Welcome to the Laboratory of Sanjai Kumar at Queens College - CUNY
About Research in Kumar’s Laboratory
The research in Kumar’s laboratory spans at the interface of chemistry and biology, and is broadly focused on discovery of unknown enzyme function using chemical biology approaches. More specifically, the enzymes of a critically important signaling event, protein phosphorylation, are currently of primary interest. Some of the scientific methodologies routinely used in the laboratory are: Multi-step synthesis of small molecule inhibitors and biosensors using both classical solution-phase and solid-phase synthetic procedures, enzyme kinetics, assay development, recombinant protein expression and purification, inhibitor screening, development of in vivo cancer model, and structure-based ligand design.
Development of Cell Active and Nontoxic Small Molecule Inhibitors of Nek2 Kinase Using A Whole Animal-Based In Vivo Screening Approach
About forty thousand women die each year due to breast cancer occurrences in United States alone. Nek2 is a dimeric Ser/Thr protein kinase that localizes to centrosome and tightly regulates centrosome organization during the cell cycle. Any aberrant function of Nek2 leads to chromosome segregation error with cells containing abnormal chromosome contents - a condition known as Aneuploidy, an established cause of cancer. Recently published data revealed that the expression level of Nek2 kinase in invasive breast cancer (IBC) cell is abnormally high (3-5 fold), thereby suggesting that it may be directly involved in breast cancer transformation and possibly metastasis. Despite this, it remains unknown how exactly at the molecular level Nek2 transforms normal cells to malignant tumors. It also remains unclear if presence of excess Nek2 kinase in breast cancer cells plays any instrumental role in breast cancer metastasis. In addition, suitable chemical agents targeting Nek2 kinase with anti-cancer activity also remain absent. So far artificial cell-based system has been utilized to investigate the functional roles of Nek2 kinase in breast tumorigenesis, and in the inhibitor development process. Unfortunately, this has led to a limited clinical success thus far, since it is now known that the onset and progression of cancer often involves cooperation between multiple signaling pathways, and that a tissue-specific tumor microenvironment could play a critically important role in tumorigenesis.
An immediate goal of Kumar’s laboratory is to develop Nek2-based in vivo cancer models and utilize them to develop potent, selective, cell-active, and non-toxic Nek2 inhibitory agents. Subsequently, the developed Nek2 inhibitors will be utilized to dissect the undocumented function of Nek2 kinase in both normal cellular physiology and breast cancer progression. Click here to read more.