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Sladky Lab

Research

Most cells in our bodies are diploid, carrying two copies of each chromosome—one from each parent. Occasionally, cells undergo whole-genome duplication, gaining extra copies of all their DNA in a state called polyploidy. While common in plants and some animals, polyploidy is rare in mammals and typically appears in certain organs, or during aging and disease. Why some tissues can tolerate these cells—and what roles they play in healthy organs—remains unclear.

Polyploidy can alter how cells grow, divide, and respond to stress, but it’s not known how these changes affect living mammalian tissues. In some tissues, polyploid cells appear after injury where they affect regeneration and may even drive scarring, suggesting they actively influence their environment. Why some tissues can tolerate polyploid cells—and what roles they play in healthy organs—remains unclear.

We study where polyploid cells form, why certain cell types and tissues can tolerate extra DNA, and how these cells influence their surroundings. Using advanced microscopy, flow cytometry, and omics approaches in genetic mouse models and 3D organoid systems, we investigate how polyploidy shapes healthy and diseased tissues across ages and sexes—and how understanding these cells could lead to new ways to treat diseases.

In addition, we study centrosomes across mammalian tissues, with a focus on polyploid cell types. Centrosomes are small organelles that organize microtubules, form the poles of the mitotic spindle, and template the assembly of cilia. Because centrosome numbers must be tightly controlled for accurate cell division, their dysregulation can promote genomic instability and cancer. Moreover, centrosomes function as signaling hubs that control the proliferation of cells with extra centrosomes, such as polyploid cells.

Figure 1: Examples of physiologically polyploid cell types across the human body (adapted from Sladky et al., 2021 Journal of Hepatology)
Figure 2: Immunofluorescence microscopy image of naturally polyploid hepatocytes. Centrosomes are visualized by Centrin-GFP (red) and immunostaining of CEP164 (yellow). Nuclei are stained with Dapi (blue) and cell boundaries are marked by ZO-1 (cyan).

Current team

PI:
Valentina Sladky

MSc students:
Esra Engin
Sarah Tepfer

Publications

https://pubmed.ncbi.nlm.nih.gov/?term=valentina+sladky&sort=date