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Principal Investigator: Barbara Hirschman Chaiyachati
Organization: CHILDREN'S HOSP OF PHILADELPHIA
Fiscal Year: 2024
Award: $181,186
Funding agency: National Institute of Mental Health
Project Summary/Abstract
This career development award details a 5-year training plan to facilitate the transition of Dr. Barbara H.
Chaiyachati to an independent career as a physician-scientist studying predictors of mental and physical health
of children after trauma with an objective to identify actionable targets of intervention. Experiences of child
abuse and neglect place hundreds of thousands of children at risk for negative health outcomes every year in
the U.S. Better understanding of proximate mental and physical health predictors after childhood traumatic
stressful events (TSE), including predictive role of genetic susceptibility integrated with early biologic
embedding by epigenetic age acceleration (EAA) and increased inflammation, may facilitate targeted
interventions to ameliorate the spectrum of long-term health burdens. Thus, multimodal phenomic and genomic
approaches are needed to elucidate the complex connections between maltreatment and health. The proposed
project builds on the diverse clinical and research experiences of the candidate, with mentorship led by Dr.
Raquel Gur, the Karl and Linda Rickels Professor of Psychiatry, Neurology and Radiology at the University of
Pennsylvania and an expert in neurodevelopmental trajectories, and Dr. Hakon Hakonarson, Professor of
Pediatrics at the Children’s Hospital of Philadelphia and an expert in translational genomics. A team of
collaborators adds expertise in developmental psychology, basic and clinical immunology, psychiatric genetics,
and behavioral epigenomics, with grounding in child abuse clinical care. The research leverages large,
ancestry-diverse, adversity-exposed cohorts within established biorepositories to identify measurable,
biologically-relevant health predictors after adversity in childhood. Dr. Chaiyachati will conduct phenomic
(physical, mental health, systemic inflammation by cytokines) and genomic (whole genome and methylome)
assessments. Specifically, Aim 1 is to determine the impact of TSEs and genetic stress sensitivity, as marked
by genetic risk for PTSD, on mental and physical health in adolescence; Aim 2 will assess the impact of TSE
on epigenetic aging per DNA methylation clocks; and Aim 3 will test for increased inflammation after
experiences of maltreatment. Completion of the proposed studies will improve our understanding of mental and
physical health trajectories after experiences of trauma. This proposal will also provide the candidate with
experience studying phenomic and genomic data, writing grants and scientific papers, and allow her to gain
skills requisite for supervision and leadership. Furthermore, this proposal will establish Dr. Chaiyachati’s
intersectional research agenda and position her for independence as a physician-scientist.
Terms: <0-11 years old><12-20 years old><21+ years old><Abate><Accounting><Address><Adolescence><Adult><Adult Human><Age><Attention><Award><B-Cell Differentiation Factor Gene><B-Cell Stimulatory Factor 2 Gene><BSF-2 Gene><BSF2 Gene><Behavioral><Beta-2 Gene Interferon><Biological><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Child><Child Abuse><Child Abuse and Neglect><Child Health><Child Welfare><Child Youth><Childhood><Childhood Abuse><Childhood maltreatment><Children (0-21)><Children's Hospital><Clinical><Clinical Immunology><Complex><DNA Methylation><Data><Development><Diagnosis><Diagnostic><Differences between sexes><Differs between sexes><Dimensions><Dose><Emotional><Environment><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epigenetic age><Funding><Future><Gene x Environment Interaction><General Radiology><Genes><Genetic><Genetic Predisposition><Genetic Predisposition to Disease><Genetic Risk><Genetic Susceptibility><Genetic propensity><Genomic approach><Genomics><Goals><Grant><GrimAge clock><Gur><GxE interaction><HSF Gene><Hannum clock><Health><Hepatocyte Stimulatory Factor Gene><Horvath clock><Hybridoma Growth Factor Gene><IFNB2 Gene><IL-6 Gene><IL6><IL6 gene><Immunology><Inflammation><Inflammatory><Inherited Predisposition><Inherited Susceptibility><Interleukin 6 (Interferon, Beta 2) Gene><Interleukin-6 Gene><Intervention><Intervention Strategies><Investigators><K-Awards><K-Series Research Career Programs><Leadership><Long-term prospective studies><Longterm prospective studies><Measurable><Measures><Medical><Mental Health><Mental Hygiene><Mentorship><Methylation><Modernization><Morbidity><Morbidity - disease rate><Neurology><Outcome><PTSD><Paper><Pediatric Hospitals><Pediatric Research><Pediatrics><Pennsylvania><PhenoAge clocks><Phenotype><Philadelphia><Physicians><Policies><Population Heterogeneity><Position><Positioning Attribute><Post-Traumatic Neuroses><Post-Traumatic Stress Disorders><Posttraumatic Neuroses><Predisposition><Psyche structure><Psychiatry><Psychological Health><Psychopathology><Radiology><Radiology Specialty><Reporting><Research><Research Career Program><Research Personnel><Researchers><Risk><Role><Sampling><Scientist><Sex Differences><Sexual abuse><Sexual differences><Stress><Stressful Event><Supervision><Susceptibility><Testing><Training><Translational Research><Translational Science><Trauma><Universities><Work><Writing><abnormal psychology><accelerated epigenetic age><accelerated epigenetic aging><accelerated pace of epigenetic aging><acceleration in epigenetic age><adolescence (12-20)><adolescent trauma><adolescent welfare><adulthood><ages><aging induced epigenetic change><aging-associated epigenetic change><aging-related epigenetic change><biobank><biologic><biorepository><career><child maltreatment><child well being><child wellbeing><childhood adversity><childhood trauma><clinical care><co-morbid><co-morbidity><cohort><comorbidity><cytokine><developmental><developmental psychology><diverse populations><early adversity><early childhood adversity><early life adversity><entire genome><environment effect on gene><epigenetic age clocks><epigenetic aging><epigenetic clock><epigenetic mechanisms in aging><epigenetic modifications in aging><epigenetic molecular clocks><epigenetic regulation of aging><epigenetically><epigenomics><experience><exposure to trauma><faster epigenetic aging><faster rates of epigenetic aging><full genome><gene environment interaction><genetic etiology><genetic mechanism of disease><genetic vulnerability><genetically predisposed><genomic data><genomic data-set><genomic dataset><genomic effort><genomic strategy><heterogeneous population><improved><increased epigenetic age><increased epigenetic aging><increased rates of epigenetic aging><innovate><innovation><innovative><insight><interventional strategy><kids><longitudinal, prospective study><maltreatment><mental><methylation clock><methylome><mistreatment><mortality><multi-modality><multimodality><neuropsychiatric><neuropsychiatry><pediatric><pediatric adversity><pediatric trauma><phenomics><physical abuse><physical conditioning><physical health><physical maltreatment><pleiotropic effect><pleiotropism><pleiotropy><polygenic risk score><population diversity><post-trauma stress disorder><posttrauma stress disorder><professor><psychiatric genetics><psychogenetics><rapid epigenetic aging><sex><sex abuse><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><sexually abused><skills><social role><stressful experience><stressful life event><stressful life experience><systemic inflammation><systemic inflammatory response><training opportunity><translation research><translational genomics><translational investigation><trauma exposure><trauma in children><traumatic neurosis><whole genome><youngster>