A5058987536- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Alzheimer's disease research and treatments
- Protein Kinase Regulation and GTPase Signaling
- Microbial metabolism and enzyme function
- Mass Spectrometry Techniques and Applications
- Protein Tyrosine Phosphatases
- Trace Elements in Health
- Porphyrin Metabolism and Disorders
- Cell death mechanisms and regulation
- Primary Care and Health Outcomes
- Enzyme Structure and Function
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Protein Degradation and Inhibitors
- Cholinesterase and Neurodegenerative Diseases
- Histone Deacetylase Inhibitors Research
- Metal-Catalyzed Oxygenation Mechanisms
- HER2/EGFR in Cancer Research
- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- COVID-19 and healthcare impacts
- Healthcare Policy and Management
University of Michigan
2010-2022
Georgetown University
2020
The discovery of activation state dependent kinase inhibitors, which bind specifically to the inactive conformation protein, is considered be a promising pathway improved cancer treatments. Identifying such inhibitors challenging, however, because they can have Kd values similar molecules known inhibit function by interacting with active form. Further, while inhibitor induced changes within tertiary structure are significant, few technologies able correctly assign binding modes in...
On the basis of synergism observed between a selective c-Src kinase inhibitor with an HDAC inhibitor, development first chimeric and is described. The optimized shown to be potent inhibitor. Chimeric 4 further highly efficacious in cancer cell lines significantly more than dual-targeting strategy using discrete inhibitors.
Alzheimer′s disease (AD) is a multifactorial neurodegenerative related to the deposition of aggregated amyloid‐ β (A ) peptides in brain. It has been proposed that metal ion dyshomeostasis and miscompartmentalization contribute AD progression, especially as ions (e.g., Cu(II) Zn(II)) found A plaques diseased brain can bind be linked aggregation neurotoxicity. The role pathogenesis, however, uncertain. To accelerate understanding this area therapeutic development, recent efforts devise...
The design of multifunctional, neuroprotective compounds has received increasing attention due to their perceived utility in targeting not only the diverse comorbidity neurological disorders, but also typically complex pathoetiological pathways leading these including insoluble proteins associated with many human neurodegenerative diseases aging and radical-generating enzyme actions brain. For this purpose, herein, we present inhibitory studies on monoamine oxidase (MAO) a chemical library...
Protein kinase pathways are traditionally mapped by monitoring downstream phosphorylation. Meanwhile, the noncatalytic functions of protein kinases remain under-appreciated as critical components signaling. c-Src is a known to have signaling function important in healthy and disease cell Large conformational changes regulatory domains regulate c-Src's functions. Herein, we demonstrate that global conformation can be monitored using selective proteolysis methodology. Further, use this...
Lon and ClpXP are the only soluble ATP-dependent proteases within mammalian mitochondria matrix, which function in protein quality control by selectively degrading misfolded, misassembled, or damaged proteins. Chemical tools to study these biological samples have not been identified, thereby hindering a clear understanding of their respective functions normal disease states. In this study, we applied proteolytic site-directed approach identify peptide reporter substrate inhibitor that...
Small molecule kinase inhibitors have shown immense clinical utility for diverse indications. While >60 been approved (and many more in trials), it remains unclear whether the efficacy of a inhibitor is solely dependent on enzymatic inhibition, or non-catalytic functions play role some inhibitors. Here, we designed and synthesized series pyrazolopyrimidine that modulate global conformation c-Src kinase. Expanding upon our findings from series, designed, synthesized, evaluated three pair...
Abstract The United States Coronavirus Aid, Relief, and Economic Security Act (CARES Act) led to creation of the Paycheck Protection Program, as well an expansion reimbursements for telemedicine. CARES drafters over emphasized maintaining employment overlooked negative downstream effects policies had on outpatient clinics. misalignment between this financial aid package public health policy is most apparent in pressure administrators face maintain clinic operations, without a transition plan...