Research

Many human diseases are a result of either a deficit or surfeit in the quantity or functionality of particular cell types. Although the principles of cell fate specification during embryogenesis are rather well documented, it is unclear what mechanisms are used to maintain cell identity and appropriate cell numbers in adult tissues. While the cell autonomous molecular processes defining cell states in both physiological and pathological conditions are being defined with increasing precision using genome-wide inventories, the question of when and how individual cell types interact with one another to maintain their identity remains largely unresolved. In this context Tata lab studies:

i) Defining the cellular heterogeneity and the lineage hierarchies in epithelial tissues

ii) How do individual cells maintain their identity under steady state conditions and in the context of regeneration?

iii) The genetic and epigenetic basis of tissue plasticity associated with regeneration and tumorigenesis

To address these questions, we utilize mouse genetics, human donor tissue, a wide array of microscopy techniques, 3-dimensional cell culture, next generation sequencing technologies, and computational biology to study the behavior of tissues at single cell level. Using these tools, we are constantly expanding our knowledge of lung composition, lung repair, and stem cell behavior!

Organoids provide excellent models for studying organogenesis, regeneration and disease. To fully understand molecular and cellular mechanisms regulating the proliferation, maintenance and differentiation of alveolar cells we developed a chemically defined culture conditions for human and mouse alveolar organoids.   Cultured organoid cells in our newly developed media condition retain ultrastructural and molecular features of their in vivo counterparts, as well as self-renewal and differentiation potential over extended passages, and the ability to regenerate functional stem and differentiated cells when engrafted into damaged lungs in vivo. Thus, our organoid system offers a model for pharmaco-genetic screenings, disease modeling and cell-based therapies. Now, we are exploring how different matrix factors influence alveolar organoids formation. Moreover, we are interested in uncovering the interaction of different cell types in our organoid system.

We use single-cell and single-nucleus sequencing to resolve the lung one cell at a time, capturing the full diversity of epithelial, mesenchymal, immune, and endothelial populations that conventional bulk approaches often miss. Beyond cataloging cell types, we apply lineage-tracing technologies to follow individual cells and their descendants over time, revealing how cell families arise during development, injury, and repair. We pair these transcriptomic and lineage readouts with chromatin-based approaches that map the regulatory regions active in each cell and connect them to the genes they control through the three-dimensional folding of the genome. Together, these methods let us catch transitional and rare cell states as they emerge and uncover the gene-regulatory programs that drive lung cell identity in health and disease.