Faculty Bibliography
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school:SOM
Department/Unit:Cell Biology
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14183
The International Guideline for the Definition, Classification, Diagnosis and Management of Urticaria
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
PMID: 41649409
ISSN: 1398-9995
CID: 6000592
Establishing dermatopathology encyclopedia DermpathNet with Artificial Intelligence-Based Workflow
Accessing high-quality, open-access dermatopathology image datasets for learning and cross-referencing is a common challenge for clinicians and trainees. To establish a comprehensive open-access dermatopathology dataset for educational, cross-referencing, and machine-learning purposes, we employed a hybrid workflow to curate and categorize images from the PubMed Central (PMC) repository. We used specific keywords to extract relevant images, and classified them using a novel hybrid method that combined deep learning-based image modality classification with figure caption analyses. Validation on 651 manually annotated images demonstrated the robustness of our workflow, with an F-score of 89.6% for the deep learning approach, 61.0% for the keyword-based retrieval method, and 90.4% for the hybrid approach. We retrieved over 7,772 images across 166 diagnoses and released this fully annotated dataset, reviewed by board-certified dermatopathologists. Using our dataset as a challenging task, we found the current image analysis algorithm from OpenAI inadequate for analyzing dermatopathology images. In conclusion, we have developed a large, peer-reviewed, open-access dermatopathology image dataset, DermpathNet, which features a semi-automated curation workflow.
PMID: 41651886
ISSN: 2052-4463
CID: 6000722
A targetable developmental program co-regulates angiogenesis and immune evasion in melanoma
Ultraviolet (UV)-induced DNA mutations generate genetic drivers of cutaneous melanoma and numerous neoantigens that can trigger anti-tumor immunity. Melanoma cells must therefore rapidly evade immune detection by modulating cell-autonomous epigenetic mechanisms and tumor-microenvironment interactions. Although angiogenesis typically facilitates immune infiltration, solid tumors increase vascularization while limiting immune cell entry. By comparing transcription factor (TF) expression across early-stage melanoma, naevi, and other cancers, we found that the homeodomain TF HOXD13 drives a melanoblast-like program upregulated in melanoma and strongly correlated with angiogenesis and immune cell exclusion. Using transcriptomics, 3D chromatin profiling, and in vivo models, we show that HOXD13 promotes tumor growth by enhancing angiogenesis and suppressing T-cell infiltration. HOXD13 orchestrates 3D enhancer-promoter contacts activating VEGFA, SEMA3A, and CD73, which remodel vasculature and elevate immunosuppressive adenosine. Consistently, HOXD13-induced tumor growth is reversed by combined VEGFR and adenosine receptor (AdR) inhibition, revealing a dual pro-angiogenic and immunosuppressive HOXD13 axis with therapeutic relevance.
PMID: 41631877
ISSN: 2159-8290
CID: 5999692
Synovial Fluid Biomarkers in the Contralateral Knee Predict Patient-Reported Outcomes After Injury at Long-term Follow-up
BACKGROUND:Inflammatory biomarkers in an injured knee have been shown to predict outcomes, yet the role of the subsequent systemic inflammatory response to injury remains poorly understood. PURPOSE/OBJECTIVE:To investigate whether synovial fluid (SF) biomarkers from the contralateral uninjured knee could predict long-term patient-reported outcomes (PROs) for the operative knee in patients undergoing arthroscopic knee surgery. STUDY DESIGN/METHODS:Case series; Level of evidence, 4. METHODS:This retrospective analysis included patients undergoing knee SF aspiration before arthroscopy with ≥8 years of follow-up. SF was aspirated from both the injured and healthy contralateral knees, and concentrations of 10 pro- and anti-inflammatory biomarkers were quantified. Patients completed visual analog scale (VAS) for pain score, Lysholm, Tegner, and Knee injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) surveys preoperatively and at the final follow-up. Stepwise linear regression was performed to identify the most significant predictor(s) of PRO scores utilizing log-normalized contralateral biomarker concentration, age, body mass index, injury type, and Outerbridge grade as covariates. Concentrations from the contralateral knee were also compared with the injured knee to assess for correlations. RESULTS:= .006) score at the final follow-up. Contralateral concentrations of monocyte chemotactic protein 1, macrophage inflammatory protein 1β, vascular endothelial growth factor, and TIMP-1 were correlated with levels in the operative knee but at significantly lower concentrations. CONCLUSION/CONCLUSIONS:SF biomarker levels in the contralateral uninjured knee at the time of arthroscopy were predictive of long-term outcomes for the operative knee. Increased levels of pro-inflammatory biomarkers were predictive of worse outcomes, while anti-inflammatory cytokines predicted improved scores. These results suggest that unilateral knee injury can result in a broader systemic inflammatory response that influences long-term outcomes in patients.
PMID: 41626727
ISSN: 1552-3365
CID: 5999512
Journal of the European Academy of Dermatology & Venereology. 2026:40(2):210-223.DOI: 10.1111/jdv.20833
Statement from the frontal fibrosing alopecia international expert alliance: SOFFIA 2024
BACKGROUND:As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA. OBJECTIVE:To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA. METHODS:Sixty-nine hair experts from six continents were invited to participate in a three-round Delphi process. The final stage was held as a virtual meeting facilitated via Zoom. The consensus threshold was set at ≥66%. RESULTS:Of 365 questions, expert consensus was achieved in 204 (56%) questions following completion of the three rounds. Three additional questions were included at the final meeting. The category with the strongest consensus agreement was disease monitoring (9; 100%). Questions pertaining to physical therapies achieved the least category consensus (15; 40%), followed by systemic therapy (45; 43%). LIMITATIONS/CONCLUSIONS:The study lacked sufficient representation from Africa and South America. CONCLUSION/CONCLUSIONS:SOFFIA highlights areas of agreement and disagreement among experts. Robust research is warranted to provide evidence-based treatment recommendations.
PMID: 40698981
ISSN: 1468-3083
CID: 5901552
LetA defines a structurally distinct transporter family
Membrane transport proteins translocate diverse cargos, ranging from small sugars to entire proteins, across cellular membranes1-3. A few structurally distinct protein families have been described that account for most of the known membrane transport processes4-6. However, many membrane proteins with predicted transporter functions remain uncharacterized. Here we determined the structure of Escherichia coli LetAB, a phospholipid transporter involved in outer membrane integrity, and found that LetA adopts a distinct architecture that is structurally and evolutionarily unrelated to known transporter families. LetA localizes to the inner membrane, where it is poised to load lipids into its binding partner, LetB, a mammalian cell entry (MCE) protein that forms an approximately 225 Å long tunnel for lipid transport across the cell envelope. Unexpectedly, the LetA transmembrane domains adopt a fold that is evolutionarily related to the eukaryotic tetraspanin family of membrane proteins, including transmembrane AMPA receptor regulatory proteins (TARPs) and claudins. Through a combination of deep mutational scanning, molecular dynamics simulations, AlphaFold-predicted alternative states and functional studies, we present a model for how the LetA-like family of membrane transporters facilitates the transport of lipids across the bacterial cell envelope.
PMID: 41565823
ISSN: 1476-4687
CID: 5988502
A Road Map to Understanding Cardiovascular Disease in Diabetes: From the AHA Strategically Focused Research Network in Cardiometabolic Health and Type 2 Diabetes
Despite major advances in medical therapies and prevention strategies, the risk of cardiovascular complications in patients with both type I and type II diabetes remains substantially elevated. In 2019, the American Heart Association sought applications for a Strategically Focused Research Network on Cardiometabolic Health and Type 2 Diabetes. In 2020, 4 centers were named, including Brigham and Women's Hospital, Johns Hopkins University, New York University, and the University of Iowa. These centers performed basic, translational, and clinical studies to provide insights to explain the over 2-fold risk of cardiovascular complications in diabetes. Clinical studies and studies in cells and animals aimed to uncover new mechanisms responsible for disease development. Studies using human populations sought to uncover new biomarkers to prognosticate risk. In this review, we discuss several key issues and current and developing methods to understand why diabetes drives atherosclerotic cardiovascular disease and heart failure. Both human data and experimental models are considered. We integrate a review of these topics with work from the Strategically Focused Research Network and conclude with suggestions for identifying novel risk factors and future experimental research.
PMID: 41538415
ISSN: 1524-4571
CID: 5986562
Advances in Adipose Tissue Biology
Adipose tissue has emerged as a central regulator of human physiology, with its dysfunction driving the global rise in obesity-associated diseases, such as type 2 diabetes, cardiovascular and liver diseases, and several cancers. Once thought to be inert, adipocytes are now recognized as dynamic, responsive cells essential for energy homeostasis and interorgan communication, including the brain. Distinct adipose depots support specialized functions across development, sex, and aging. Technologies like single-cell RNA sequencing are unraveling depot-specific mechanisms, with the potential of identifying new therapeutic targets. This review highlights major scientific advancements leading to our current appreciation of the pivotal role of adipose tissue in health and disease. Many key discoveries in this field have been catalyzed by National Institutes of Health funding, particularly through the National Institute of Diabetes, Digestive and Kidney Diseases, now celebrating its 75th anniversary.
PMID: 41071598
ISSN: 1945-7189
CID: 5952392
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2026:123(2).DOI: 10.1073/pnas.2500723123
Elevator mechanism dynamics in a sodium-coupled dicarboxylate transporter
VcINDY, the sodium-dependent dicarboxylate transporter from
PMID: 41490488
ISSN: 1091-6490
CID: 5980652
Population analysis and immunologic landscape of melanoma in people living with HIV
PURPOSE/OBJECTIVE:To dissect the clinical and immunological features of people living with HIV (PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer. EXPERIMENTAL DESIGN/METHODS:We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n=11), with downstream validation using multiplex immunofluorescence (n=15 PLWH, n=14 PLw/oH). RESULTS:PLWH were diagnosed at a younger age, had greater representation of Hispanic and Black individuals, and showed reduced survival. They also had a markedly increased risk of brain metastases. PLWH experienced significant delays in initiating immune checkpoint inhibitor (ICI) therapy and had worse post-ICI survival, even after balancing covariates. Spatial transcriptomics revealed a more immunosuppressive tumor microenvironment in PLWH, with increased transcription of immune checkpoints (PD1, LAG3) and reduced antigen-presentation markers (HLA-DRB, B2M), with distinct spatial distributions in tumors and surrounding microenvironments. Multiplex immunofluorescence demonstrated features of an exhausted CD8⁺ T cell compartment, including enrichment of PD1intLAG3⁻ and PD1intLAG3⁺ subpopulations, and a significant accumulation of myeloid-derived suppressor cells (CD11b⁺ HLA-DR⁻ CD33⁺). CONCLUSIONS:Melanoma in PLWH is associated with distinct clinical and immunological features, including delayed ICI treatment, reduced survival, and an immunosuppressive microenvironment with exhausted CD8⁺ T cells and expanded myeloid-derived suppressor cells. These findings suggest that chronic HIV infection may impair antitumor immunity in melanoma. Targeting the pathways identified here may improve therapeutic responses and outcomes in this population.
PMID: 41504629
ISSN: 1557-3265
CID: 5981192
