The Rathod Lab

The Rathod group aims at understanding the fundamentals of epidermal differentiation with a cell-cell adhesion centric view and how these cues are regulated in skin pathologies. Desmosomes are cell-cell adhesion complexes that tether cells and provide mechanical integrity to epithelia and other tissues. Desmosomes play a crucial role in differentiation and desmosome dysfunction causes disorders of the skin, leading to skin fragility and altered differentiation. The role of intercellular junctions (Desmosomes) beyond adhesive roles have been described in recent years, however the underlying mechanisms are only partially understood. Given the importance of cell-cell adhesion in tissue homeostasis and development, gaining mechanistic understanding would provide valuable insights into disease application.

The group aims to:

  • Understand the role of desmosomes in epidermal differentiation and tissue repair.
    The contribution of desmosomal proteins in epidermal differentiation has been studied in past years. We recently identified novel modulators of cell-cell adhesion and epidermal differentiation (Rathod et al., JCB, 2024) . The role of cell-cell adhesion is also demonstrated in the context of tissue repair, however the underlying mechanisms and functional link between desmosomes and epidermal homeostasis and repair is not completely defined. We aim to understand the role of desmosomes in epidermal differentiation and consequently tissue repair.
  • Elucidate the role of desmosomes beyond cell-cell adhesion in the context of skin and associated pathological conditions.
    Epidermal differentiation and tissue repair are complex physiological processes associated with cell state changes, metabolic plasticity, cell-cell interactions and a plethora of complex signaling networks. We here aim to understand the role of desmosomal proteins at the cross roads of these coordinated events.
  • Develop novel therapeutic approaches for diseases with impaired adhesion.
    A potentially life threatening skin disease which is caused due to desmosome dysfunction is the autoimmune condition pemphigus, where autoantibodies target components of the desmosome. This leads to impaired cell-cell adhesion in the epidermis, resulting in severe blistering. Thus finding ways to strengthen cell-cell adhesion could serve as a therapeutic option. Through this study, we aim to establish novel therapeutic options for pemphigus.

In order to address these questions, we use genetic mouse models, 3D reconstructed human epidermis (3D-RHE), epidermal organoids, 2D models and ex-vivo disease models. A combination of cell biology, molecular biology, biochemical analysis, omics, CRISPR screens are used in the lab to address the fundamental questions we ask. These platforms enable us to fulfil our goal to find answers holding potential for new clinical management strategies.