A5048419154- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Protein Structure and Dynamics
- Immunotherapy and Immune Responses
- Transgenic Plants and Applications
- Biochemical and Structural Characterization
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Protein purification and stability
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Cancer Immunotherapy and Biomarkers
- IoT and Edge/Fog Computing
- Photoreceptor and optogenetics research
- Chemical Synthesis and Analysis
- Retinal Development and Disorders
- Cell Image Analysis Techniques
- Viral Infections and Outbreaks Research
- Chromosomal and Genetic Variations
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Photochromic and Fluorescence Chemistry
Chonnam National University
2021-2025
Chonnam National University Hwasun Hospital
2020-2024
Chonnam National University Hospital
2024
Dartmouth College
2013-2020
Korea Advanced Institute of Science and Technology
2017-2020
Seoul National University
2020
Dartmouth Hospital
2014-2015
Hanover College
2015
University of Oxford
2009-2013
Abstract Loops are the most variable regions of protein structure and are, in general, least accurately predicted. Their prediction has been approached two ways, ab initio database search. In recent years, it thought that methods more powerful. light continued rapid expansion number known structures, we have re‐evaluated FREAD, a search method demonstrate power may underestimated. We found sequence similarity as quantified by environment specific substitution scores can be used to...
Antibodies derived from non-human sources must be modified for therapeutic use so as to mitigate undesirable immune responses. While complementarity-determining region (CDR) grafting-based humanization techniques have been successfully applied in many cases, it remains challenging maintain the desired stability and antigen binding affinity upon grafting. We developed an alternative approach called CoDAH ("Computationally-Driven Antibody Humanization") which computational protein design...
Therapeutic proteins continue to yield revolutionary new treatments for a growing spectrum of human disease, but the development these powerful drugs requires solving unique set challenges. For instance, it is increasingly apparent that mitigating potential anti-therapeutic immune responses, driven by molecular recognition therapeutic protein's peptide fragments, may be best accomplished early in drug process. One eliminate immunogenic fragments mutating cognate amino acid sequences,...
Heart failure is a leading cause of death and often accompanied by activation quiescent cardiac myofibroblasts, which results in fibrosis. In this study, we aimed to identify novel circular RNAs that regulate We applied transverse aortic constriction (TAC) for 1, 4, 8 weeks mice. RNA sequencing datasets were obtained from fibroblasts isolated use Langendorff apparatus then further processed selection criteria such as differential expression conservation species. CircSMAD4 was upregulated TAC...
Understanding where antibodies recognize antigens can help define mechanisms of action and provide insights into progression immune responses. We investigate the extent to which information about binding specificity implicitly encoded in amino acid sequence be leveraged identify antibody epitopes. In computationally-driven epitope localization, possible antibody–antigen modes are modeled, targeted panels antigen variants designed experimentally test these hypotheses. Prospective application...
Abstract Flagellin, a protein-based Toll-like receptor agonist, is versatile adjuvant applicable to wide spectrum of vaccines and immunotherapies. Given reiterated treatments immunogenic biopharmaceuticals should lead antibody responses precluding repeated administration, the development flagellin not inducing specific antibodies would greatly expand chances clinical applications. Here we computationally identified regions in Vibrio vulnificus B deimmunized by simply removing cell epitope...
Abstract Neoantigens are ideal targets for cancer immunotherapy because they expressed de novo in tumor tissue but not healthy and therefore recognized as foreign by the immune system. Advances next-generation sequencing bioinformatics technologies have enabled quick identification prediction of tumor-specific neoantigens; however, only a small fraction predicted neoantigens immunogenic. To improve predictability immunogenic neoantigens, we developed silico neoantigen workflows VACINUS pMHC...
Protein nanocages are multimeric structures that can be engineered to mimic the molecular conformation of microorganisms. Based on previous findings showing a mucosal FlaB-tPspA fusion (flagellin fused with truncated PspA antigen Streptococcus pneumoniae) vaccine-induced protective immune response against S. pneumoniae, we develop ferritin nanocage vaccine displaying multivalent presentation both and adjuvant nanocarrier using SpyTag/SpyCatcher strategy. The 1:1 antigen/adjuvant is further...
Antibodies are used extensively in medical and biological research. Their complementarity determining regions (CDRs) define the majority of their antigen binding functionality. CDR structures have been intensively studied classified (canonical structures). Here we show that structure prediction is no different from standard loop problem predict them without classification. FREAD, a successful database technique, able to produce accurate predictions for all loops (0.81, 0.42, 0.96, 0.98, 0.88...
Staphylococcus aureus infections exert a tremendous burden on the health-care system, and threat of drug-resistant strains continues to grow. The bacteriolytic enzyme lysostaphin is potent antistaphylococcal agent with proven efficacy against both drug-sensitive strains; however, enzyme's own bacterial origins cause undesirable immunogenicity pose barrier clinical translation. Here, we deimmunized using computationally guided process that optimizes sets mutations delete immunogenic T cell...
ABSTRACT Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems enzyme suffer from various limitations, and there remains need an efficient cost-effective production process to facilitate clinical translation development nonmedical applications. While Pichia pastoris is widely used high-level recombinant proteins, are two major...
L-Asparaginase (L-ASNase), a bacterial enzyme that degrades asparagine, has been commonly used in combination with several chemical drugs to treat malignant hematopoietic cancers such as acute lymphoblastic leukemia (ALL). In contrast, the was known inhibit growth of solid tumor cells vitro, but not be effective vivo. We previously reported two novel monobodies (CRT3 and CRT4) bound specifically calreticulin (CRT) exposed on tissues during immunogenic cell death (ICD). Here, we engineered...
Anti-drug immune responses are a unique risk factor for biotherapeutics, and undesired immunogenicity can alter pharmacokinetics, compromise drug efficacy, in some cases even threaten patient safety. To fully capitalize on the promise of more efficient generally applicable protein deimmunization tools needed. Mutagenic deletion protein's T cell epitopes is one powerful strategy to engineer immunotolerance, but deimmunizing mutations must maintain structure function. Here, EpiSweep,...
The identification of T-cell epitopes has many profound translational applications in the areas transplantation, disease diagnosis, vaccine/therapeutic protein development and personalized immunotherapy. While data-driven methods have been widely used for prediction peptide binders with notable successes, structural modeling binding to MHC molecules is crucial understanding underlying molecular mechanism immunological processes.We developed GradDock, a structure-based method rapid accurate...
Loops are irregular structures which connect two secondary structure elements in proteins. They often play important roles function, including enzyme reactions and ligand binding. Despite their importance, remains difficult to predict. Most protein loop prediction methods sample local segments score them. In particular classifications database search depend heavily on properties of loops. Here we examine the distance between a loop's end points (span). We find that distribution span appears...
The immunogenicity of biotherapeutics can bottleneck development pipelines and poses a barrier to widespread clinical application. As result, there is growing need for improved deimmunization technologies. We have recently described algorithms that simultaneously optimize proteins both reduced T cell epitope content high-level function. In silico analysis this dual objective design space reveals no single global optimum with respect protein deimmunization. Instead, mutagenic deletion yields...
Abstract The protein universe displays a wealth of therapeutically relevant activities, but T‐cell driven immune responses to non‐“self” biological agents present major impediment harnessing the full diversity these molecular functions. Mutagenic epitope deletion seeks mitigate response, can typically address only small number epitopes. Here, we pursue “bottom‐up” approach that redesigns an entire remain native‐like contain few if any immunogenic We do so by extending Rosetta...
Protein binders including antibodies are known not to bind random sites of target proteins, and their functional effectiveness mainly depends on the binding region, called epitope. For development protein with desired functions, it is thus critical understand which surface region prefer (or do prefer) bind. The current methods for epitope prediction focus static indicators such as structural geometry or amino acid propensity, whereas events in fact a consequence dynamic interactions. Here,...
Small GTPases are key signaling nodes that regulate the cellular processes and subcellular events, their abnormal activities dysregulations closely linked with diverse cancers. Here, we report development of conformation-selective protein binders for a KRAS mutant. The conformation-specific were selected from repebody scaffold composed LRR (Leucine-rich repeat) modules through phage display modular engineering against constitute active conformation KRAS. Epitope was mapped to be located...
Humanization reduces the immunogenicity risk of therapeutic antibodies non-human origin. Thermostabilization can be critical for clinical development and application antibodies. Here, we show that computational antibody redesign method Computationally Driven Antibody (CoDAH) enables these two goals to accomplished simultaneously seamlessly. A panel CoDAH designs murine parent cetuximab, a chimeric anti-EGFR antibody, exhibited both substantially improved thermostabilities higher levels...