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Social Signal Transduction

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Social Signal Transduction Social regulation of gene expression Steve W. Cole, Ph.D. UCLA School of Medicine Division of Hematology-Oncology IL6 DNA Gene IL6 DNA Gene RNA IL6 DNA Gene Health RNA IL6 DNA Gene Early life social conditions S. Suomi 521 717 Mother reared Peer reared Health RNA IL6 DNA Gene Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Social signal transduction Social processes Genome Social signal transduction Social processes CNS function Genome Social signal transduction Social processes CNS function Peripheral neurobiology Genome Social signal transduction Social processes CNS function Peripheral neurobiology Cell signal transduction Genome Social signal transduction Social processes CNS function Peripheral neurobiology Cell signal transduction Transcription factors Genome Social signal transduction Social processes CNS function Peripheral neurobiology Cell signal transduction Transcription factors Genome Social signal transduction Social processes Simple questions CNS function Peripheral neurobiology Cell signal transduction Transcription factors Genome Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? Peripheral neurobiology Cell signal transduction Transcription factors Genome Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? 2. Which transcription control Peripheral pathways mediate those effects? neurobiology Cell signal transduction Transcription factors Genome Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? 2. Which transcription control Peripheral pathways mediate those effects? neurobiology 3. Which genetic polymorphisms modulate social influences? Cell signal transduction Transcription factors Genome Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? 2. Which transcription control Peripheral pathways mediate those effects? neurobiology 3. Which genetic polymorphisms modulate social influences? Cell signal transduction Transcription factors Genome ? Early life social conditions S. Suomi 521 717 Mother reared Peer reared Early life social conditions S. Suomi Inflammation Cell growth/differentiation Transcription control 521 717 Mother reared Peer reared Early life social conditions S. Suomi Inflammation Cell growth/differentiation Transcription control 521 717 Mother reared Peer reared Immunoglobulin production Type I interferon antiviral response Low SES Early life low SES Social threat Social loss / anticipated bereav ement Social instability Adolescent role incongruity Loneliness Introversion Acute stress Chronic stress Depression Sleep loss Social signal transduction Isolation Low SES Social threat Bereavement CNS function Peripheral neurobiology Cell signal transduction Transcription factors Genome CTRA – conserved transcriptional response to adversity Inflammation Cell growth/differentiation Transcription control 521 717 Mother reared Peer reared Immunoglobulin G1 production Type I interferon antiviral response CTRA – conserved transcriptional response to adversity Inflammation Cell growth/differentiation Transcription control 521 717 Mother reared Peer reared Immunoglobulin G1 production Type I interferon antiviral response CTRA – conserved transcriptional response to adversity Inflammation Cell growth/differentiation Transcription control 521 717 Mother reared Peer reared Immunoglobulin G1 production Type I interferon antiviral response CTRA – conserved transcriptional response to adversity Inflammation Cell growth/differentiation Transcription control 521 717 Mother reared Peer reared Immunoglobulin G1 production Type I interferon antiviral response hthate = btibacteria hthate = btibacteria loneliness = predation hthate = btibacteria loneliness = predation = bacteria hthate = btibacteria loneliness = predation = bacteria love = viruses Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? 2. Which transcription control Peripheral pathways mediate those effects? neurobiology 3. Which genetic polymorphisms modulate social influences? Cell signal transduction Transcription factors Genome Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? 2. Which transcription control Peripheral pathways mediate those effects? neurobiology 3. Which genetic polymorphisms modulate social influences? Cell signal transduction ? Transcription factors Genome Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Early life social conditions 521 717 Mother reared Peer reared Early life social conditions CREB / ATF EGR1, EGR3, EGR4/NGFIC NRF2 GATA 521 717 Mother reared Peer reared MAF, MZF1 ISRE, STAT1 Social Environment Health RNA IL6 DNA Gene Social Environment Health RNA IL6 DNA Gene Immune cell target of social adversity Transcript origin cell diagnostic Z-score p-value Monocytes .0001 Dendritic cells .1973 NK cells .2733 CD4+ T cells .9989 CD8+ T cells .9999 B cells .2609 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 Suomi results unpublished; method: Cole et al (2011) Proc Nat Acad Sci USA Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? 2. Which transcription control Peripheral pathways mediate those effects? neurobiology 3. Which genetic polymorphisms modulate social influences? Cell signal transduction Transcription factors Genome Social signal transduction Social processes Simple questions CNS 1. Which gene modules are function sensitive to social processes? 2. Which transcription control Peripheral pathways mediate those effects? neurobiology 3. Which genetic polymorphisms modulate social influences? Cell signal transduction Transcription factors Genome ? System properties Social processes CNS function Peripheral neurobiology Cell signal transduction Transcription factors Genome System properties Social processes CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors Genome System properties Social processes CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors Genome 2. Basal remodeling System properties Social processes CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors Genome 2. Basal remodeling System properties Social processes CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors Genome 2. Basal remodeling System properties Social processes CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors 3. Recursive persistence Genome 2. Basal remodeling SNS NGF LN Recursive developmental remodeling Body1 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Environment1 Body1 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Behavior1 Environment1 Body1 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Behavior1 Environment1 Body1 RNA1 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Behavior1 Environment1 Body1 RNA1 Body2 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Behavior1 Environment1 Body1 RNA1 Environment2 Body2 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Behavior1 Environment1 Body1 RNA1 Behavior2 Environment2 Body2 RNA2 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Behavior1 Environment1 Body1 RNA1 Behavior2 Environment2 Body2 RNA2 Behavior3 Environment3 Body3 RNA3 Cole (2009) Current Directions in Psychological Science Recursive developmental remodeling Behavior1 Time 1 Environment1 Body1 RNA1 Behavior2 Time 2 Environment2 Body2 RNA2 Behavior3 Time 3 Environment3 Body3 RNA3 RNA = intra-organismic adaptation Cole (2009) Current Directions in Psychological Science System properties Social processes CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors 3. Recursive persistence Genome 2. Basal remodeling SNS NGF LN System properties 4. Environmental recursion Social processes CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors 3. Recursive persistence Genome 2. Basal remodeling SNS NGF LN System properties 4. Environmental recursion Social processes Behavior CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors 3. Recursive persistence Genome 2. Basal remodeling SNS NGF LN System properties 4. Environmental recursion Social processes Behavior CNS function 1. Subjectivity Peripheral neurobiology Cell signal transduction Transcription factors 3. Recursive persistence Genome 2. Basal remodeling SNS NGF LN Recursive developmental remodeling Behavior1 Time 1 Environment1 Body1 RNA1 Behavior2 Time 2 Environment2 Body2 RNA2
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