by which the earliest social bonds are formed (see Social potentiation, below). While never ignoring the primary importance of behavior, Dr. Shair also investigates the physiological mechanisms underlying behavior in studies of the cardiovascular system, respiratory regulation, and sleep/wake states. Other areas of research have included the impact of early denervations, malnutrition, and genetic interactions with environmental effects. Collaborations within the department have been with Dr. Hofer, Dr. Brunelli , and Dr. Myers.

Department Website:

http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/hnshair.htm

Mark Underwood, - undie@neuron.cpmc.columbia.edu

Developmental abnormalities in the serotonergic system contributing to suicidal behavior.

We have found enduring alterations in the serotonergic system in the brain of suicide victims postmortem. Studies are being conducted in transgenic mice, monkeys and postmortem human brain examining neurodevelopment of the serotonergic system in brain and the relationship to individual differences in behavior. Serotonergic neurotransmission is examined using quantitative anatomical measures including stereology, autoradiography and immunocytochemistry.

Department Website: http://nypisys.cpmc.columbia.edu/AR2002-03/divs/Neuroscience-c.html

Christoph P. Wiedenmayer, PhD - cpw14@columbia.edu

" Early Stress: From Brain to Behavior"

We investigate the endocrine and behavioral responses to threat in young animals and how these responses change during the first couple of weeks of life. An ethological approach provides a framework to describe and analyze behavioral responses to ecologically salient stimuli. A neurobiological approach guides the investigation of the neural substrates that underlie endocrine and behavioral responses to threat. An ontogenetic approach helps to explain these changes in brain and behavior during the different stages of development.

Department Website: http://nypisys.cpmc.columbia.edu/DevelopmentalPsych/sections/research/cpwienmayer.htm

Jane Dodd, PhD., Professor - jd18@columbia.edu

"Neural Differentiation and Axon Guidance in the Vertebrate Central Nervous System"

We are studying the molecular and cellular events that regulate the early development and organization of the central nervous system. After neuronal differentiation, axons extend towards their target cells within the central nervous system, navigating under the guidance of cues in the environment. To determine the nature of such cues and the mechanisms by which growth cones respond to them, we have analyzed the earliest axonal pathways in the developing spinal cord. Two groups of cells, located at the dorsal and ventral midlines and known as the roof plate and the floor plate, respectively, appear to act as sources of cues for commissural axons. The ventral midline of the neural tube consists of several subgroups of cells that differ, according to their position in the rostro-ca da` ahaa$ h, 0 ap``d`aigh -" " hd5 @B 2 `b` aaed `ifc *, ! ac,  "" f`aed p`a ``)" ``ae be`da ! @E db ``4 4 bb`ea ad phe 0 bnhb% (& `bald `a`h d9 " `b` a`ob`$ "B `n de 1 0 8 (`baae pb$ `d``.` a l id%"DADP `p`id d`d b% ba pabe da `!"d db`dc`` ha`ahdd d`` " hd0 DDD"& 4b`` e ``a, `eld `pm b A5"BEDP `pa`a`ebda !"d rabddd `d `e m" eapdab iddh4 a``gh hd e`p- " )d%"@FD@ ( $ b`ala`a  $b``d cr`0" `a$``l d`ed1 @NDDH c``b```db)"@D n bd `he `d1 BNPDM"  ,%```he`a`,$,dr de at"0hgf``a$ <,`. ,` `h($.,"d``d "0#( ad8p>

Mechanisms of Neuronal Differentiation and the role of growth factors .

The overall aim of our research is to understand the steps and decision processes involved in converting immature precursor cells into mature neurons. To this end, we have developed and exploited a cell line (designated PC12) that serves as a powerful model for neuronal differentiation. Specifically, the defined neurotrophic agent nerve growth factor (NGF) causes PC12 cells to switch from a dividing neuroblastic phenotype to a non-dividing, neurite-bearing phenotype which resembles that of a mature sympathetic neuron. To understand the steps involved in this conversion, we have undertaken a variety of studies to compare the cells before, and at various times after, their exposure to NGF

Department Website: http://www.cumc.columbia.edu/dept/neurobeh/Greene_center.html

James E. Goldman, - jeg5@columbia.edu

Developmental neurobiology, particularly cell lineages and the regulation of developmental fates; The nature of progenitor cells in the adult CNS

We are tracing cell lineages in the developing mammalian CNS to study the origins of astrocytes and oligodendrocytes from immature neuroectodermal cells. Using retroviral mediated gene transfer, we are following the migration and differentiation of immature cells of germinal zones in vivo and have determined that there are time- and location-specific patterns of glial development. We are examining what roles
environmental vs. lineage-controlled factors play in specifying cell fate. We have also been investigating the nature of cycling cells in the adult mammalian CNS, characterizing their phenotypes and their fates under normal and pathological circumstances, finding that these can generate oligodendrocytes during remyelination and both glia and neurons in cell culture .

Department Website : http://cpmcnet.columbia.edu/dept/neurobeh/nb_faculty.html

Thomas Jessell, PhD - km219@columbia.edu

Molecular Genetic Specification of Developing Neuronal Circuitry

Research in the laboratory attempts to define mechanisms that specify the identity of neurons, the patterning of their axonal projections, and the formation of selective synaptic connections. We study these problems in the vertebrate central nervous system, with an emphasis on neurons that contribute to the spinal monosynaptic reflex circuit. This neuronal network is comparatively simple and is evolutionarily conserved and forms in an activity-independent manner, suggesting that its assembly is genetically encoded.

Laboratory Website: http://cpmcnet.columbia.edu/dept/neurobeh/jessell/

Richard Mann, PhD - rsm10@columbia.edu

Control of pattern formation by homeotic genes and their downstream targets in Drosophila

The Hox genes encode homeodomain transcription factors that are important for specifying tissue and cell-type identities, usually in discreet regions along the anterior-posterior (A-P) axis, of many animals. These genes are well conserved throughout metazoans. Moreover, changes in the way Hox proteins regulate their target genes has likely played an important role in the diversification of animal morphologies during animal evolution. Therefore, knowledge of how these proteins function at a mechanistic level is critical for understanding normal animal development, many human developmental disorders, and animal evolution.

The homeodomain is a DNA binding motif that, on its own, has loose DNA recognition properties. This question is especially relevant to the Hox proteins, because their homeodomains are highly similar, especially in the residues known to contact DNA. One question, then, that the lab has been interested in for several years is how these proteins achieve specificity in vivo.

Department Website : http://www.cumc.columbia.edu/dept/gsas/biochem/

Lab Website : http://www.cumc.columbia.edu/dept/gsas/biochem/labs/mann/index.html

Carol A. Mason, PhD, Professor - cam4@columbia.edu

Cell-Cell Interactions in the Developing Brain

The primary aim of our research is to understand the mechanisms that underlie axon growth and the formation of specific synaptic connections. We use a battery of static and dynamic morphological approaches in intact brain and in tissue culture . To study axon navigation through pathways, we examine the formation of bilateral projections in the mouse visual system. Our focus is the optic chiasm, a classic example of a "decision region" where fibers from each retina re-sort before traveling to targets on each side of the brain. By dye labeling axons, recording their morphology and behavior in real time, and using immunocytochemistry, we have observed that retinal axons diverge upon meeting a novel midline specialization composed of immature neurons and glia. In vitro and molecular approaches are being used to identify the cellular and molecular cues at this site that direct retinal axon divergence, and the mechanisms underlying specification of retinal ganglion cells to respond to these cues.

Department Website : http://cpmcnet.columbia.edu/dept/neurobeh/Mason_center.html

Peter Scheiffele, PhD - ps2018@columbia.edu

Molecular Mechanisms of Synapse formation in the CNS

We are interested in the cell-biological mechanisms that lead to the formation of pre- and postsynaptic membrane specializations during development of the central nervous system. Moreover, we are studying signaling events that control the specificity of synapse formation. To achieve these goals we are using a combination of cell-based in vitro assays, functional imaging, biochemistry, and gene expression profiling.

Department Website : http://cpmcnet.columbia.edu/dept/neurobeh/nb_faculty.html

Ann-Judith Silverman, PhD - as36@columbia.edu

Cellular immigration into the central nervous system

There are two populations of cells under study in my laboratory: one neuronal, and one involved in inflammatory responses. The neuronal population makes the neuropeptide, gonadotropin releasing hormone (GnRH), which is essential for normal reproductive development. These cells originate in the olfactory placode and migrate broadly within the CNS during early embryogenesis. Our goal is to understand the mechanism by which these cells find their way to their various target sites in the CNS. The laboratory uses both in vivo and in vitro methods to alter the microenvironment of the migrating cells to determine what might promote or hinder movement. In addition, experiments with video confocal microscopy of labeled slices will also be used to analyze this movement mechanistically .

Department Website : http://cumc.columbia.edu/dept/gsas/anatomy/Faculty/Silverman/

Dominique Toran- Allerand, MD, ScD - cdt2@columbia.edu

Estrogen Action in the Developing Brain

The long-term goals of the research in my laboratory are to understand the cellular and molecular mechanisms underlying the growth or neurite-promoting properties of estrogen, which I first described in organotypic slice cultures of the developing rodent hypothalmus, preoptic area and neocortex. My current studies investigate some novel forebrain neuron that subserve cognitive functions.

Department Website : http://cpmcnet.columbia.edu/dept/neurobeh/nb_faculty.html