DMM Journal

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Disease Models & Mechanisms - discovery for human health. A @biologists.bsky.social Open Access journal that publishes human disease research.

Innovative Preclinical Models for Pediatric Cancer Research Date: 13 – 15 October 2026 Location: Nationwide Children’s Hospital Conference Center, Columbus, Ohio, USA Organisers: James Amatruda, Pratiti (Mimi) Bandopadhayay, Ana Banito and Elaine Mardis
Cardiac tissue slice showing optically mapped activation and color-coded calcium and voltage maps from a pacing site and spheroid grafts, associated CaT/Vm time traces, and immunofluorescence of the graft–host border with nuclei (DAPI), Connexin43, and sarcomeric α-actinin.
Call for papers: Special Issue "Paediatric Genetic Diseases: Models, Mechanisms and Therapies" edited by James Amatruda, Ross Cagan and Elaine Mardis — submission deadline 2 November 2026; journal logo with colorful fluorescent microscopy of tissue.
Scientific poster summarizing in vitro and in vivo models for androgenetic alopecia drug development, showing hair follicle morphogenesis, cell populations, 2D/3D cultures, organoids, organ culture, evaluation assays, and advantages/disadvantages of each model.
Immunofluorescence panels showing iPSC lines stained for pluripotency markers SSEA4, OCT4, NANOG and SOX2 (yellow) with DAPI nuclear counterstain (blue); merged panels show nuclear marker co‑localization in TG and WT lines and minimal signal in negative controls.
Fluorescent micrographs (red) and scatter plots comparing cilia morphology and function across PBS, HTS post‑treat, NAC post‑treat, and NAC co‑treat with MPO: red-stained cilia images at left and quantified median cilia velocity and beat frequency at right, with significance markers.
Schematic framework showing testable interface nodes labeled A, B, C across model scopes (multi-lineage, assembleoid, self-patterned) and three inquiry levels—breakpoint mapping, coupling directionality (uni/reciprocal), and multi-node interaction (additive vs non-additive perturbation outcomes).
Neuronal cultures stained for nuclei (blue), total TAU (green), phospho‑T212 TAU (red), and MAP2 (gray) shown as merged panels across treatments (DMSO, LCTB‑21, iso‑LCTB‑21) in control and T21 rows, with a bar graph quantifying normalized pT212 fluorescence.
Head shot of Hans Clevers
Editors Vivian Li, Austin Smith and Joseph Wu (left to right)
Journal cover for Disease Models & Mechanisms showing fluorescent microscopy of tissue with clustered blue, yellow, and magenta-stained cells highlighting cellular structures; text notes a special issue on in vitro models of human disease to inform mechanism and drug discovery.
Call for papers: Special Issue "Paediatric Genetic Diseases: Models, Mechanisms and Therapies" edited by James Amatruda, Ross Cagan and Elaine Mardis — submission deadline 2 November 2026; journal logo with colorful fluorescent microscopy of tissue.
Speakers James Amatruda Children’s Hospital Los Angeles, USA Pratiti (Mimi) Bandopadhayay Harvard Medical School, USA Ana Banito DKFZ German Cancer Research Center, Germany Elaine Mardis Nationwide Children’s Hospital, USA Delilah Hendriks Princess Máxima Center, The Netherlands Caroline Hutter St. Anna Children’s Cancer Research Institute, Austria Kevin Jones The University of Utah, USA Genevieve Kendall Nationwide Children’s Hospital, USA Claudia Kleinman McGill University, Canada Verena Korber University of Oxford, UK Lena Kutscher Hopp Children’s Cancer Center Heidelberg (KiTZ), Germany Timothy Phoenix University of Cincinnati, USA Martine Roussel St. Jude Children’s Research Hospital, USA Alice Soragni University of Colorado Anschutz, USA Joelle Straehla Seattle Children’s, USA Eleni Tomazou St. Anna Children’s Cancer Research Institute, Austria Michael Underhill University of British Columbia, Canada Michelle Wedemeyer Nationwide Children’s Hospital, USA Marc Zuckermann Hopp Children’s Cancer Center Heidelberg (KiTZ), Germany
A conference flyer titled “4th Metabolism in Health & Disease,” with the subtitle “Understanding the Role of Metabolism in Aging, Physiology & Disease.” The event is on 10–13 October 2026 in Lisbon, Portugal. The conference chairs are: Anna Krook, Karolinska Institute; Christian Metallo, The Salk Institute; and Peter J. Mullen, University of Southern California. Confirmed invited speakers are: Janelle Ayres, The Salk Institute; Donita Brady, University of Pennsylvania; Navdeep S. Chandel, Northwestern University; Ed Chouchani, Dana-Farber Cancer Institute; Heather Christofk, University of California, LA; Katrien De Bock, ETH Zürich; Mark Febbraio, The Baker Heart & Diabetes Institute; Javier Garcia-Bermudez, UT Southwestern; Brian Kennedy, National University Singapore; Natalie Krahmer, Helmholtz Zentrum München; Lydia Lynch, Princeton University; Thales Papagiannakopoulos, NYU School of Medicine; Florian Rosenberger, Karolinska Institute; Anu Suomalainen Wartiovaara, University of Helsinki; Jessica Spinelli, Dana-Farber Cancer Medical School; Christian Metallo, The Salk Institute; Chris Church, Francis Crick Institute; Mark Kelly, University College Dublin; Bing Zhang, Westlake University.
Multi-panel figure showing lateral views of mouse embryos at embryonic days E12.5, E13.5, and E14.5, arranged in rows and columns (panels A–O). Embryos have been stained with X-gal blue to detect β-galactosidase, which signifies Cre expression and thus active DUX4 regulatory elements. Each row corresponds to a developmental stage, and columns compare different genotypes: reporter-only controls (A, F, K) with little or no blue staining; ACTA1-cre controls (B, G, L) showing widespread blue staining throughout skeletal muscle; and three transgenic insertion lines (#6, #7, #11; panels C–E, H–J, M–O) with localized X-gal blue staining. In transgenic embryos, blue signal appears in forelimbs (white arrows), hindlimbs (red arrows), and facial regions near the lip corner/zygomaticus (red arrowheads). Staining intensity and distribution increase with developmental stage. A scale bar indicates 1 mm.
Schematic overview of the molecular features modeled in the knock-in HTT minipig (KI-85Q-HD). The KI-85Q-HD minipig recapitulates key molecular hallmarks of Huntington's disease: somatic CAG repeat instability and alternative processing of HTT pre-mRNA. (1) A (CAG)82CAA(CAG)2 repeat was introduced into the endogenous porcine HTT locus by CRISPR/Cas9 editing of exon 1. (2) The expanded allele undergoes tissue-specific and age-dependent somatic CAG repeat expansion, with the largest changes detected in the caudate nucleus, kidney and spleen. (3) Full-length HTT mRNA is translated into full-length HTT protein, while activation of a cryptic polyadenylation site (asterisk) within intron 1 generates the HTT1a transcript, which encodes the short, aggregation-prone HTT1a protein.
An illustration of a mouse running in a wheel with the title that reads: 'Animal behaviour and cognition'.
Top image is a wildtype zebrafish embryo at 4 days post fertilisation. Bottom image is a zebrafish embryo that has a maternal zygotic homozygous mutation in the folate receptor, also at 4 days post fertilisation. Without any drug exposure, the folate receptor mutant embryos display phenotypes such as cardiac edema and curved tails with ventral thickening.
Photo of Liz and Jay Scott
A multi‑panel scientific figure showing transcriptome changes in Cstb−/− mouse brains across development. Panel A displays bar charts of the number of significantly differentially expressed genes in cerebellum, cortex, and hippocampus at postnatal day 14 and at 1, 3, and 6 months. Panel B contains Venn diagrams illustrating the overlap of significant genes between the three brain regions. Panels C–E show UpSet plots for cerebellum, cortex, and hippocampus, with bar charts indicating the number of shared significant genes across time points and dot matrices marking the combinations. Green boxes highlight genes consistently altered across all time points in cerebellum and cortex, and from 1 month onward in hippocampus. Labels include CB (cerebellum), CTX (cortex), and HC (hippocampus).
A two‑panel illustration showing how the circadian clock regulates immune function. Panel A depicts the brain’s central clock: light enters the retina and entrains the suprachiasmatic nucleus, which sends rhythmic signals to the paraventricular nucleus. From there, signals regulate hormone release through the HPA axis, autonomic nervous system output, and melatonin secretion. These cues, together with sleep–wake, activity, and feeding rhythms, synchronize peripheral clocks in organs. The right side shows the cellular clockwork: BMAL1 and CLOCK activate PER, CRY, REV‑ERBs, and DBP; PER and CRY repress BMAL1/CLOCK; REV‑ERBs and RORs compete to regulate BMAL1 and NFIL3; NFIL3 and DBP regulate D‑box–controlled genes. Positive and negative feedback loops are highlighted in red and blue. Panel B shows the timing of key circadian immune processes in mice, with peak phases indicated and numbered references marking supporting studies.
A multi‑panel structural map of the RET extracellular domain highlighting residues linked to Hirschsprung’s disease. Panel A shows 43 co‑receptor–interacting residues as purple spheres, with four disease‑associated mutations marked by arrows. Panel B shows 24 ligand‑interacting residues as blue spheres, with one mutated position indicated. Panel C shows 19 calcium‑binding residues as light‑green spheres, with three mutated positions marked. Panel D shows 222 buried core residues as brown spheres, with 36 mutated positions labeled. Panel E highlights 14 residues that stabilize RET structure through hydrogen bonds, salt bridges, or disulfide bonds, shown in shades of pink and olive, with arrows marking disease‑linked mutations. Panel F shows six positions involving proline or glycine substitutions that destabilize the structure, displayed as teal spheres with arrows.
An illustration showing a spectrum of model systems used to study human disease.
A schematic representation of the experimental design of the in vivo study showing the steps of microbiota alterations. 1. Microbiota was depleted on days 0-14 by administration of drugs, and samples were taken on day 15. 2. Microbioata was reconstituted throughout days 16-36, and the samples were taken on day 36. 3. Experimental autoimmune encephalomyelitis was induced after day 37 and monitored until day 67.
photo of poster prizes winners with their certificates
Study design showing analysis of patient bone‑marrow samples by nestin and CXCL12 immunohistochemistry and RNA expression. Images include low nestin staining in a control sample and high nestin staining in severe aplastic anaemia. Bar plot and summary table display quantified nestin levels across 48 samples, including moderate, severe, and very severe aplastic anaemia groups.
Diagram and images showing how the Cdx2cre/+;Pax3fl/fl mouse model of spina bifida is generated. A schematic illustrates the genetic cross in which Cdx2cre drives Pax3 knockout in the body while the head remains wild type. Embryos at E10.5 and E15.5 show body‑restricted reporter expression, with a small unrecombined region at E10.5 and the fetal outline marked at E15.5. Representative E15.5 control and mutant fetuses are shown, with white arrowheads marking the open spina bifida lesion in the mutant. A developmental timeline summarizes progression of the defect, with dashed lines indicating the extent of the open lesion.
Confocal and cytokine‑analysis images from mouse peritoneal inflammation experiments comparing wild‑type and mNLS IL‑1α mutant mice. In the LPS‑injection model, wild‑type peritoneal cells show nuclear pro‑IL‑1α staining, while mNLS cells lack nuclear signal; pro‑IL‑1β remains cytosolic in both genotypes. Quantification plots show nuclear localisation levels for IL‑1α and IL‑1β. In the LPS+ATP model, cytokine measurements from peritoneal lavage and plasma demonstrate similar release of IL‑1α, IL‑1β, IL‑6, and TNF between wild‑type and mNLS mice. Schematics illustrate both injection models.
Pathology images of patient‑derived xenograft (PDX) tumour samples stained for E‑cadherin, p120, ER, PR, and HER2. A pathologist identified seven PDX models as invasive lobular carcinoma (ILC), with one model (CTG‑3434) classified as mixed no‑special‑type/ILC. Additional non‑special‑type PDX samples are shown for comparison.
Whole‑mount in situ hybridization images showing ctsz expression in zebrafish larvae. Uninjured larvae display ctsz‑positive cells near the heart cavity, intestinal bulb, and mid‑intestine. A tailfin‑injury schematic marks the region analyzed. Comparative images of wild‑type larvae show minimal staining when uninjured and increased ctsz signal at the wound site after injury, including staining in individual recruited leukocytes.
Zebrafish larvae showing zebrin II–positive Purkinje cells across control, non‑pathogenic (AUUUU)₇, and pathogenic (AUUUC)₅₈ RNA conditions. Diagram outlines embryo injection and immunofluorescence workflow. Representative z‑projection images display similar Purkinje cell patterns across groups. Quantification plots show no significant differences in Purkinje cell volume or mean zebrin II intensity
Microscopy images showing glomerular microthrombi in the kidney cortex of mice treated with medium‑chain or long‑chain polyphosphates (P100 or P700), alone or combined with LPS. (A) Masson’s trichrome staining highlights red fibrin deposits and blue collagen deposits within glomerular capillary loops, most prominent in P700 and LPS+P700 groups. (B) Immunofluorescence images show red CD61‑positive platelets accumulating in glomeruli and arterioles, with green LTL marking proximal tubule brush borders and blue Hoechst staining nuclei. Insets display individual and merged channels. (C) High‑magnification immunofluorescence shows red von Willebrand factor–positive deposits in glomerular capillary loops of P700 and LPS+P700 mice, with green nephrin showing a granular podocyte pattern and blue Hoechst‑stained nuclei.
Figure illustrating a workflow to measure neuronal activity in C. elegans using GCaMP6m fluorescence and microfluidic immobilization. A: Confocal images of a 4‑day‑old worm expressing pan‑neuronal GCaMP6m, shown at whole‑animal and head‑region magnification. B: Diagram of the PDMS microfluidic device that straightens and traps worms for imaging, with a magnified view of animals inside the channels. C: Overview of the workflow: imaging age‑synchronized animals, quantifying GCaMP6m fluorescence from snapshots, and normalizing values using GCaMP6m protein levels measured by western blot. D: Violin plot showing reduced neuronal GCaMP6m fluorescence in unc‑13 mutants compared with controls. E: Scatter plot showing lower GCaMP6m protein levels in unc‑13 mutants. F: Violin plot of fluorescence normalized to protein levels, again showing reduced neuronal activity in unc‑13 mutants.
A figure showing transcriptomic and proteomic differences caused by chd7 loss. Panels A and B display principal component analyses: panel A separates RNA samples by genotype and replicate, and panel B shows similar separation for protein samples. Panels C and D show heatmaps: panel C presents clustered log2‑scaled expression of 1,780 differentially expressed genes, and panel D shows clustered expression of 553 differentially expressed proteins. In both heatmaps, heterozygous and homozygous mutants are visually distinct from wild‑type samples.
Time‑lapse and confocal images of zebrafish larval skin show that xylazine treatment rapidly induces keratinocyte extrusion, tissue‑wide contraction of the post‑anal fin fold, and disruption of basal keratinocyte adhesions. Bright‑field panels highlight increased extrusions and fin‑fold contraction compared with controls, while reporter‑line fluorescence images show keratinocytes leaving the epidermis and selective disorganisation of the basal layer. Quantification plots display increased extrusion events and reduced fin‑fold area after xylazine exposure, with partial rescue by para‑aminoblebbistatin. Additional imaging of F‑actin dynamics reveals loss of intercellular adhesions and eventual de‑adherence of neighbouring basal keratinocytes.
A schematic shows the workflow for isolating and immortalising postnatal RFP‑positive cardiac stromal cells from Wt1GFP/+;Wt1Cre;ROSA26‑tdRFP mice, excluding endothelial (CD31+), hematopoietic (CD45+), and highly GFP‑expressing cells. Adjacent bright‑field images display primary and immortalised RFP‑positive cardiac cells. Additional immunofluorescence panels show strong vimentin expression in immortalised cells and patches of α‑SMA–positive cells visualised with α‑SMA (green) and phalloidin (red).
Multi‑panel figure illustrating effects of reducing mutant huntingtin in striatal somatostatin interneurons (SST‑INs). (A) Diagram of AAV9‑SST‑eGFP injection site in the mouse striatum for control, BACHD, and BACHD/SST‑Cre genotypes. (B) Confocal images show SST‑INs expressing eGFP (green) and SST immunolabeling (red), confirming targeted expression; nuclei in blue; 10 µm scale bar. (C) Scatter/violin plot shows higher spontaneous firing rates in BACHD SST‑INs compared with controls, with firing normalized in BACHD/SST‑Cre mice; points indicate mice and lines the median. (D) Example color‑coded traces of spontaneous firing. (E) Cumulative distributions of inter‑event intervals show increased inhibitory synaptic event frequency in BACHD/SST‑Cre SST‑INs. (F) Cumulative distributions of inhibitory postsynaptic current amplitudes show reduced amplitudes in BACHD mice and normalization in BACHD/SST‑Cre mice. (G) Example inhibitory synaptic current traces. (H) Amplitude–frequency histograms
Domain architecture of the heat shock transcription factor (HSF) family of transcription factors. All somatic HSF proteins contain an amino-terminal, winged helix-turn-helix DNA-binding domain (DBD). Downstream of the HSF1, HSF2 and HSF4 DBDs are heptad repeat (HR) regions (HR-A/B) that form the leucine zipper (LZ) domains, with LZ1-3 required for HSF oligomerization. A third HR region (HR-C), which forms LZ4, suppresses HSF activity through intramolecular interactions with LZ1-3 in HSF1 and HSF2. Transcriptional activity for some HSFs requires the activation domain (AD). Sequence similarity was determined using Clustal Omega Multiple Sequence Alignment with protein amino acid sequences obtained from Ensembl. Sequence similarity is scored from 0 to 10, which is indicated by the height and color of the bars under the respective HSF diagrams.
Figure showing experimental set-up for ototoxicity study, demonstrating that vibratome sectioning preserves otic vesicles. Panel A illustrates vibratome sectioning of day‑75 IEOs into ~200 µm slices, followed by 48 h recovery and 24 h drug treatment at day 77. Sections were fixed were fixed at 1, 3 or 7 days after treatment. (B) Side-view representative image of an IEO sectioned into 200 µm-thick slices. (C) Top-view representation of a vibratome slice of an IEO, with arrowheads annotating the otic vesicles (inset). Scale bars: 100 µm and 500 µm. (D) Intact morphology of an otic vesicle without vibratoming (I), directly after vibratoming (II) and after 48 h recovery (III), showing Hematoxylin and Eosin (H&E) histological staining, followed by immunofluorescent staining of otic epithelium [CDH1+ (green)/SOX10+ (cyan)] and of otic vesicles containing hair cells (MYO7A+, yellow), neurons (TUBB3+, magenta) and cell nuclei (DAPI+, dark blue). In III, the apparent MYO7A–TUBB3 colocalization likely reflects immature hair cell precursors that transiently co-express neuronal β-III-tubulin during development. Scale bars: 25 µm.
Photo of Muhammad Dimas Reza Rahmana
Histological staining and immunofluorescence of the in vitro endometriosis model. Attachment of endometrial (E) to peritoneal (P) constructs is observed after 3 and 10 days of culture (top and bottom row, respectively). The endometrial–peritoneal interface (EPI; dotted line) was composed of cells expressing cytokeratin (CK) and CD10, with some endometrial stromal cells, the CD10-positive cells, appearing to migrate to the peritoneal compartment (arrows). Scale bars: 200 µm; 50 µm (insets).
Fluorescent microscopy image of nf1 zebrafish model. Green signals represent increased pERK levels in nf1 mutant larvae compared to wild type. Magenta signals denote decreased levels of phosphorylated ERK1/2 (pERK) in nf1 mutant larvae compared to those in wild type.
A promotional graphic for the “4th Metabolism in Health & Disease Conference” on 10–13 October 2026 in Lisbon, Portugal. The theme of the conference is “Understanding the role of metabolism in aging, physiology & disease” and ECR grants of €500 & €1,000 are available. To apply email chloe@fusion-conferences.com with an abstract for a short talk or poster consideration and a summary as to why you would benefit from attending the meeting (further details on website). The abstract submission deadline for talks is 13 April 2026.