Rajan Dighe



Lab: GB02
Email: rdighe at iisc dot ac dot in
Phone: 91-80-22933261

The research activities of the laboratory of Prof. Dighe are combination of basic and translational research. The principal objective of the laboratory is to study the mechanism of receptor activation with emphasis on the glycoprotein hormone-receptor interactions.Recently, the laboratory has also been investigating the mechanism of “Notch” activation.These studies involve a very interesting approach of using polyclonal, monoclonal and recombinant antibodies against both hormones and their receptors to elucidate the molecular details of hormone-receptor interactions and receptor activation. The translational potential of these studies is evident from the observations that the antibodies against glycoprotein hormone receptors can be used to treat conditions such as precocious puberty or infertility caused by either “gain/loss of function” mutations in the receptors. Similarly, it was demonstrated that an antibody specific for the “gain-of-function” of Notch receptor associated with T-ALL can be used treat hematological cancers. The same antibody, in combination with chemotherapeutic drugs, can be used to treat a variety of cancers. Presently, the laboratory is characterizing recombinant antibodies against different domains of Notch with the hope of developing potential cancer immunotherapeutics. The other research interests of the laboratory are development of novel immunization strategies for human and animal vaccines, gene expression during spermatogenesis and biotechnology of gonadotropins.
  1. A Monoclonal antibody against human Notch1 Ligand binding domain depletes subpopulation of putative breast cancer Stem-like Cells. Sharma et al, Molecular Cancer Therapeutics, 11, 77-86, 2012
  2. The hinge region of human Thyroid-Stimulating Hormone (TSH) Receptor operates as a tunable switch between hormone binding and receptor activation. Majumdar and Dighe, PLoS ONE 7(7):e40291, 2012
  3. The antibodies against the computationally designed mimic of the Glycoprotein hormone receptor transmembrane domain provide insights into receptor activation and suppress the constitutively activated receptor mutants. Majumdar et al, Journal of Biological Chemistry, 287: 34514-34532, 2012
  4. Antibodies against the Extracellular Domain of Human Notch1 Receptor Reveal the Critical Role of EGF Like Repeats 25-26 in the Ligand Binding and Receptor Activation. Sharma et al, Biochemical Journal, 449(2):519-30, 2013
  5. A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors. Sharma et al, Scientific Reports. 5, 11012; doi: 10.1038/srep11012 (2015)