2024 Fellowship Winners

Skin conditions are prevalent and affect millions of individuals. Within the skin, there are a myriad of cell types amongst which the most abundant glia in the peripheral nervous system are Schwann cells (SC). SC are known to play a role in tissue repair, but their involvement in skin diseases like atopic dermatitis, keloids, and psoriasis is not well understood. While early research has begun to explore SC behavior in these conditions, no large-scale study has mapped their diversity across both healthy and diseased skin. This project aims to create a comprehensive single-cell and spatial transcriptomic atlas of human skin SC to better understand their role in health and disease. We will characterize the diversity of SC populations in healthy skin and 23 skin conditions, validate their spatial distribution in situ using spatial transcriptomics and advanced 3D imaging techniques. Additionally, we will identify the spatial niches of SC in the skin and explore their potential roles in disease regulation. The resulting SC atlas will be a valuable resource for understanding and treating conditions like eczema, acne, psoriasis, and cancer. This open-access resource will also accelerate future research on SC biology across different organs, fostering advancements in both clinical and basic dermatological science.

Common abuse substances like alcohol, caffeine, and tobacco are teratogenic agents that can disrupt foetal brain development during gestation. Their effect is studied individually despite their often-combined intake.

The proposed project aims to investigate the synergistic effect of polydrug abuse on foetal brain development using brain organoids. We will use a high-throughput drug screening platform based on diverse genetics, and diverse ethnicity human organoids, all the way to patient-derived samples.

Polydrug exposure will be tested at different stages of brain development up to mid-gestation, according to the developmental window recapitulated in brain organoids. The study will employ refined protocols to ensure high inter-sample reproducibility. Preliminary results with pre-patterning of pluripotent stem cells and morphology-guided quality screening of organoids have been shown to overcome the hurdle of poor sample-to-sample reproducibility.

Using advanced imaging and analysis techniques, the project will assess teratogen impact on neural progenitor proliferation, differentiation, neuronal maturation, and activity. This innovative approach aims to provide insights into the synergistic effect of multiple abuse substances during pregnancy, advancing beyond the traditional single-drug studies.

Pain, while a vital sensory warning mechanism, becomes debilitating in its chronic forms, such as neuropathic pain (NP).

The project aims to elucidate the molecular mechanisms underlying pain chronification and modulation through physical exercise, leveraging cutting-edge single-cell omics and bioinformatics approaches.

This study intends to (1) map transcriptional and epigenetic changes in nociceptors and associated cell types during NP progression, (2) identify molecular pathways activated by exercise during NP, and (3) uncover therapeutic targets for restoring nociceptor function. Ultimately, this work will also serve as a foundational resource for other researchers in the field of pain biology.

A reduction in skeletal muscle (SkMuscle) mass or atrophy, is associated with a decline in independence and quality of life of aged individuals. It is estimated that up to 27% of the global population exhibits some degree of skeletal muscle atrophy. The development of SkMuscle atrophy is influenced by several factors, including natural aging and reduced physical activity.

Despite the initiatives encouraging an active lifestyle as a countermeasure against SkMuscle atrophy and the scientific efforts, there is still no standard therapy against the involuntary loss of SkMuscle mass associated with aging. Hence, new approaches to explore potential novel regulators of SkMuscle atrophy should be considered. Long non-coding RNAs (lncRNAs) are emerging as significant coordinators of SkMuscle physiological processes. Following interventions that induce SkMuscle atrophy, we found a not previously described LncRNA sequence overexpressed in mouse and human skeletal muscle.The objective of this project is to investigate the role of this novel LncRNA in SkMuscle homeostasis and regeneration. To achieve the project objectives, we will use an innovative human model of SkMuscle.

Using human donors SkMuscle stem cells, I developed a SkMuscle 3D model that resembles SkMuscle architecture, responds to physiological signals and regenerates upon stimulation. The Skeletal muscle 3D model will be instrumental to deregulate the expression of the RNA sequence of interest using a viral system of gene transduction. We will evaluate SkMuscle model histology at tissue and transcriptional level.

We will check fiber metabolism, mitochondrial and ribosome function during SkMuscle homeostasis as well as the influence of the LncRNA in the muscle regenerative potential.In conclusion, this research plan will describe the role of non-previously investigate LncRNA on SkMuscle repair and metabolism, a knowledge gap in the field of SkMuscle physiology that we will address with the current research.

My project explores heterophagy, a novel cell-assisted quality control mechanism crucial for tissue homeostasis, with a particular emphasis on its regulatory mechanisms and the impact of aging in this process. This research could lead to new therapies for aging and age-related diseases, helping to improve healthspan and promote healthy aging through immune system modulation.