Current Projects
Epigenetic determinants influencing development and evolution of chronic post-surgical pain in children undergoing musculoskeletal surgery
Spine fusion and pectus repair are among the most painful musculoskeletal surgeries adolescents undergo, with a high incidence of CPSP. Understanding CPSP risk is important for development of effective preventive and therapeutic strategies. Although genetic, psychosocial and environmental factors explain some of the variance in CPSP risk, there remain critical gaps in CPSP risk prediction and understanding of longitudinal gene-environmental influences on long-term pain responses after surgery. This lead to the global hypothesis that epigenetic processes will influence the development and evolution of CPSP. DNA methylation (DNAm) is a key epigenetic mechanism known to influence transcription and transition of acute to chronic pain.
Project Goals: To determine blood DNAm biomarkers for CPSP and evaluate temporal origins of CPSP-associated epigenetic variation in relation to pain-opioid exposures and inflammatory responses.
Funding: NIH2019R01AR (NIH/NIAMS) - 8/1/2019-7/31/2024
Collaborators: Clinical pharmacology (Dr.Vinks), Epigenetics (Artem Barski/Hong Ji), QST (Chris King), Bioinformatics (Matthew Weirauch, Jarek Meller), Surgeons (Garcia, Sturm), Biostats (Lili Ding)
Collaborators on Multisite Study Aim: Duke University (Einhorn), CHOP (Arjunan Ganesh), Stanford (RJ Ramamurthy), Hopkins (Monitto)
> View more information on clinicaltrials.gov.
Relationship between CPSP, inflammation and regulation of inflammatory gene expression
In this project, we are recruiting patients undergoing spine and pectus surgeries. Differences in blood cell composition, gene expression and DNA accessibility profiles will be examined in immune cell subsets from CPSP patients and pain-free controls.
Project Goal: To examine the relationship between CPSP, inflammation and regulation of inflammatory gene expression.
Funding: 2018 Charlotte R. Schmidlapp Women Scholars Program Award
Collaborators: Immunogenetics (Artem Barski), Biostats (Lili Ding), Epigenetics stats support (Xue Zhang)
> View more information on clinicaltrials.gov.
Morphine Pharmacogenomics to Predict Risk of Respiratory Depression in Children
The goal of this project is to evaluate genetic (OPRM1, FAAH and ABCB1) and non-genetic determinants of morphine induced respiratory depression in adolescents undergoing spine fusion.
Role: Principal Investigator
Project Goal: The goal of this project is to evaluate genetic (OPRM1, FAAH and ABCB1) and non-genetic determinants of morphine induced respiratory depression in adolescents undergoing spine fusion.
Funding: 1K23-HD082782-01A1 (NIH/NICHD) 09/01/2014 – 7/31/2019
Mentors: Primary (James Heubi, Wolfgang Sadee); Secondary (Sander Vinks, Lisa Martin, Senthilkumar Sadhasivam)
Collaborator: Jarek Meller
> View more information on clinicaltrials.gov.
Pharmacogenetics; psychosocial, genetic and epigenetic predictors of acute and chronic post-surgical pain
Our prospective studies of postoperative and chronic postsurgical pain in adolescents undergoing spine surgery and pectus surgery seek to identify genetic, psychologic and perioperative predictors for pain. Parent-child psychological factors including child anxiety sensitivity index and perioperative pain experience were found to significantly influence development of pain persistence. We also conduct PK/PD studies to identify factors affecting the pharmacometrics of opioids in these surgical populations.
Project Goal: The goal of this project is to identify genetic, psychologic and perioperative predictors for pain in adolescents undergoing spine, pectus and other invasive surgeries.
Collaborators: Clinical pharmacology (Sander Vinks), Genetics (Lisa Martin/Valentina Pilipenko), BMCP (Kashikar-Zuck), Epigenetics (Hong Ji, Xue Zhang), Bioinformatics (Anil Jegga/Matthew Weirauch)
> View more information on clinicaltrials.gov. (Comprehensive Study of Post-surgical Pain After Pectus or Spine Surgery)
> View more information on clinicaltrials.gov. (Patient Controlled Analgesia Pharmacogenetic Study)
Mixed methods study to understand pain disparities by race and ethnicity
Funded by: CCTST Community health grant
Collaborators: Monica Mitchell
Students: Julia Kumar, Dylan Atkinson
Other Projects:
EEG-biofeedback based brief preoperative mindfulness to improve pain coping in children
Project goal: We are conducting feasibility studies for a brief mindfulness intervention after preoperative training in biofeedback and the use of MUSE headbands for mindfulness in children before invasive surgeries (like pectus surgery). This is a randomized controlled trial and will evaluate feasibility and outcomes including pain coping and perioperative pain trajectories.
Funding: Anesthesia Innovation pilot funding from Anesthesia department, Cincinnati Children's.
Collaborators: QST (King), Integrative medicine (Baker/Wood), surgery (Garcia)
> View more information on clinicaltrials.gov.
Neurochemical imaging to identify correlations of GABA/Glu metabolites in pain specific brain areas with pain sensitivity, post-surgical pain outcomes and epigenetic markers
Project goals: Characterize the brain metabolite status of the ACC and insula in presurgical adolescents and to understand the relationship between metabolite levels and CPSP. We will also examine whether neurochemical tone in these regions is related to resting state functional connectivity with other brain regions.
Funding: Mind Brain Behavior Funding (2020)
Cincinnati Children's Collaborators: Clinical pharmacology (Dr. Vinks), Genetics (Lisa Martin), Epigenetics (Artem Barski/Hong Ji), QST (Chris King), Bioinformatics (Matthew Weirauch, Anil Jegga, Jarek Meller), Surgeons (Garcia, Sturm), Biostats (Lili Ding), Imaging (Coghill, Cecil), BMCP (Kashikar-Zuck)
Collaborators on Multisite Study: Duke University (Einhorn), CHOP (Arjunan Ganesh), Stanford (RJ Ramamurthy), Hopkins (Monitto)
Collaborating Cores: CAGE, DNA sequencing
