Faculty Bibliography

Dpep is a cell-penetrating peptide that targets transcription factors ATF5, CEBPB and CEBPD to selectively suppress growth and survival of diverse tumor cell types in vitro and in vivo. Due to these actions and its apparent safety, the peptide has potential as a cancer therapeutic. How Dpep might be combined with other anti-cancer agents to achieve synergistic efficacy and to overcome possible peptide resistance has not been assessed in depth. Based on prior work indicating that Dpep promotes apoptotic cancer cell death and up-regulates multiple pro-apoptotic and tumor suppressor genes, we studied combinations of Dpep with ABT-263, a pro-apoptotic BCL2 family inhibitor, and decitabine, a hypomethylating drug. Combining Dpep with each agent alone or together synergistically suppressed the growth of a range of solid and liquid tumor cell types. Moreover, the combinations synergistically inhibited the growth of cells lines that were selected either in vivo or in vitro for Dpep resistance. Finally, we tested the combination of Dpep with ABT-263 in a mouse melanoma xenograft model. The combination more effectively inhibited tumor growth than either agent alone and, in contrast to vehicle or ABT-263, produced a 40% durable survival rate. Taken together, these observations highlight potential drug partners for the therapeutic development of Dpep.

School-based health centers (SBHCs) play a key role in connecting youth to health services, including primary care. Despite some literature exploring their mental health services, little is known about the role SBHCs play in screening for and treating eating disorders. In this study, we surveyed 56 SBHC providers, assessing their familiarity with providing care and screening for mental health concerns, including eating disorders. We also qualitatively explored areas to improve efforts around mental health care and screening. Results suggest that while the majority of participants indicated that they were familiar with mental health disorders, they were less familiar with eating disorders. Furthermore, despite rating screenings for eating disorders of great importance, the frequency of such screenings was comparably lower. Qualitative findings highlight two emerging themes focused on addressing gaps in mental health care: (a) training, continuing education, and addressing misconceptions around eating disorders; and (b) SBHC staffing and resource constraints.

In the face of a growing mismatch between candidates awaiting transplantation and the supply of conventional donor organs, attention has shifted toward novel methods to increase the donor pool, including the use of donation after circulatory death (DCD) and the refinement of procurement techniques that safeguard graft quality. Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a new strategy, leveraging extracorporeal support to curtail warm-ischemic injury while permitting in situ functional assessment. This review covers the rationale behind the use of TA-NRP, while outlining its use during procurement and the current body of evidence gathered on it implementation in lung transplantation specifically.

COP30 in Belém highlighted the urgent intersection of climate change, air pollution, and cardiovascular health. Climate hazards including heatwaves, floods, wildfires, and deteriorating air quality disproportionately affect vulnerable populations, exacerbating cardiovascular disease and straining fragile health systems. Air pollution, a major contributor to global CVD mortality, shares common sources with climate change, yet both act through distinct health pathways. Low- and middle-income countries face the greatest burden, reflecting inequities in social determinants, energy use, and urban infrastructure. The World Heart Federation emphasizes that climate action is cardiovascular action: reducing emissions, improving air quality, and building climate-resilient health systems are among the most effective preventive cardiology interventions. The Belém Health Action Plan provides a framework for integrating CVD into national climate strategies, strengthening health system preparedness, and fostering community resilience. Political leadership is critical to translate commitments into tangible health gains, as exemplified by successful urban interventions. Protecting hearts requires protecting the planet; coordinated climate-health action offers a pathway to healthier populations and sustainable societies.

Recent advances have furthered our understanding of the role of the tumor draining lymph node (TDLN) in the immune response to thoracic malignancies. This review synthesizes the rapidly expanding evidence that tumor draining lymph nodes (TDLNs) are not passive conduits of metastasis but dynamic immunologic organs that shape anti-tumor immunity in non-small cell lung cancer (NSCLC). Across cytokine, cellular, genomic, transcriptomic, and metabolic domains, the TDLN microenvironment becomes progressively remodeled towards immune suppression. These changes influence tumor growth and early metastasis, and may dictate responsiveness to various treatment modalities. The TDLN is also a practical and clinically relevant site for biomarker discovery and therapeutic innovation as a target of drug delivery and immunomodulation.

Inflammatory myocardial and pericardial syndromes (IMPS), including myocarditis, pericarditis, and overlapping myopericardial syndromes, constitute a heterogeneous group of immune-mediated cardiac disorders with clinical trajectories ranging from complete recovery to progressive heart failure and sudden death. This state-of-the-art review synthesizes current insights into immunopathogenesis, emphasizing the interplay among genetic susceptibility, environmental factors, and systemic inflammatory drivers, including rheumatological diseases. A pragmatic diagnostic framework is presented; it integrates targeted serological evaluation, genetic testing, multimodality imaging, and selective endomyocardial biopsy to enable precise etiologic classification. Therapeutic strategies are examined across the spectrum of disease severity, including guideline-directed medical therapy for heart failure, immunosuppression for autoimmune and fulminant phenotypes, and cytokine-directed biologics for recurrent pericarditis. Prognostic determinants, indications for advanced heart failure therapies, and emerging directions in precision immunology, molecular profiling, and AI-enabled risk stratification are discussed to guide future clinical and translational advances.

Post-traumatic stress disorder (PTSD) is a maladaptive and debilitating psychiatric disorder that develops after exposure to a severe traumatic event. PTSD is characterized by intrusive re-experiencing of traumatic memories, avoidance of trauma reminders, negative alterations in cognition and mood, and changes in arousal and reactivity. PTSD is prevalent, with tens of millions of patients in the USA alone affected. The lifetime prevalence worldwide is estimated to be about 4-6%, but it can occur in up to 25-30% of people who experience severe psychological trauma, such as combat veterans, refugees and assault victims. PTSD is highly comorbid with major depressive disorder, anxiety disorders and substance use disorders, and it is a leading cause of suicide. PTSD also increases the risk of multiple medical problems including cardiovascular and metabolic disorders. We review the epidemiology and diagnostic aspects of PTSD in adults, the mechanistic and neurobiological understanding of the syndrome - from neural circuitry to genetic mechanisms - as well as medication, psychotherapy and other trauma-informed treatment approaches to PTSD and trauma-related syndromes.

PURPOSE/OBJECTIVE:Prospective, multi-institutional surgical data collection in pediatric neuro-oncology remains limited despite substantial variation in operative and perioperative management across institutions. To address this, we are developing the NeuroPoint Alliance (NPA) Quality Outcomes Database (QOD) Pediatric Tumor Surgery Registry. Here, we used a modified Delphi process to define a core outcome set for the registry. METHODS:A modified Delphi study was conducted among pediatric neurosurgeons serving as site principal investigators for the proposed registry. Candidate data elements were rated on a 9-point Likert scale. Consensus for inclusion was predefined as ≥70% of respondents rating an item 7-9 and ≤15% rating it 1-3; consensus for exclusion was defined as the reverse. Items not reaching consensus in Round 1, along with new items derived from free-text responses, were re-evaluated in Round 2. Near-consensus items after Round 2 underwent discussion and re-rating in a final virtual round. RESULTS:In Round 1, 48 of 83 candidate items (57.8%) reached consensus for inclusion, while 35 advanced to Round 2. Fourteen additional candidate items were generated from free-text suggestions, resulting in 49 items evaluated in Round 2; 13 reached consensus for inclusion. Seventeen items were classified as near-consensus and advanced to the final round, in which 4 reached consensus for inclusion and 1 for exclusion. Across all three rounds, 66 items achieved consensus. CONCLUSIONS:This modified Delphi study established a consensus-based core outcome set for the NPA QOD Pediatric Tumor Surgery Registry, providing a practical foundation for standardized, prospective, multicenter pediatric neurosurgical oncology data collection.

Linking T cell phenotypes with antigen specificity and functional avidity is critical for understanding in vivo immune responses in infection and cancer. Here, we develop PRECISE-seq, a method that integrates multi-omics T cell analysis with contact-dependent proximity labeling for rapid screening of disease-relevant T cell repertoires, and for linking the relative TCR avidity with T cell phenotypes at single-cell resolution. PRECISE-seq accurately retrieves CMV-specific clonotypes from human peripheral blood and quantitatively measures functional avidity in physiological contexts. We find that high-potency CMV-specific T cells preferentially acquire an exhausted phenotype. In tumors, polyclonal tumor-reactive CD8+ T cells predominantly differentiate into a protumor Ly49+ regulatory state (TLy49), characterized by inhibitory killer cell lectin-like receptor expression and originating from effector memory T cells along a trajectory distinct from exhaustion. Notably, PD-1 blockade reduces TLy49 formation and promotes effector revival, which correlates with responsiveness to immunotherapy. Together, PRECISE-seq enables high-resolution mapping of TCR potency and T cell phenotype, revealing a regulatory axis shaping T cell fate in tumors.

IMPORTANCE/UNASSIGNED:The physician-scientist workforce has been in decline for decades, and the shortage of physician-scientists from racial and ethnic groups that are underrepresented in medicine (URiM) is particularly acute. Medical school is a key developmental period during which research career intentions (RCI) may change, yet little is known about RCI evolution during this period. OBJECTIVE/UNASSIGNED:To evaluate factors associated with RCI among first-year medical students, overall and by URiM status. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This is a cross-sectional analysis of baseline data from the ongoing Longitudinal Evaluation of Research Career Intentions Among Medical Students Study. Participants were first-year medical students enrolled during the 2024 to 2025 academic year at US medical schools accredited by the Liaison Committee on Medical Education. MD-PhD students were excluded. EXPOSURES/UNASSIGNED:The baseline survey collected information on sociodemographic factors, pre-medical school and first-year research experiences (eg, research education, research participation, mentorship, and authorship), medical school learning environment, and psychosocial characteristics. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was RCI in year 1 of medical school, defined as intending to be significantly or exclusively involved in research during one's medical career. Characteristics associated with RCI were evaluated using stability selection. RESULTS/UNASSIGNED:Among 1136 first-year medical student respondents (mean [SD] age, 24.7 [2.7] years; 790 female [69.5%]) at 134 US medical schools, 26.9% (306 students) reported RCI, with a slightly higher prevalence among URiM students than non-URiM students (246 students [28.2%] vs 60 students [23.9%]; standardized mean difference, 0.097). Prematriculation factors associated with RCI among all students included research participation (odds ratio [OR], 1.51; 95% CI, 1.13-2.00), conference presentation (OR, 1.56; 95% CI, 1.16-2.09), and manuscript authorship (OR, 1.38; 95% CI, 1.03-1.86). Postmatriculation factors included research participation (OR, 1.74; 95% CI, 1.31-2.30) and having a physician-scientist role model (OR, 1.72; 95% CI, 1.31-2.30). Factors uniquely associated with RCI among URiM students included prematriculation research experiences (OR, 1.51; 95% CI, 1.14-2.01) and presentation of research (OR, 1.57; 95% CI, 1.17-2.11) and postmatriculation manuscript authorship (OR, 1.84; 95% CI, 1.04-3.25). Among non-URiM students, only postmatriculation factors were uniquely associated with RCI, including having a research mentor (OR, 1.76; 95% CI, 1.34-2.31) and receiving education about physician-scientist work-life balance (OR, 1.63; 95% CI, 1.24-2.15). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cross-sectional analysis of baseline data from an ongoing cohort study found that RCI was prevalent among first-year medical students and was associated with characteristics and experiences prior to matriculation and during year 1. Some factors associated with RCI differed between URiM and non-URiM medical students, suggesting distinct pipelines to research career development. These findings highlight opportunities to support physician-scientist training through tailored education, exposure, and mentorship.