Doublecortin-like kinases (DCLK1, DCLK2 and DCLK3) are implicated in many cancers and neurological disorders. DCLK1 and DCLK2, classified as Microtubule-Associated Proteins, play a critical role in regulating the assembly of microtubules, major components of the cell cytoskeleton.
We uncovered that DCLK1 enzymatic activity is a critical driver of microtubule assembly (Patel et al., Structure 2016, 24(9):1550-61) and used structural biology to guide the design of a DCLK1 selective compound to investigate its role in cancer. In contrast to DCLK1, the role of DCLK2 and DCLK3 is less understood.
We aim to uncover the function of the DCLK family by using a combination of biochemistry, cell biology, structural biology, imaging and chemical biology. This research will provide the basis for developing a novel class of compounds that therapeutically target the DCLK family.
Our laboratory studies protein kinases, an evolutionarily conserved family of proteins that play a significant role in regulating every aspect of the cell function, including growth, differentiation and cell death. Protein kinases, through their catalytic activity, transfer a phosphate from ATP to a target protein, thus modifying the function of other proteins in the cell. Hence, mutations in protein kinases or their abnormal levels are the underlying cause of many human diseases, including developmental disorders and cancer, making them targets for therapy.
We employ a multidisciplinary approach including kinase biochemistry and biology, structural biology (X-ray crystallography and cryo-electron microscopy), assay development, high-throughput screening, proteomics, imaging and chemical biology to gain high-resolution insights into kinase/pseudokinase signaling proteins.