A5036456864- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- Advanced Biosensing Techniques and Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Library Science and Information Systems
- Cancer-related gene regulation
- Mosquito-borne diseases and control
- Insect symbiosis and bacterial influences
- Machine Learning in Materials Science
- Histone Deacetylase Inhibitors Research
- Lymphoma Diagnosis and Treatment
- Viral Infections and Vectors
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Computational Drug Discovery Methods
University of Florida
2022-2024
Scripps Research Institute
2018-2023
Jupiter Medical Center
2023
National Center for Advancing Translational Sciences
2018
National Institutes of Health
2018
AbbVie (United States)
2017
Abstract Assessment of the interactions between a drug and its protein target in physiologically relevant cellular environment constitutes major challenge pre-clinical discovery space. The Cellular Thermal Shift Assay (CETSA) enables such an assessment by quantifying changes thermal stability proteins upon ligand binding intact cells. Here, we present development validation homogeneous, standardized, target-independent, high-throughput (384- 1536-well formats) CETSA platform that uses split...
The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in American continent poses a major health hazard for unborn fetuses pregnant women. To date, there is no effective medical intervention. nonstructural protein 5 (ZIKV-NS5) critical ZIKV replication through 5′-RNA capping and RNA polymerase activities present its N-terminal methyltransferase (MTase) C-terminal RNA-dependent (RdRp) domains, respectively. crystal structure full-length ZIKV-NS5 has been...
The active sites of hundreds human α-ketoglutarate (αKG) and Fe(II)-dependent dioxygenases are exceedingly well preserved, which challenges the design selective inhibitors. We identified a noncatalytic cysteine (Cys481 in KDM5A) near KDM5 histone H3 lysine 4 demethylases, is absent other demethylase families, that could be explored for interaction with cysteine-reactive electrophile acrylamide. synthesized analogs thienopyridine-based inhibitor chemotype, namely,...
Abstract Although the 5-year survival rate of chronic lymphocytic leukemia (CLL) patients has risen to >80%, only potentially curative treatment is allogeneic hematopoietic stem cell transplantation (alloHSCT). To identify possible new monoclonal antibody (mAb) drugs and targets for CLL, we previously developed a phage display–based human mAb platform mine repertoire who responded alloHSCT. We had selected group highly homologous post-alloHSCT mAbs that bound an unknown CLL surface...
Despite numerous therapeutic options, safe and curative therapy is unavailable for most patients with chronic lymphocytic leukemia (CLL). A drawback of current therapies such as the anti-CD20 monoclonal antibody (mAb) rituximab elimination all healthy B cells, resulting in impaired humoral immunity. We previously reported identification a patient-derived, CLL-binding mAb, JML-1, identified sialic acid-binding immunoglobulin-like lectin-6 (Siglec-6) target JML-1. Although little known about...
Abstract Siglec-6 is a lectin receptor with restricted expression in the placenta, mast cells and memory B-cells. Although expressed patients chronic lymphocytic leukemia (CLL), its pathophysiological role has not been elucidated. We describe here for migration adhesion of CLL B to CLL- bone marrow stromal (BMSCs) vitro compromised spleen vivo. Mass spectrometry analysis revealed interaction DOCK8, guanine nucleotide exchange factor. Stimulation MEC1-002 ligand, sTn, results Cdc42...
The antigen-binding fragment (Fab) is the ∼50-kDa monovalent arm of an antibody molecule. In laboratory, Fab can be produced via either enzymatic digestion or recombinant expression, and its use facilitates accurate assessment affinity specificity monoclonal antibodies. high melting temperature Fab, together with low tendency to aggregate ready conversion natural nonnatural immunoglobulin (Ig) formats (without affecting antigen binding properties), have made it a preferred format for phage...
Abstract Objectives of the Study: Bispecific antibodies (BsAbs) are a class immunotherapy drugs that facilitate targeted killing cancer cells. Here, we report therapeutic potential novel Siglec-6/CD3 bsAb against chronic lymphocytic leukemia (CLL) We show here for first time functional and relevance Siglec-6 in CLL cell adhesion migration. Mechanistically, have shown mediated migration through ligand (sialyl Tn) DOCK8 dependent activation Cdc42 associated with actin polymerization. To...