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Principal Investigator

Dr. Sorab Dalal

Principal Investigator

Research Interests

  • Regulation of desmosome formation.
  • Therapy resistance in colon cancer
  • Regulation of cell cycle control and other cellular pathways by 14-3-3 proteins.

 

RESEARCH

There are two major areas of research in the laboratory. The first focuses on the mechanisms by which therapy resistance is acquired in colorectal cancer and developing potential therapeutic approaches to re-sensitize tumor cells to therapy with an emphasis on the contribution of iron homeostasis to therapy resistance. We have demonstrated that while excess intracellular iron might lead to tumor development, in the context of therapy, excessive intracellular iron promotes cell killing due to the generation of reactive oxygen species (ROS). We demonstrated that a novel monoclonal antibody developed by our collaborators, sensitized tumors to therapy and inhibited tumor progression by promoting the retention of iron in the tumor cells. Therefore, iron homeostasis is central to tumor progression, therapy resistance and tumor killing.

Most functions in cells are performed by large protein complexes and the regulation of complex formation is critical to cell homeostasis. The second problem we work on in the laboratory is to elucidate the mechanisms by which the 14-3-3 protein family bind to and dissociate from their protein ligands thereby affecting ligand function. The 14-3-3 family participates in almost every signaling pathway present in mammalian cells which is why we think of them as the answer to the ultimate question of the life, the universe and everything. As part of these studies we wish to determine the molecular basis for specific complex formation between 14-3-3 proteins and their ligands and elucidate their role in the centrosome duplication pathway. These studies have been extended to identify specific ligands for individual 14-3-3 isoforms to determine how individual family members regulate different cellular pathways. This is important as 14-3-3 proteins regulate multiple cellular pathways, analysis of the phenotypes underlying loss of a specific 14-3-3 isoform must consider how different pathways contribute to the observed phenotype.

Ongoing Research Projects

  • Regulation of tumor progression by 14-3-3 proteins

    PLAKOPHILIN3 FUNCTIONS REQUIRED FOR THE INHIBITION OF TUMOR PROGRESSION AND METAST…

    Plakophilin3 (PKP3) is a desmosomal plaque protein that is required for desmosome formation and whose levels are… more

  • Cell cycle and 14-3-3

    REGULATION OF CELL CYCLE CONTROL AND CHECKPOINT FUNCTION BY 14-3-3 PROTEINS

    The purpose of the eukaryotic cell cycle is to accurately duplicate and segregate the genome. Progression throug… more

  • Tissue organization and regulation by 14-3-3

    REGULATION OF TISSUE ORGANIZATION AND DIFFERENTIATION BY 14-3-3 PROTEINS

    Work in the laboratory has led to the development of a novel method for the generation of transgenic animals. US… more

  • tumor progression and 14-3-3

    REGULATION OF TUMOR PROGRESSION BY 14-3-3 PROTEINS

    14-3-3σ is expressed only in cells of epithelial origin and loss of 14-3-3σ has been observed in multiple solid… more

  • Model of the mechanism by which LCN2 promotes therapy resistance and tumour progression.

    Tumor progression and therapy resistance in colon cancer (the role of iron homeost…

    Our previous work demonstrated that loss of the desmosomal plaque protein, plakophilin3 (PKP3), leads to an incr… more

  • Loss of 14-3-3σ leads to the stabilization of c-Jun resulting the induction of an EMT.

    Regulation of the EMT program and therapy resistance by 14-3-3

    Of the seven 14-3-3 isoforms present in mammalian cells most are ubiquitously expressed while some of them exhib… more

  • Cartoon of the regulation of centrosome assembly and duplication by 14-3-3 proteins.

    Regulation of centrosome duplication by 14-3-3 proteins.

    The 14-3-3 protein family in mammals is a conserved set of small acidic proteins that regulate several cellular… more

Lab Members

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Contact

Office Contact

Dr. Sorab Dalal

Sorab’s Laboratory KS 230, Advance Centre for Treatment Research & Education in Cancer, Tata Memorial Centre, (ACTREC), Plot No. 1 & 2, Sector 22, Kharghar, Navi Mumbai-410210. Maharashtra India. +91 (022) 2740 5000/ 6873 5000 Extn-5007Lab Website

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