A5036506264- Monoclonal and Polyclonal Antibodies Research
- Amyotrophic Lateral Sclerosis Research
- Glycosylation and Glycoproteins Research
- Genetic Neurodegenerative Diseases
- Protein purification and stability
- Biochemical Acid Research Studies
- vaccines and immunoinformatics approaches
- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- Prostate Cancer Treatment and Research
- Cell Adhesion Molecules Research
- Nuclear Receptors and Signaling
- Advanced Proteomics Techniques and Applications
- RNA Research and Splicing
- Neurological disorders and treatments
- Microtubule and mitosis dynamics
- Pesticide Exposure and Toxicity
- Parkinson's Disease Mechanisms and Treatments
- Redox biology and oxidative stress
- T-cell and B-cell Immunology
- Prostate Cancer Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Microbial metabolism and enzyme function
Sanofi (France)
2024
University of Massachusetts Chan Medical School
2014-2024
Sanofi (United States)
2022-2023
Sanofi (Germany)
2020
University of Massachusetts Lowell
2009-2011
Florida State University
2010
The neonatal Fc receptor (FcRn) promotes antibody recycling through rescue from normal lysosomal degradation. binding interaction is pH-dependent with high affinity at low pH, but not under physiological pH conditions. Here, we combined rational design and saturation mutagenesis to generate novel variants prolonged half-life acceptable development profiles. First, a panel of point mutations was created 11 key FcRn-interacting sites on the region an antibody. Multiple slower FcRn dissociation...
Protein language models (PLMs) based on machine learning have demon-strated impressive success in predicting protein structure and function. However, general-purpose (“foundational”) PLMs limited performance antibodies due to the latter’s hypervariable regions, which do not conform evolutionary conservation principles that such rely on. In this study, we propose a new transfer framework called AbMAP, fine-tunes foundational for antibody-sequence inputs by supervising antibody binding...
Pathological alteration of TDP-43 (TAR DNA-binding protein-43), a protein involved in various RNA-mediated processes, is hallmark feature the neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Fragments TDP-43, composed second RNA recognition motif (RRM2) disordered C terminus, have been observed cytoplasmic inclusions sporadic cases, suggesting that conformational changes involving RRM2 together with terminus play role aggregation toxicity. The...
Incorporation of a reporter peptide in solutions submitted to fast photochemical oxidation proteins (FPOP) allows for the correction adventitious scavengers and enables normalization comparison time-dependent results. Reporters will also be useful differential experiments control inclusion radical-reactive species. This incorporation provides simple quick check radical dosage FPOP results from day-to-day lab-to-lab. Use workflow requires no additional measurements or spectrometers while...
Monoclonal antibodies (mAbs) are among the fastest growing and most effective therapies for myriad diseases. Multispecific an emerging class of novel therapeutics that can target more than one tumor- or immune-associated modulators per molecule. The combination different binding affinities classes, such as soluble membrane-bound antigens, within multispecific confers unique pharmacokinetic (PK) properties. Numerous factors affect antibody's PK, with affinity to neonatal Fc receptor (FcRn) a...
Abstract Folding intermediates mediate both protein folding and the misfolding aggregation observed in human diseases, including amyotrophic lateral sclerosis (ALS), are prime targets for therapeutic interventions. In this study, we identified core nucleus of structure a intermediate second RNA recognition motif (RRM2) ALS-linked RNA-binding protein, TDP-43, using combination experimental computational approaches. Urea equilibrium unfolding studies revealed that RRM2 state consists collapsed...
Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose “foundational” PLMs limited performance antibodies due to the latter’s hypervariable regions, which do not conform evolutionary conservation principles that such rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), fine-tunes foundational for antibody-sequence inputs by supervising on antibody structure and...
Misfolding of Cu, Zn superoxide dismutase (SOD1) variants may lead to protein aggregation and ultimately amyotrophic lateral sclerosis (ALS). The mechanism conformational changes during this process are complex remain unclear. To study SOD1 variant at the molecular level in solution, we chemically induced a mutant (G93A SOD1) with trifluoroethanol (TFE) used both native mass spectrometry (MS) analyze intact fast photochemical oxidation proteins (FPOP) characterize structural by TFE. We found...
Hybridoma technology has been valuable in the development of therapeutic antibodies. More recently, antigen-specific B-cell selection and display technologies are also gaining importance. A major limitation these approaches used for antibody discovery is extensive process cloning expression involved transitioning from identification to validating function, which compromises throughput discovery. In this study, we describe a identify rapidly re-format express antibodies functional...
Abstract Immunization based antibody discovery is plagued by the paucity of antigen-specific B cells. Identifying these cells akin to finding needle in a haystack. Current and emerging technologies while effective, are limited terms capturing repertoire. We report on bulk purification B-cells benefits it offers various platforms. Using five different antigens, we show hit rates 51–88%, compared about 5% with conventional methods. also that this highly efficient loss only 2% antigen specific...
Breast cancer is the second leading cause of cancerrelated deaths in women worldwide; a prime biomarker to aid diagnosis, directed treatment, clinical management, and reoccurrence this MUC1 peptide fragment: antigen 15-3 (CA 15-3). Herein, an immuno-fluorescence assay for CA was developed; ALYGNSA system consists protein biolinker (Protein G') adsorbed onto Poly (methyl methacrylate) (PMMA). The unique interaction Protein G' with PMMA, thermo-plastic polymer has been demonstrated improve...
HER-2/neu oncogene is over-expressed and amplified in patients associated with metastatic breast cancer. An increased level (>15 ng/mL) the shed extracellular domain (sECD-HER 2/neu) indicative of potential presence as-sociated progression this disease. A fluo-rescent ELISA incorporating newly devel-oped ALYGNSA antibody-orientation system revealed a 10-fold increase sensitivity (≤0.63 sECD-HER 2/neu when compared to control standard kit (≤7.5 ng/mL). This enhanced mode detection has not...
Abstract Parkinson’s disease and multiple system atrophy are members of a class devastating neurodegenerative diseases called synucleinopathies, which characterized by the presence alpha-synuclein (α-Syn) rich aggregates in brains patients. Passive immunotherapy targeting these is an attractive disease-modifying strategy. Such approach must not only demonstrate target selectivity towards α-Syn aggregates, but also achieve appropriate brain exposure to have desired therapeutic effect. Here we...
Pathological alteration of TDP-43 is a hallmark feature multiple neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Fragments, comprised the second RNA recognition motif (RRM2) disordered C-terminus, have been observed in cytoplasmic inclusions, suggesting that conformational changes within these regions play role aggregation toxicity. Circular dichroism fluorescence spectroscopies reveal three-state equilibrium unfolding model for RRM2...