A5046877841- Synthesis and biological activity
- Microtubule and mitosis dynamics
- Synthesis and Biological Evaluation
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Protein Kinase Regulation and GTPase Signaling
- Synthesis of Indole Derivatives
- Melanoma and MAPK Pathways
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Prostate Cancer Treatment and Research
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Alzheimer's disease research and treatments
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and Characterization of Heterocyclic Compounds
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Cellular Mechanics and Interactions
- Viral Infectious Diseases and Gene Expression in Insects
- Peptidase Inhibition and Analysis
- Multicomponent Synthesis of Heterocycles
- Cell Adhesion Molecules Research
Purdue University West Lafayette
2016-2025
Center for Cancer Research
2016-2025
Banaras Hindu University
2012-2025
Purdue University Institute for Cancer Research
2009-2024
University of Michigan
2024
Scleroderma Foundation
2024
Kurnool Medical College
2023
Midas Multispeciality Hospital
2023
Gujarat Cancer Society
2023
University of North Carolina at Chapel Hill
2023
Protein phosphorylation plays a central role in controlling many diverse signal transduction pathways all cells. Novel protein kinases are identified at rapid rate using homology cloning methods and genetic screens or selections; however identification of the direct substrates has proven elusive to because tremendous redundancy overlapping substrate specificities among kinases. We describe development engineering-based method identify prototypical tyrosine kinase v-Src, which controls...
Epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are key underlying causes that promote extensive metastasis, drug resistance, tumor recurrence in highly lethal pancreatic cancer. The mechanisms leading to EMT CSC phenotypes not fully understood, which has hindered the development of effective targeted therapies capable improving treatment outcomes patients with cancer.We show a central role Aurora kinase A (AURKA) promoting via ALDH1A1, was discovered as its...
Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the conserved fold of catalytic domains. Through a combination small molecule synthesis and mutagenesis, potent (IC50 = 1.5 nM) uniquely specific inhibitor (4-amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-d]pyrimidine) rationally engineered v-Src tyrosine (Ile338Gly v-Src) has identified. Both potency specificity this compound surpass...
Abstract Oxidative stress is one of the earliest events in Alzheimer’s disease (AD). A chemical genetic screen revealed that deregulated cyclin‐dependent kinase 5 (Cdk5) may cause oxidative by compromising cellular anti‐oxidant defense system. Using novel Cdk5 modulators, we show mechanism which can induce disease’s early stage and cell death late stage. dysregulation upon neurotoxic insults results reactive oxygen species (ROS) accumulation neuronal cells because inactivation peroxiredoxin...
Aberrant activation of cell cycle proteins is believed to play a critical role in Alzheimer's disease (AD) pathogenesis; although, the molecular mechanisms leading their diseased neurons remain elusive. The goal this study investigate mechanistic link between Cdk5 deregulation and re-activation Aβ1-42-induced neurotoxicity. Using chemical genetic approach, we identified Cdc25A, Cdc25B, Cdc25C as direct substrates mouse brain lysates. We show that deregulated directly phosphorylates at...
We uncovered a crucial role for the Aurora kinase A (AURKA)-Twist1 axis in promoting epithelial-to-mesenchymal transition (EMT) and chemoresistance pancreatic cancer. Twist1 is first EMT-specific target of AURKA that was identified using an innovative screen. phosphorylates at three sites, which results its multifaceted regulation - inhibits ubiquitylation, increases transcriptional activity favors homodimerization. reciprocates prevents degradation, thereby triggering feedback loop....
Abstract Despite progress in prostate cancer (PC) therapeutics, distant metastasis remains a major cause of morbidity and mortality from PC. Thus, there is growing recognition that preventing or delaying PC holds great potential for substantially improving patient outcomes. Here we show receptor-interacting protein kinase 2 (RIPK2) clinically actionable target inhibiting metastasis. RIPK2 amplified/gained ~65% lethal metastatic castration-resistant Its overexpression associated with disease...
Modification of the ATP pocket on protein kinases allows selective use an analogue that exhibits high affinity for altered kinases. Using this approach, we ATP-binding site JNK and identifiedN 6-(2-phenythyl)-ATP, a modified form specificity modified, but not wild type form, JNK. its enables detection novel substrates. Among substrates identified using approach is heterogeneous nuclear ribonucleoprotein K, which involved in transcription post-transcriptional mRNA metabolism. The newly...