About

John Lyons is a Professor of Psychiatry and Behavioral Neuroscience at the Biological Sciences Division of The University of Chicago. His research focuses on child behavioral health, including the evaluation of telehealth services during the COVID-19 pandemic, social determinants of health screening in pediatric care, and psychosocial needs assessment tools for pediatric inflammatory bowel disease. He has contributed to understanding mental health service utilization during emergency department visits among children and youth, as well as decision-making processes and outcomes in child welfare related to out-of-home placements. His work also includes developing and validating assessment tools such as the HEADS-ED for rapid mental health screening in pediatric emergency settings and the ED-SCANS for needs and strengths assessment in sickle cell disease. Dr. Lyons's research aims to improve health service delivery, psychosocial assessment, and health outcomes for children and adolescents.

Research topics

• Computer Science
• Business
• Psychology
• Economic growth
• Social psychology
• Process management
• Economics
• Engineering
• Medicine
• Knowledge management
• Mechanical engineering
• Advertising
• Psychiatry

Selected publications

• Positive developmental cascades: Strength development reduces support needs in children

  JCPP Advances · 2026-01-22

  articleOpen accessSenior author

  Abstract Background Strength development in children across a range of psychiatric diagnoses may reduce needs for mental health, social, and functioning support over time. A strength‐based adjunct to child and adolescent mental health may foster the developmental context most helpful for achieving desired outcomes with positive developmental cascading effects. Methods We longitudinally examined changes across 5 years in the Child and Adolescent Needs and Strengths Assessment in 2‐ to 18‐year‐old children ( N = 30,103) from a public mental health system. Results First, children who began with a greater number of strengths consistently had fewer support needs, not only at entry but also at one, two, three, four, and five years later. Second, initial strengths appeared to have cumulative positive cascades with reduced support needs over time; each additional strength a child possessed at the beginning of service was associated with a progressively faster decrease in their support needs each subsequent year. Furthermore, developing more strengths during the service period also predicted lower support needs one, two, three, four, and five years later. Finally, the impact of developing strengths over time varied depending on the child's age. Developing more strengths was linked to an increasingly rapid reduction in support needs each year for 2‐ to 5‐year‐olds. In contrast, developing more strengths was linked to a progressively slower reduction in support needs each year for 11‐ to 15‐year‐olds. Conclusion We provide empirical support suggesting both the clinical utility of strength‐based behavioral health care and the value of strength development in relation to reduction in support needs as a transdiagnostic clinical dimension. In turn, positive developmental cascading effects during a sensitive period early in development suggest the importance of early intervention. Strength‐based mental health classification and treatment systems can be balanced with a traditional mental health symptom focus to more broadly leverage individuals' abilities for adaptation.

  PublisherOA PDFDOI

• The Impact of Placement Change on Sleep in Child Welfare

  Children · 2026-05-01

  articleOpen accessSenior author

  Background/Objectives: Sleep disturbance is common among youth in the child welfare system, yet the role of placement instability and placement setting in shaping sleep outcomes remains understudied. This study examined the association between placement instability, time spent in different care settings, and sleep disturbance among children in foster care. Methods: We conducted a retrospective cohort study using longitudinal administrative child welfare data from a Midwestern U.S. state, including 20,888 youth aged 5–18 years who entered foster care between 2010 and 2020. Sleep disturbance was assessed using the Child and Adolescent Needs and Strengths (CANS) sleep item. Baseline was defined as the first CANS assessment within one month of entry into care, and follow-up as the assessment closest to discharge or the end of a three-year observation window, whichever occurred first. We estimated association using a time-lagged linear mixed-effects model predicting sleep disturbance after each placement episode, including placement instability: 1 (reference), 2, 3, or ≥4 placement(s), time since placement, time spent in care settings (kinship, foster home, treatment foster home, congregate care, institutional care), and baseline trait factor scores derived from non-sleep CANS items, while controlling for sleep at the time of placement and demographics. Results: At baseline, 2016 children had actionable sleep disturbance (CANS sleep = 2 or 3; 1701 moderate and 315 severe). By the end of follow-up, this increased to 2884 children (2372 moderate and 512 severe). In linear mixed-effects models, placement instability demonstrated a dose–response association with higher subsequent sleep disturbance relative to one placement (2 placements: β = 0.025; 3 placements: β = 0.045; ≥4 placements: β = 0.067; all p ≤ 0.02). Time spent in kinship care was associated with lower sleep disturbance (β = −0.049; p < 0.001), whereas time spent in treatment foster homes was associated with higher sleep disturbance (β = 0.035; p < 0.001). Trauma in the family, medical/developmental needs, and internalizing/sexual issues were positively associated with sleep disturbance. Time and instability interactions showed modest attenuations of instability-associated sleep disturbance over time for higher placement counts. Conclusions: Placement instability is associated with progressively worse sleep disturbance over time among youth in foster care, even after controlling for sleep status at placement and baseline functioning. Sleep disturbance may represent an actionable indicator for the child welfare system, highlighting opportunities for targeted screening and support during placement transitions.

  PublisherDOI

• The role of adverse and positive childhood experiences on mood challenges in child welfare population

  Children and Youth Services Review · 2026-01-15 · 1 citations

  articleSenior author
  PublisherDOI

• Abstract 1627: Switching cell fate from senescence to apoptosis by the combination of a p53 corrector with the MDM2 antagonist ASTX295

  Cancer Research · 2025-04-21

  article

  Abstract Background: ASTX295 is a potent MDM2 antagonist designed to have a shorter half-life (t1/2 4-6 hours in plasma), which leads to an improved safety profile (bone-marrow sparing), making it more amenable to combinations compared to other MDM2 antagonists. The recent success of targeting TP53:Y220C mutant cancers with a p53 corrector molecule holds great promise for treatment of all Y220C TP53 mutant cancers. However, for effective therapy, a high level of p53 signalling will be required to overcome the elevated apoptotic thresholds seen in some cancer cells with co-mutations in pro-survival signalling pathways. We rationalised that this could be achieved by removing the MDM2-driven negative feedback loop that is triggered following Y220C correction. Materials and Methods: Corrected p53 signalling was determined in two TP53:Y220C mutant pancreatic cancer cell lines with additional MAPK mutations: BxPC3 (BRAF:L485-P490del) and T3M-4 (KRAS:Q61H). Two small-molecule TP53:Y220C correctors were tested alone and in combination with ASTX295 using real-time microscopy, western blotting, and qPCR. Markers of p53 signalling (at the protein and mRNA level), senescence (β-galactosidase), apoptosis (Annexin V), and DNA damage (phospho-H2A.X) were measured after treatment with compounds. A mouse xenograft model was established in male CB17 SCID mice inoculated subcutaneously with BxPC3 cells, allowing PK/PD and efficacy evaluation. Results: The combination of ASTX295 and the Y220C corrector led to increased cell death in both BxPC3 and T3M-4 cell lines in vitro, with elevated p53 signalling (p21), apoptosis (PUMA), and DNA damage (phospho-H2A.X) when MDM2 is antagonised. The KRAS mutant line, T3M-4, was less sensitive to the combination, but could be driven to apoptosis at higher concentrations of the corrector. PK/PD evaluation in BxPC3-xenograft-bearing mice demonstrated prolonged p53 signalling following combination treatment up to 16 h post dose, with a subsequent reduction at 24 h consistent with the ASTX295 exposure profile. Conclusions: We have shown that MDM2 antagonism leads to sustained corrected p53 signalling over time, which drives cell death, even in tumor cells harbouring co-mutations conferring higher apoptotic resistance. Indeed, our study provides proof of concept that efficacy could be achieved in multiple tumor types in which the p53 pathway can be targeted therapeutically through combination with ASTX295, which would drive and maintain p53 signalling levels above the apoptotic threshold. Citation Format: George Ward, Judit Espana-Agusti, Keisha Hearn, Mark Wade, Lynsey Fazal, Hugh Walton, Andrea Biondo, John Lyons, Martin Sims, Simone Jueliger, Jessica Brothwood, Andrew Woodhead, Louise Walsh, Tomoko Smyth, Nicola Wilsher, Maria Ahn. Switching cell fate from senescence to apoptosis by the combination of a p53 corrector with the MDM2 antagonist ASTX295 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1627.

  PublisherDOI

• Person-Centered Health Services Research: Policy Implications

  JOURNAL OF MENTAL HEALTH AND CLINICAL PSYCHOLOGY · 2025-08-14

  articleOpen access1st authorCorresponding

  Since the origins of the field of health services research (HSR) in the 1960, investigators have relied on large administrative datasets or national surveys as the primary tools to inform, increase knowledge, and ultimately improve individual patient care processes and outcomes.

  PublisherOA PDFDOI

• Understanding children’s behavioral health outcomes: A story of overcoming trauma and building strengths

  medRxiv · 2024-01-26

  preprintOpen accessSenior author

  Background Among children enrolled in behavioral health treatment, those with multiple trauma experiences (known as Adverse Childhood Experiences, or ACEs) typically see worse outcomes. In this study, we examine whether having or building strengths can help such children become more resilient and experience better outcomes. Objective We examined the relationship between children’s traumatic experiences, strengths, and clinical improvement, testing whether building strengths can help reduce the negative impact of ACEs on children’s response to treatment. Participants and Setting We used data from an evidence-based assessment to understand the clinical and functional needs and strengths of 5,423 children (ages 6-20) receiving treatment between 2019 and 2022 within a large community agency located in California. Methods To classify children by both level and rate of improvement, we relied on machine learning and principal components analysis. To determine the relationships between ACEs, strengths, and improvement, we used a variety of predictive models and descriptive analyses. Results After classifying children as being either “Faster”, “Slower”, or “Minimal” improvers, our analyses revealed that while higher total ACEs increases the likelihood of being a Slower improver, this effect can be mitigated by building strengths. Conclusions These results suggest that children with more ACEs are likely to require a longer duration of treatment before improvement is seen. They also suggest that promoting resilience— specifically focusing on building strengths—may lead to more efficient and effective care, particularly for children with significant trauma histories.

  PublisherOA PDFDOI

• Abstract 3333: Targeting the MDM2-p53 interaction: Time- and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index

  Cancer Research · 2024-03-22 · 3 citations

  article

  Abstract Aim We aimed to design an MDM2-p53 antagonist with a differentiated tolerability profile that could be used to treat patients with wild-type TP53 malignancies. As part of an alliance between Newcastle University, Astex Pharmaceuticals, and Cancer Research Horizons, we discovered ASTX295, a potent inhibitor of the MDM2-p53 interaction that is currently under clinical investigation in patients with solid tumors (NCT03975387). We selected ASTX295 as a compound with a predicted short plasma half-life, which we hypothesised would help to mitigate the dose-limiting neutropenia and thrombocytopenia observed with earlier MDM2-p53 antagonists in clinical studies. To examine this hypothesis in vitro, we determined time- and concentration-dependent responses to ASTX295 treatment in healthy volunteer-derived human bone marrow cells, megakaryocytes, and in a panel of human tumor cell lines. Methods Samples containing bone marrow cells from healthy patients undergoing hip surgery were obtained under the ethical approval of the Newcastle Biobank (REC 12/NE/0395). Following Lymphoprep™ separation, cells were treated ex vivo with ASTX295 and seeded for Granulocyte-macrophage (GM) colony-forming assays in methylcellulose. Megakaryocytes were obtained from in vitro differentiation of CD34+ stem/progenitor cells. Human tumor cell lines (including MDM2-amplified SJSA-1) were treated with ASTX295 in vitro and seeded at low density for colony-forming assays. Exposures of 6, 12, or 24h were examined, and the data plotted to calculate LC50 values. Results The clonogenic survival of tumor cells was time-dependent, with LC50 values (mean ± SEM) in SJSA1 cells being 238 ± 46nM and 75 ± 7nM respectively (n = 3-4), following a 12h or 24h exposure to ASTX295. Time-dependent effects were also evident in five human bone marrow samples but with LC50 values of 1.9, >3, >10, >10, and >10uM being achieved at 12h, and 860 ± 268nM at 24h. Megakaryocytes showed similar time-dependent sensitivities in which daily treatment of 2 or 6h over three days did not induce apoptosis while significant cell death was observed when the treatment time was extended to 16-24h daily. In contrast, short, daily pulse treatment of 2-6h in cell lines (MV4-11, MOLM-13, SJSA-1) over three days was sufficient to induce cell death. Conclusions ASTX295 is a potent antagonist of the MDM2-p53 interaction. Collectively, our in vitro data suggest that a shorter exposure to ASTX295 (up to 12h), may help to spare healthy bone marrow cells whilst killing tumor cells. Hence, intermittent exposure to an MDM2-p53 antagonist could favourably modulate its therapeutic index. The predicted short plasma half-life of ASTX295 should provide flexibility in controlling the duration of exposure in vivo, potentially enabling a more bone-marrow sparing approach to MDM2-p53 antagonism to be utilised. Citation Format: Elaine Willmore, Maria Ahn, Suzanne Kyle, Yan Zhao, Huw Thomas, Kenneth S. Rankin, Luke Bevan, Lynsey Fazal, Keisha Hearn, Nicola Wilsher, Justyna Kucia-Tran, Nicola Ferrari, Nicola Wallis, Neil Thompson, John Lyons, Duncan Miller, Celine Cano, Martin E. Noble, Ian R. Hardcastle, Steven Howard, Gianni Chessari, John Lunec, David R. Newell, Steve R. Wedge. Targeting the MDM2-p53 interaction: Time- and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3333.

  PublisherDOI

• Understanding Children's Behavioral Health Outcomes: A Story of Overcoming Trauma and Building Strengths

  SSRN Electronic Journal · 2024-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Abstract 667: Identification of biomarkers of response to MDM2 inhibition in solid tumours using computational, multi-omics approaches

  Cancer Research · 2024-03-22

  article

  Abstract Background High-throughput drug screening and computational methods to associate genomic features of cell lines to drug sensitivity are valuable tools for predicting biomarkers of sensitivity. In addition, integrating genomic features to expression-based patterns could improve biomarker prediction and patient stratification. Particularly weighted gene co-expression networks represent an effective approach to identify key modules and possible biological mechanisms of sensitivity. Using a combination of cell panel screening and gene co-expression networks, we predicted markers of sensitivity to ASTX295 (MDM2i) in cancer cell lines and confirmed expression-based signatures in publicly available clinical datasets. Method ASTX295 was screened in a panel of 210 p53 wild-type cancer cell lines derived from a range of tumor tissues. ANOVA was used to identify significant associations of genomics features of cell lines to drug response. Transcriptomics profiling of apoptotic and non-apoptotic patient-derived cell lines was performed and significant differentially expressed genes were identified. Further, pathway enrichment and expression-based signatures identified in cell lines were further confirmed in TCGA patient data using weighted gene co-expression network analysis (WGCNA). Expression modules identified by WGCNA were correlated to genomic features and clinical parameters to identify potentially clinically relevant biomarkers. Results Analysis of the cell panel data identified CDKN2A loss as a statistically significant biomarker predictive of sensitivity to ASTX295. As mesothelioma is one of the indications with high prevalence of loss of CDKN2A, the anti-proliferative activity of ASTX295 was further confirmed in an independent panel of p53 wild-type, patient-derived mesothelioma cell lines. Further, pathway and transcriptional regulator analysis identified the Interferon signalling as significantly enriched in apoptotic cell lines and was confirmed in a TCGA mesothelioma patient data set and the module was found to be significantly correlated with a subgroup of P53 wild-type patients with CDKN2A loss. In conclusion, combining cell panel drug screening with co-expression networks helped to identify biomarkers associated with ASTX295 sensitivity, and provided new insights into the underlying mechanism of ASTX295 response. Citation Format: Harpreet Kaur Saini, Maria Ahn, George Ward, Justyna Kucia-Tran, Christina Gewinner, Nicola Ferrari, Jessica Brothwood, Luke Bevan, Matthew Davis, Lynsey Fazal, Martin Sims, Marc O'Reilly, Gianni Chessari, Roberta Ferraldeschi, John Lyons, Nicola Wallis, Neil Thompson. Identification of biomarkers of response to MDM2 inhibition in solid tumours using computational, multi-omics approaches [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 667.

  PublisherDOI

• 42 (PB030): A novel small-molecule CBP/p300 HAT domain inhibitor demonstrates potent in vivo activity and a favorable safety profile in preclinical species

  European Journal of Cancer · 2024-10-01

  article
  PublisherDOI

Frequent coauthors

• Peter de Jonge

  University of Groningen

  266 shared

• Joris P. J. Slaets

  Leyden Academy on Vitality and Ageing

  265 shared

• Thomas Herzog

  Munich University of Applied Sciences

  246 shared

• António Lobo

  Universidad de Zaragoza

  246 shared

• Per Fink

  Aarhus University Hospital

  246 shared

• Nándor Balogh

  243 shared

• Barbara Stein

  Paracelsus Medizinische Privatuniversität

  243 shared

• Graça Cardoso

  Universidade Nova de Lisboa

  243 shared

Labs

• Psychiatry and Behavioral Neuroscience-Research, University of ChicagoPI