In April, we welcomed 167 on-site and virtual participants for the brand new EMBO | EMBL Symposium ‘Sex differences in health and disease‘. Leading scientists from around the globe convened in Heidelberg to explore topics including sex hormone regulation of health and immunity, genetic differences leading to disease, and mosaicism.

The programme featured two keynote speakers and 16 invited speakers, who guided participants through the molecular underpinnings of sexual dimorphisms, how sex hormones regulate sexually distinct phenotypes, and the role of sex differences in metabolism, infections, cancer, cardiovascular, and neurodegenerative diseases.

The symposium also showcased 66 posters, offering a broad snapshot of current research in the field. Three poster prize winners were selected, and we are happy to introduce you to them in this post.

Sex-based differences in enfortumab vedotin efficacy and NECTIN-4 expression in metastatic urothelial cancer

Presenter: Ithai Waldhorn

Authors: Tarek Taha, Ayelet Alpert, Jalal Baranseh, Alessandro Rizzo, Enrique Grande, Joaquim Bellmunt, Sebastiano Buti, Francesco Massari, Shilpa Gupta, Fernando
Sabino Marques Monteiro, Ravindran Kanesvaran, Giandomenico Roviello, Cristian
Lolli, Yüksel Ürün, Hideki Takeshita, Avivit Peer, Aristotelis Bamias, Ithai Waldhorn

Abstract:

Sex-based differences in cancer outcomes are well documented across tumour types and treatment modalities, yet little is known about whether they influence the efficacy of antibody drug conjugates (ADCs). We conducted a retrospective, international real-world outcome analysis of 454 patients with metastatic urothelial carcinoma (mUC) treated with enfortumab vedotin (EV) across 50 centres in 18 countries, using data derived from the ARON2-EV dataset. Male patients demonstrated significantly longer overall survival (median OS 13.6 vs 7.7 months; HR 0.53, 95% CI 0.37–0.77) and time on treatment compared to female patients, across multiple clinicopathological subgroups. Female patients experienced higher rates of primary resistant disease despite similar baseline characteristics. Analysis of NECTIN-4 expression, the target of EV, in urothelial cancer samples from the TCGA database revealed significantly higher expression in tumours from male patients. This difference remained significant after adjusting for molecular subtype. NECTIN-4 was associated with the estrogen response pathway, which was modulated by smoking in a sex-specific manner. These findings may suggest that sex-related differences in target expression and hormonal signalling affect EV efficacy in UC and may influence its efficacy across tumour types. Prospective studies should consider systematically incorporating sex as a biological variable in ADC research to optimise treatment strategies for both male and female patients.

Due to the confidentiality of the unpublished data, we cannot share the poster.

Decoupling sex chromosome and sex hormone regulation of cardiac myofibroblast activation on phototunable hydrogels

Presenter: Rayyan Gorashi

Authors: Rayyan Gorashi, Kati Richter, Meaghan Loud, Arthur Arnold, Brian Aguado

Abstract:

Heart disease is the leading cause of death globally among males and females. In heart failure (HF), females account for 50% of cases yet have worse clinical outcomes compared to males. Currently, there is a large gap in our understanding of the sex specific mechanisms driving HF. Ovariectomized female mice displayed larger myofibroblast-induced infarct areas after myocardial infarction injury compared to gonadally intact mice, indicating female sex hormones protect against myofibroblast activation. Dissecting the complexity of sex chromosome and sex hormone regulation of myocardial fibrosis will improve our understanding of how each variable contributes to its progression. We hypothesise that both sex chromosomes and sex hormones partially regulate sex-specific myofibroblast activation in response to microenvironment stiffness. To achieve this, we describe a bioinspired hydrogel platform to interrogate the cardiac fibroblast (CF) to myofibroblast transition.

CFs were isolated from adult Four Core Genotype mice [XY & XX males (XYM, XXM), XY & XX females (XYF, XXF)]. CFs were cultured on soft and stiff poly(ethylene) glycol norbornene hydrogels (Elastic Modulus ~ 6 kPa and ~ 50 kPa) and gelatin-coated glass (~ 1 GPa). After 3 days in culture, we immuno-stained alpha smooth muscle actin (α-SMA) for myofibroblast activation and SMAD2/3 inflammatory transcription factor. Statistical significance was determined using Cohen’s d-test and multi-way ANOVAs. We also assessed the relative expression of key myofibroblast genes, including ACTA2, FN, COL1A1, COL3A1, and TGFB1. Statistical significance was determined using multi-way ANOVAs.

Our data show that XYM and XYF CFs exhibit higher levels of aSMA activation on soft and stiff gels, relative to XXM and XXF, which exhibit higher levels of inflammatory SMAD2/3 nuclear localisation. Interestingly, XXF CFs show the highest relative expression of myofibroblast genes. We aim to continue to investigate X-linked mechanisms of TGFB1-mediated myofibroblast activation via SMAD2/2 localisation. Upon separating by gonadal sex and sex chromosome combination, we begin to reveal different molecular mechanisms in how XY and XX sex chromosomes activate in microenvironments of different stiffnesses. Ongoing work seeks to identify the in situ transcriptomic profile of CFs.

View poster

Transcriptomic profiling of telomerase-deficient mice uncovers sex-specific signatures across major organs

Presenter: Alessia Karasani

Authors: Daniel Andergassen, Alessia Karasani, Erika Hilbold, Christian Bär

Due to the confidentiality of the unpublished data, we cannot share the abstract or poster.

The EMBO | EMBL Symposium ‘Sex differences in health and disease‘ took place from 27 – 30 April 2026 at EMBL Heidelberg and virtually.

To learn more about the event highlights and key topics explored, read our event reporter blog post.