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. The current research projects include the development of small molecule probes (e.g. inhibitors and biosensors) of cysteine cathepsins, protein kinases, and protein tyrosine phosphatases - critically important group of cellular signaling enzymes, implicated in several human diseases. The developed probes are subsequently utilized to understand the enzyme function in both normal cellular physiology and human diseases. 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 and assay development, mass spectrometric analysis, inhibitor screening, development of in vivo animal model for therapeutic development, and structure-based ligand design.
About forty thousand women die each year due to breast cancer occurrences in the United States alone. Nek2 is a dimeric Ser/Thr protein kinase that localizes to centrosomes and tightly regulates centrosome organization during the cell cycle. Recently published data reveals that the expression level of Nek2 kinase in the invasive breast cancer (IBC) cell is abnormally high (3-5 fold). 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 overabundant Nek2 plays any important role in breast cancer metastasis. In addition, suitable inhibitory agents targeting Nek2 kinase with anti-cancer activity also remain scarcely available. Until now, to probe the potential role of Nek2 kinase in cancer, and during the inhibitor development process, only artificial cell-based system has been utilized. Unfortunately, this has led to a limited clinical success so far, since the onset and progression of cancer often involves a cooperation between multiple signaling pathways. An immediate goal of Kumar’s laboratory is to develop Nek2-based in vivo models in Drosophila melanogaster and utilized them during the development of Nek2-targeting anti-cancer agents. An activity-based small molecule biosensor of Nek2 kinase is also under development. The developed inhibitor, biosensor, and the whole animal models will be utilized to dissect the undocumented function of Nek2 kinase in both normal cellular physiology and breast cancer progression. This work is currently in progress in collaborations with the laboratory of Prof. Ross L. Cagan's (Mount Sinai School of Medicine), and Prof. Tanaji T. Talele (St. Johns University).
Development of Covalent and Irreversible Inhibitors of Protein Tyrosine Phosphatases for Functional Proteomics
Protein tyrosine phosphorylation is a dominant post-translational modification that is extensively utilized by the mammalian cellular machinery to carry out many important biological processes, such as cell differentiation, cell proliferation, cell growth, cell survival, vesicular trafficking, cell migration, and cell-cell communication. This simple, yet target-specific, modification is carried out by a relatively large family of signaling enzymes known as protein tyrosine phosphatases (PTPs). Not surprisingly, any faulty actions of PTPs have been directly linked to a variety of human diseases, such as human cancer, diabetes, and autoimmune disorders. Given their relevance in the pathology of numerous human diseases, it is perhaps not surprising that selective inhibitory interception of many PTP members (e.g. PTP1B, SHP2, Cdc25, and PRL phosphatases) is desired for therapeutic developments. Despite this, the intracellular biology of individual PTP members in both normal and diseased cells remains largely unexplored. This is mainly due to the paucity of suitable chemical tools needed to dissect their functional significance. Click here to learn more about other projects in Kumar's laboratory.