2011 WSA Regional 2011 WSA Regional Conference Conference - - PowerPoint PPT Presentation

2011 WSA Regional 2011 WSA Regional Conference Conference

Creating the Dream: The Lifelong Journey with Williams Syndrome Salk Institute September 17th, 2011 Research Update 10:30-10:50am

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Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype Program Project NICHD HD03113-14 Ursula Bellugi, Director

Unlocking the Enigmatic Nature of Williams Syndrome

Characterization of Social Phenotype

Ursula Bellugi Salk Institute

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Modeling WS Using Human Neurons

Fred Gage Alysson Muotri Salk Institute

Cellular Architectonics

Katerina Semendeferi UC San Diego

Gene Networks for Social Cognition

Julie R. Korenberg Utah University

Hypersociability: New Perspectives from WS

Is anyone a stranger? Once more with feeling

Fascination with faces!!

ERP Biomarker: Increased Attention to ERP Biomarker: Increased Attention to Faces in WS Faces in WS

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ERP reflects increased response to happy faces, decreased to fearful faces in WS. Also in fMRI parallel study! Haas et al, 2009; Mills et al, 2006

New forays: What underlies WS social phenotype New forays: What underlies WS social phenotype

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Event Related Potentials (ERPs)

• Face paradigm, reward paradigm and trust paradigm

Psychophysiology

• Skin conductance response and heart rate simultaneously recorded to examine

autonomic responsivity to social and non-social stimuli, happy vs. scared faces

Visual Social Stimuli Visual Non-social Stimuli

Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype Program Project NICHD HD03113-14 Ursula Bellugi, Director

Unlocking the Enigmatic Nature of Williams Syndrome

Characterization of Social Phenotype

Ursula Bellugi Salk Institute

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Modeling WS Using Human Neurons

Fred Gage Alysson Muotri Salk Institute

Cellular Architectonics

Katerina Semendeferi UC San Diego

Gene Networks for Social Cognition

Julie R. Korenberg Utah University

What’s going on in Williams Syndrome brains when they see smiling faces? What What’ ’s going on in Williams Syndrome s going on in Williams Syndrome brains when they see smiling faces? brains when they see smiling faces?

Matt Erhardt Matt Erhardt Matt Erhardt

Williams Syndrome: A Model for Linking Genes, Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype Neural Systems, and Social Phenotype

Anders Dale Anders Dale Anders Dale Tim Brown Tim Brown Tim Brown University of California San Diego University of California San Diego University of California San Diego Eric Halgren Eric Halgren Eric Halgren

Genes Brain Structure and Function Social Phenotype Histology Stem Cells What are the cells like? Partial Deletions What do the genes do?

Brain Structure Brain Structure

(MRI) (MRI)

What parts of the brain make What parts of the brain make the Williams brain special? the Williams brain special? area

Left entorhinal Right occipital Right parietal Right medial orbital

Brain pathways Brain parts Brain surface

Brain Movies Brain Movies

(from MEG and MRI) (from MEG and MRI)

Are Williams brains Are Williams brains specially tuned to specially tuned to happy faces? happy faces?

sad neutral happy

Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype Program Project NICHD HD03113-14 Ursula Bellugi, Director

Unlocking the Enigmatic Nature of Williams Syndrome

Characterization of Social Phenotype

Ursula Bellugi Salk Institute

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Modeling WS Using Human Neurons

Fred Gage Alysson Muotri Salk Institute

Cellular Architectonics

Katerina Semendeferi UC San Diego

Gene Networks for Social Cognition

Julie R. Korenberg Utah University

Williams Syndrome and the Social Brain

Studies at the cellular level

Williams Syndrome Williams Syndrome and the Social Brain and the Social Brain

Studies at the cellular level Studies at the cellular level

Katerina Semendeferi, P.h.D

University of California San Diego

Katerina Semendeferi, P.h.D Katerina Semendeferi, P.h.D

University of California San Diego University of California San Diego

Brain Organization  Thinking and Emotions Analyze human brain tissue: Frontal Lobe and Amygdala

Laboratory of Human Comparative Neuroanatomy

Lisa Stefanacci Kari Hanson Nicole Barger

Brain Organization  Thinking and Emotions Analyze human brain tissue: Frontal Lobe and Amygdala

Branca Hrvoj Katerina Semendeferi

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• One of the most important steps from gene to behavior is how nerve

cells are connected to each other and develop into networks. This project will examine the cellular composition of the social brain and characterize the complexity of the neurons. There is more information for you on this project at the research table!

Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype Program Project NICHD HD03113-14 Ursula Bellugi, Director

Unlocking the Enigmatic Nature of Williams Syndrome

Characterization of Social Phenotype

Ursula Bellugi Salk Institute

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Modeling WS Using Human Neurons

Fred Gage Alysson Muotri Salk Institute

Cellular Architectonics

Katerina Semendeferi UC San Diego

Gene Networks for Social Cognition

Julie R. Korenberg Utah University

Modeling Williams Syndrome using human neurons

Recent advances

• Dr. Fred Gage
• Dr. Alysson Muotri
• Dr. Carol Marchetto

How to study WS Brain cells?

A new model for human condition?

Patient Control Are they Different? Brain Cells

The Tooth Fairy Kit Collection The Tooth Fairy Kit Collection

Proliferation of WS Brain Cells Proliferation of WS Brain Cells

9665 (Control) 5225 (typical WS) Day 0 Day 4

Proliferation of WS Brain Cells Proliferation of WS Brain Cells

WS Heart Cells

Can we find chemicals to help WS heart cells feels better?

Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype Program Project NICHD HD03113-14 Ursula Bellugi, Director

Unlocking the Enigmatic Nature of Williams Syndrome

Characterization of Social Phenotype

Ursula Bellugi Salk Institute

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Modeling WS Using Human Neurons

Fred Gage Alysson Muotri Salk Institute

Cellular Architectonics

Katerina Semendeferi UC San Diego

Gene Networks for Social Cognition

Julie R. Korenberg Utah University

Gene Networks for Social Cognition in Williams Syndrome

Julie R. Korenberg, MD, PhD Li Dai, PhD University of Utah

Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype

The Goal of Genetics in Williams syndrome To understand how specific genes disturb specific brain development and result in the positive and problematic social behavior and emotion in WS.

• Which WS genes are important for social behavior?
• Which WS genes are important for Neural Imaging such as MEG?
• How do the deleted genes change the interactions of the other 30,000 genes in WS?
• Are these genes active in the social brain regions?
• Can we find a way to alter the genetic disturbance and the behaviors in WS?

their brain,

Human: ~1.7meter Chromosome: 2-10 micrometer

Chr7

Genes deleted in WS

FKBP6

FZD9 BAZ1B BCL7B TBL2 WBSCR14 STX1A CLDN4 CLDN3 ELN LIMK1 WSCR1 RFC2 CYLN2 GTF2IRD1 GTF2I

What is different in Williams syndrome?

Typical WS Rare WS

From the person,

their behavior, their emotion,

to their genes

What do we do?

DNA/RNA √ Genes Proteins √ Cells √ Person √

Social behavior Brain function

Study genetics at many levels.

ELN LIMK1 FZD9 STX1A

GTF2I

FKBP6 GTF2IRD1 CYLN2

Typical Deletion 5889 Deletion

Dai Korenberg et al., 2008;

Reduced sociability in 5889:

• Reduced global sociability
• Reduced global approach
• Reduced approach strangers

A story of a little girl with WS and small deletion identifies a gene, GTF2I, contributing to sociability in WS

Recent advances: The different social and emotional behavior in WS come from differences in their genes.

Electrical and chemical contacts between neurons in brain Cells from blood Future: brain and neurons

Genetic pathway analysis

Circuits in brain

Brain synapse genes are different in WS

Recent advances

Hypothesis: WS region, social genes alter social neural pathways and then social behaviors Our current studies will reveal whether social brain hormones that affect trust and response to happy and fearful faces in controls, are changed in WS.

GENETICS

Neural Pathways ERPs Neuroimaging Emotion & Behavior

Sociability

Development WS Brain Expression Cellular Pathways

Genetics to understand behavior

Person to cells to DNA/RNA Multilevel studies

Neuroendocrine Social brain hormones

Future: use gene knowledge to help WS and to understand

• ther social disorders such as anxiety and autism.

Williams Syndrome: A Model for Linking Genes, Neural Systems, and Social Phenotype Program Project NICHD HD03113-14 Ursula Bellugi, Director

Meet the Team

Characterization of Social Phenotype

Ursula Bellugi Salk Institute

Neuroimaging of Social Circuitry

Eric Halgren UC San Diego

Modeling WS Using Human Neurons

Fred Gage Alysson Muotri Salk Institute

Cellular Architectonics

Katerina Semendeferi UC San Diego

Gene Networks for Social Cognition

Julie R. Korenberg Utah University

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The Paradox that is Williams Syndrome

• How can our children be hyper-social and not know how to effectively

socialize

• How can they be hyper-friendly and still have great difficulty making

friends

• How can they be hyper-communicative and have such a difficult time

making conversation

• Are our children better characterized as being hyper-social or hyper-

anxious? Have our children somehow been inherently blessed with the best defense for anxiety? And if they have – why does it sometimes stop working as they get older?

For years I have been asking questions - Brilliant scientists and leaps in technology are coming together beautifully to begin to put the answers within reach. We can help them get there!