Lempradl
Laboratory

Projects

Early development is a uniquely dynamic period, during which cell fates are determined, organs form, and plasticity is at its peak. Our work is guided by the idea that metabolism is not merely a passive supplier of energy and building blocks, but an active, instructive layer of developmental regulation. By mapping when and how key metabolic transitions unfold, and how they are perturbed by environmental exposures, we aim to identify the mechanisms through which developmental trajectories are established and modified.

There are three major project areas in the lab:

Developmental programming by maternal nutrition: How does maternal obesity lead to embryonic reprogramming?

The conceptual foundation for this work draws on earlier studies by Dr. Lempradl and others demonstrating that the parental environment, particularly nutrition, can influence offspring phenotype in the absence of direct genetic changes. Building on this, the lab became interested in how the maternal metabolic environment, specifically obesity, might precondition the embryo through oocyte-derived cues.

To examine how maternal obesity alters the metabolic and transcriptomic programming of the oocyte and early embryo, we apply our single-embryo multi-omics approach. Additionally, the lab investigates how these cues might interact with genetic predisposition to disease. By identifying modifiable pathways that mediate maternal effects on development, this research opens the door to translational strategies aimed at prevention or mitigation, particularly in the context of rising global rates of maternal obesity and metabolic dysfunction.

Environmental toxicants and paternal programming: How do environmental toxicants alter developmental programming and metabolic health across generations?

This project addresses a critical gap by investigating how environmental exposures, particularly through the paternal germline, alter developmental programming in ways that predispose offspring to disease. Our integrative approach combines high-throughput discovery and mechanistic analysis in Drosophila, where genetic tools and rapid generation times enable detailed interrogation of causal pathways, and complements these studies with targeted validation in mouse models. This provides a powerful and cost-effective platform to identify, prioritize and characterize environmental exposures with intergenerational consequences.

Our goal is to identify transcriptional signatures and disrupted developmental pathways in embryos derived from exposed fathers, with a focus on genes linked to metabolic regulation, epigenetic remodeling and stress responses. These data will be integrated with small RNA and sperm epigenome profiling from the same exposure model, providing a comprehensive view of how paternal exposure reprograms embryonic development at multiple molecular levels. Longer term, we aim to expand this approach to other toxicants identified in our high throughput Drosophila model and further refine cross-species comparisons of conserved early-response pathways.

High-resolution view of developmental metabolism: Developing the tools and baselines needed to understand metabolism in early development.

A defining feature of my lab has been our focus on developing the tools needed to understand metabolism in early development, a biologically complex window that is difficult to access experimentally. The investment in building these methods is strategic: it allows us to define how metabolism unfolds during normal early development and study reprogramming in the project areas described above. We recently established a single-embryo multi-omics platform that combines RNA-sequencing and metabolomics in individual Drosophila embryos. This system was designed to treat development as a continuous molecular process rather than a series of morphologically defined stages. By pairing transcriptomics and metabolomics in the same embryo, we not only provide descriptive maps but also generate mechanistically informed hypotheses about how metabolites act as signals that shape developmental trajectories.

Beyond its technical value, this work advances a conceptual shift in how metabolism is viewed in development. Traditionally seen as supportive, metabolism is emerging as an active organizer of embryogenesis. As interest grows in the link between early metabolism, environmental exposures and disease susceptibility, advancing our technology platform ensures that the lab remains positioned at the forefront of both methodological and conceptual innovation. The tools and datasets we have built not only support our own research trajectory but offer broad utility across model systems and disciplines, opening new avenues for mechanistic discover and translational impact.