California Initiative to Advance Precision Medicine The SYSTEMAATIC Project: Systems-based, Multidisciplinary Assessment of Adversity and Toxic Stress for Individualized Care
Adverse Childhood Experiences demonstration project led by Dr. Sayantani (Tina) Sindher at Stanford University (2022-2025).
Project Summary
This project seeks to:
Background
Currently, the impacts of Adverse Childhood Experiences (ACEs) and toxic stress are detected by symptoms like depression or anxiety or other poor health outcomes, rather than the underlying changes to biomarkers, such as a person's neurologic, endocrine, metabolic, and immune system functions. Current assessment tools and interventions for ACEs and toxic stress are largely siloed and not integrated between mental health, physical health, protective factors, and community voice. The SYSTEMAATIC Project is creating a clinical diagnostic tool for toxic stress by combining multiple disciplines that approach organ systems as a whole, rather than using a symptoms-based approach, which leads to earlier detection of the health impacts of ACEs and toxic stress and, thus, enables more targeted treatments.
Biomarkers (short for biological markers) are indicators that can be measured to determine information about the state of a living thing and include molecules in your blood, proteins, antibodies, genes, etc. Exposure to ACEs and toxic stress can change biomarker levels, especially those related to neurologic, endocrine, metabolic, and immune systems. These disrupted biomarkers might be the earliest signs that an individual is at risk of developing toxic stress physiology and other health conditions. Diagnostic biomarkers can be used to diagnose health conditions and diseases and provide indications for treatment plans, based on which biomarkers are deficient or above normal levels in your body.
Project Goals
The goal of the SYSTEMAATIC Project is to use precision medicine approaches to:
- Develop a multidisciplinary Toxic Stress Assessment Profile that identifies disruptions in the neurological, endocrine, metabolic, and immune pathways under stress in adults.
- Pilot the feasibility, adaptability, and validity of the Toxic Stress Assessment Profile and the impact of interventions for adults within partner clinics and organizations; taking into consideration community-specific barriers to develop feasible interventions.
Through their approach, the Stanford team aims to provide a transformative impact on ACE-Associated Health Conditions through identification of dysregulated biomarkers across neurological, endocrine, immune, and metabolic systems. This biomarker approach would then allow providers to identify patients who might otherwise be missed by the symptomatic approach. Additionally, through the development of a system for multidisciplinary, integrated care that accounts for protective factors and community voices, the Stanford team envisions that their approach will lead to improved clinical practices to diagnose toxic stress, guide recommendations for integrated precision medicine treatment, and ultimately assess treatment efficacy.
Team Leaders
Tina Sindher, MD is an Allergist and Immunologist whose main research focuses on advancing the current understanding of atopic disorders, the interplay between different allergic conditions, and how this knowledge can be applied to prevention strategies, better diagnostics, and the development of novel therapeutics. She is a co-founder of the National Committee on Asthma and Toxic Stress (NCATS) in collaboration with the Center for Youth Wellness (CYW). With the help of a diverse group of experts, the committee focuses on highlighting the connection between adverse childhood experiences (ACEs), associated ethnic/racial disparities, and the connection with asthma. The committee aims to develop integrated multidisciplinary management guidelines for asthma in the setting of toxic stress.
Dr. Sindher obtained her MD at SUNY Downstate College of Medicine, pediatric residency at the Childrens Hospital at Montefiore, and allergy fellowship at Childrens Hospital of Philadelphia.
Dr. Rachel Gilgoff is an Adjunct Clinical Associate Professor of Pediatrics, Allergy, and Clinical Immunology at Stanford University School of Medicine and a Clinical and Science Senior Advisor for the Aurrera Health Group ACEs Aware Initiative and the Center for Youth Wellness, a program of Safe and Sound. Dr. Gilgoff brings a vast array of experiences and expertise, including her roles as a child abuse pediatrician at the Center for Child Protection at the UCSF Benioff Children’s Hospital & Research Center in Oakland, a co-investigator with the Bay Area Research Consortium, and a Medical Director of the Clinical Innovations and Research Team within the Center for Youth Wellness. Dr. Gilgoff received her MD from USC and completed her residency in Pediatrics at Children’s Hospital and Research Center Oakland. She has completed several fellowships: a joint Child Abuse Pediatrics fellowship at UC Davis and Children’s Hospital and UCSF Benioff Children’s Hospital Oakland, a Pediatric Integrative Medicine fellowship at Stanford, Integrative Medicine at the Andrew Weil Center for Integrative Medicine, and Integrative Psychiatry fellowship at the Integrative Psychiatry Institute.
Lisa Chamberlain, MD, MPH, Professor of Pediatrics, Associate Chair of Policy and Community and the Arline and Pete Harman Faculty Scholar at Stanford Children's Hospital. Dr. Chamberlain has focused her career on the elimination of child health disparities. She is committed to do this in two ways: 1) transforming the way pediatricians practice by developing and disseminating models of community engaged pediatrics by combining principles from both medicine and public health, and 2) conducting health services research to inform policy. She founded and co-directs the Stanford Pediatric Advocacy Program to train leaders in Community Pediatrics and Advocacy. She co-founded the California Community Pediatric Collaborative, uniting 14 training programs to advance education addressing pediatric health disparities.
Dr. Chanberlain obtained her MD at University of Arizona College of Medicine completed her pediatric training at Stanford, a General Academic Fellowship at UCSF/Stanford, and her MPH at UC Berkeley.
Hadi Hosseini, PhD is a computational/cognitive neuroscientist investigating large-scale structural and functional brain networks in various neuropsychiatric disorders using multimodal neuroimaging, graph theoretical and multivariate pattern analyses techniques. He is also developing novel NIRS-based neurofeedback interventions for enhancing executive functions.
Dr. Hosseini obtained his PhD in Engineering and his postdoctoral work on Neuro-ergonomics at Tohoku University, and postdoctoral work in Psychiatry at Stanford University.
Safwan Jaradeh, MD obtained his MD at the University of Damascus, residency at La Pitie-salpetriere and Bicetre Hospitals, Universite de Pierre et Marie Curie and University of Cincinnati Medical Center; and two of his several fellowships include Mayo Clinic and Departments of Neurology and Physical Medicine and Rehabilitation at the University of Michigan.
Dr. Jaradeh's clinical interests include autonomic disorders, small fiber neuropathies, and the development of effective methods for testing and treating these disorders. Prior work has focused on 1) small fiber, painful, and autonomic neuropathies 2) syncope and syndromes of orthostatic intolerance, including postural orthostatic tachycardia (POTS), 3) gastrointestinal motility dysfunction, 4) cyclic vomiting, 5) neurology of gastroesophageal reflux, 6) non-allergic rhinitis syndromes, and 7) the relationship between the autonomic nervous system and normal or abnormal sleep. Additional areas of interest include the neurology of phonation and swallowing disorders, autoimmune neuromuscular disorders, hereditary neuropathies, and peripheral nerve injury and repair.
Dr. Jaradeh is board certified in Neurology and in Clinical Neurophysiology by the American Board of Psychiatry and Neurology. He is also board certified in Electrodiagnostic Medicine by the American Association of Neuromuscular & Electrodiagnostic Medicine, and board certified in Autonomic Disorders by the UCNS Board of the American Autonomic Society. Before joining Stanford Hospital and Clinics, Dr. Jaradeh served as Chair and Professor at Medical College of Wisconsin from 2000 to 2011.
Ann Ming Yeh, MD is a Clinical Associate Professor at Stanford University in Pediatric Gastroenterology and practices at Lucile Packard Children’s Hospital and Stanford Children’s Health. Dr. Yeh’s research interests include diet therapies for inflammatory bowel disease, nutrition, small intestinal bacterial overgrowth, and integrative medicine for pediatric gastroenterology. She is currently the program director for the nation’s premier fellowship for Pediatric Integrative Medicine at Stanford.
Dr. Yeh obtained her MD at Albert Einstein College of Medicine, residency at Stanford Health Care at Lucile Packard Children's Hospital, and fellowship in University of Arizona Center for Integrative Medicine and in pediatric gastroenterology at Stanford University.
Ryan Padrez, MD is a pediatrician and Assistant Clinical Professor of Pediatrics at Stanford University's Division of General Pediatrics. His primary clinical practice is at Gardner Packard Children's Health Center. In addition to his work at Stanford, Ryan also serves as the Medical Director for The Primary School, a new integrated health and education model that serves low-income children and families in East Palo Alto, CA. His work and leadership focuses on the intersection and reform of primary pediatric care and childhood education. He works to integrate systems and promote models that ensure high quality care is accessible to all children.
Dr. Padrez obtained a BA in human biology at Stanford, earned his MD at University of California, San Francisco (UCSF). He completed his pediatric residency at UCSF and participated in UCSF's Pediatric Leadership for the Underserved (PLUS) program. He went on to complete a chief resident year at The San Francisco General Hospital and Trauma Center.
Michael Snyder is the Stanford Ascherman Professor and Chair of Genetics, and the Director of the Center of Genomics and Personalized Medicine. He received his PhD training at the California Institute of Technology and carried out postdoctoral training at Stanford University School of Medicine. Dr. Snyder has pioneered the use of “big data” and multiomics to advance scientific discovery and transform healthcare. His laboratory has invented many technologies that are widely used in medicine and research, including methods for characterizing genomes and their products (e.g. RNA-Seq, NGS paired end sequencing, ChIP-Chip and later ChIP-Seq, protein arrays, machine learning for disease gene discovery). His application of omics and wearables technologies to perform longitudinal profiling of people when they are healthy and ill is transforming medicine and healthcare. Indeed, his laboratory’s recent work to use smartwatches and wearables to detect illness, including infectious disease such as COVID-19 prior to symptom onset, is being used by many thousands of people. He has helped co-lead many large-scale projects including ENCODE, HMP, HuBMAP and HTAN. He has cofounded 16 biotechnology companies, including Personalis, Qbio, January AI, Filtricine and RTHM.
Partners, Collaborators, and Supporters
- Aurrera Health Group
- Tanya Schwartz MPP, MSW
- California Health Collaborative
- Center for Youth Wellness/Safe and Sound
- Bre Gentile, PhD
- Central Valley Community Foundation
- Artie Padilla
- Fresno Community Health Improvement Partnership (FCHIP)
- Sue Kincaid
- Federally Qualified Health Center (FQHC) clinics of San Mateo Medical Center
- Elizabeth Grady, MD
- Sean N. Parker Center for Allergy & Asthma
- South San Francisco Clinic
- Stanford Precision Health for Ethnic and Racial Equity
- Ryan Padrez, MD