- Advanced Proteomics Techniques and Applications
- Parkinson's Disease Mechanisms and Treatments
- Mass Spectrometry Techniques and Applications
- Peptidase Inhibition and Analysis
- Biosimilars and Bioanalytical Methods
- Advanced Neuroimaging Techniques and Applications
- Advanced NMR Techniques and Applications
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Electron Spin Resonance Studies
- Heavy Metal Exposure and Toxicity
- RNA modifications and cancer
- Cytomegalovirus and herpesvirus research
- Phagocytosis and Immune Regulation
- Genetic Neurodegenerative Diseases
- Digital Communication and Language
- Health, Environment, Cognitive Aging
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related gene regulation
- Metabolomics and Mass Spectrometry Studies
- Signaling Pathways in Disease
- Chemical Reactions and Isotopes
- Protein Degradation and Inhibitors
- Ginkgo biloba and Cashew Applications
- Advanced Biosensing Techniques and Applications
AbbVie (United States)
2023
Northwestern University
2017-2022
University of Wisconsin–Madison
2011-2014
University of Illinois Urbana-Champaign
2007-2011
α-Synuclein (AS) is an intrinsically unstructured protein in aqueous solution but capable of forming β-sheet-rich fibrils that accumulate as intracytoplasmic inclusions Parkinson disease and certain other neurological disorders. However, AS binding to phospholipid membranes leads a distinct change conformation, stabilizing extended amphipathic α-helical domain reminiscent the exchangeable apolipoproteins. To better understand significance this conformational change, we devised novel...
The carboxyl groups of tryptic peptides were derivatized with a tertiary or quaternary amine labeling reagent to generate more highly charged peptide ions that fragment efficiently by electron transfer dissociation (ETD). All groups-aspartic and glutamic acid side-chains as well C-termini-were an average reaction efficiency 99 %. This nearly complete avoids making complex mixtures even because partially-labeled products, it allows the use static modifications during database searching. Alkyl...
Protein aggregation is implicated in the etiology of numerous neurodegenerative diseases. An understanding mechanisms enhanced by atomic-resolution structural information, which relatively little currently available. Lewy bodies, pathological hallmark Parkinson's disease, contain large quantities fibrillar α-synuclein (AS). Here we present solid-state NMR spectroscopy studies dried AS fibrils. The spectra have high resolution and sensitivity, site-resolved chemical shifts agree very well...
Quantification of gas-phase intact protein ions by mass spectrometry (MS) is impeded highly-variable ionization, ion transmission, and detection efficiencies. Therefore, quantification proteins using MS-associated techniques almost exclusively done after proteolysis where peptides serve as proxies for estimating abundance. Advances in instrumentation, separations, informatics have made large-scale sequencing top-down proteomics accessible to the community; yet a workflow has largely been...
Direct mass spectrometric quantification of peptides and proteins is compromised by the wide variabilities in ionization efficiency which are hallmarks both MALDI ESI techniques. We describe here implementation a fluorescence detection system for measurement UV-excited intrinsic (UV-IF) from just prior to their exit electrospray an capillary. The signal provides quantifiable measure amount protein or peptide present, while direct tandem analysis (MS/MS) on ESI-generated ions information...
Endosulfine-α (ENSA) is a 121-residue cAMP-regulated phosphoprotein, originally identified as an endogenous regulator of ATP-sensitive potassium channels. ENSA has been implicated in the regulation insulin secretion, and expression decreased brains both Alzheimer's disease (AD) Down's syndrome patients. We recently described membrane-dependent interactions between Parkinson's associated protein α-synuclein. Here we characterize conformational change that occurs upon binding to membranes....
We present an ultra-sensitive, minimally-invasive method for quantifying cotinine in dried blood spot (DBS) samples as a biomarker of exposure to tobacco smoke that can be collected using simple heel or finger prick obtain samples.Cotinine levels were measured matched plasma and reconstituted DBS from smokers nonsmokers evaluate assay parameters. In addition, we applied this new finger-prick infants, children young adults ages 1-21 estimate smoke. Partitioning across red cells haematocrit...
Antibody-drug conjugates (ADC) have gained momentum for treatment of cancers, with 14 ADCs currently approved commercial use worldwide. Calicheamicin is one the payloads contributing to this trend, being used both gemtuzumab ozogamicin (GO; trade name: Mylotarg) and inotuzumab (IO; Besponsa). Here we discuss catabolic pathway metabolism ABBV-011, a novel SEZ6-targeted, calicheamicin-based ADC investigated small cell lung cancer (SCLC). Specifically, our investigation has found that disulfide...