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Group Introduction

DAILAB

Introduction to research

Normal somatic cells divide only a limited number of times in culture in contrast to their cancerous derivatives that can go on proliferating forever. Our research interest is to understand the control of cell proliferation in normal cells and its break–down during carcinogenesis. Our goals are set to generate knowledge and reagents to manipulate lifespan of normal and cancer cells in order to achieve healthy longevity and cancer therapeutics. We use human normal and a large variety of in vitro immortalized as well as tumor-derived cells to identify and functionally characterize the role of specific factors in cellular senescence and cancer. We have originally cloned a member of the heat shock family protein, mortalin that is found to perform many vital functions including chaperoning, mitochondrial import and energy generation, and intracellular trafficking. Remarkably, the subcellular distribution of mortalin differs in normal and cancer cells. It is pancytoplasmic in normal and perinuclear in cancer cells. We have demonstrated that mortalin inactivates wild type p53 function in cancer cells and hence is a potential target for cancer therapy. Another p53-regulating protein, CARF was cloned in our group and is shown to be a key regulator of p53 and DNA damage response pathways. It poses a two-way regulation of cell proliferation by interacting with multiple proteins including ARF, p53, HDM2 and p21. Besides validating the functional aspects of mortalin and CARF in cell proliferation controls, our strategies include the manipulation of cellular lifespan to generate long-lived normal cells and short-lived cancer cells. We are set to accomplish these goals from a wider approach that includes identification and functional characterization of proteins, noncoding functional RNAs, peptides, intracellular antibodies and natural products for healthy long life.
Recent progress in the stem cell research has prioritized the refinement of cell labeling techniques for in vitro and in vivo basic and therapeutic studies. We have generated internalizing Quantum dots (i-QDs) by conjugating them with an internalizing anti-mortalin antibody. The i-QDs serve as efficient, genetically noninvasive, non-toxic and functionally inert way to label a variety of cells in culture including cancer cells, stem cells and induced pluripotent stem cells (iPS) for long term in vivo imaging and diagnostics.

Research Technologies

  1. Cell culture techniques for normal and immortal human and mouse cells and their use in biochemical, molecular, genetic and visual assays.
  2. Development of technologies for immortalization of normal human cells.
  3. Development of cancer-therapeutic reagents.
  4. Development of high-resolution imaging techniques for visual examination of protein niches, partners and functions.
  5. RNA-mediated gene regulation and loss-of-function screenings by functional RNAs and intracellular antibodies.
  6. In vitro and in vivo imaging.

Mortalin research for cancer and bio-imaging

Endeavoring to improve the quality of life through research

CARF regulates cellular senescence and transformation

List of Publications

20172016201520142013201220112010

Staff:

  • Renu Wadhwa (Laboratory Leader)
  • Sunil Kaul
  • Koichi Yoshinari
  • Singh Rajkumar