A5071603739- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- RNA modifications and cancer
- RNA Research and Splicing
- HIV/AIDS drug development and treatment
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Sphingolipid Metabolism and Signaling
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- Blood Coagulation and Thrombosis Mechanisms
- Machine Learning in Bioinformatics
- Complement system in diseases
- Erythrocyte Function and Pathophysiology
- Advanced Proteomics Techniques and Applications
- Transgenic Plants and Applications
- Endoplasmic Reticulum Stress and Disease
- CAR-T cell therapy research
- Immune cells in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Fatty Acid Research and Health
- Atherosclerosis and Cardiovascular Diseases
Center for Biologics Evaluation and Research
2017-2022
United States Food and Drug Administration
2021-2022
Drexel University
2005-2017
Institute for Molecular Medicine
2005-2017
National Institute of Diabetes and Digestive and Kidney Diseases
2013-2017
National Institutes of Health
2013-2017
University of Massachusetts Amherst
2004
<ns4:p>Therapeutic protein drugs are an important class of medicines serving patients most in need novel therapies. Recently approved recombinant therapeutics have been developed to treat a wide variety clinical indications, including cancers, autoimmunity/inflammation, exposure infectious agents, and genetic disorders. The latest advances protein-engineering technologies allowed drug developers manufacturers fine-tune exploit desirable functional characteristics proteins interest while...
Due to the degeneracy of genetic code, most amino acids can be encoded by multiple synonymous codons. Synonymous codons naturally occur with different frequencies in organisms. The choice may affect protein expression, structure, and function. Recombinant gene technologies commonly take advantage former effect implementing a technique termed codon optimization, which are replaced ones order increase expression. This relies on accurate knowledge usage frequencies. Accurately quantifying bias...
Abstract As the SARS-CoV-2 pandemic is rapidly progressing, need for development of an effective vaccine critical. A promising approach to generate, through codon pair deoptimization, attenuated virus. This carries advantage that it only requires limited knowledge specific virus in question, other than its genome sequence. Therefore, well suited emerging viruses, which we may not have extensive data. We performed comprehensive silico analyses several features genomic sequence (e.g., usage,...
Abstract Synonymous codons occur with different frequencies in organisms, a phenomenon termed codon usage bias. Codon optimization, common term for variety of approaches used widely by the biopharmaceutical industry, involves synonymous substitutions to increase protein expression. It had long been presumed that variants, which, definition, do not alter primary amino acid sequence, have no effect on structure and function. However, critical mass reports suggests variations may impact...
Sphingolipid levels are tightly regulated to maintain cellular homeostasis. During pathologic conditions such as in aging, inflammation, and metabolic neurodegenerative diseases, of some sphingolipids, including the bioactive metabolite ceramide, elevated. metabolism has been linked autophagy, a critical catabolic process both normal cell function disease; however, vivo relevance interaction is not well-understood. Here, we show that blocking autophagy liver by deletion Atg7 gene, which...
The relationship between serine palmitoyltransferase (SPT) activity and ORMDL regulation of sphingolipid biosynthesis was investigated in mammalian HEK293 cells. Each the three human ORMDLs reduced increase long-chain base synthesis seen after overexpression wild-type SPT or containing C133W mutation hLCB1, which produces non-catabolizable sphingoid base, 1-deoxySa. ORMDL-dependent repression occurred whether expressed as individual subunits a heterotrimeric single-chain fusion protein....
Abstract Background HIV-1 gene expression is driven by the long terminal repeat (LTR), which contains many binding sites shown to interact with an array of host and viral factors. Selective pressures within as well low fidelity reverse transcriptase lead changes in relative prevalence genetic variants genome, including LTR, resulting quasispecies that can be differentially regulated potentially establish niches specific cell types tissues. Methods Utilizing flow cytometry electromobility...
Thrombosis is a recognized complication of Coronavirus disease 2019 (COVID-19) and often associated with poor prognosis. There well-recognized link between coagulation inflammation, however, the extent thrombotic events COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) Vitamin K epOxide Reductase Complex subunit (VKORC1), which are all proteins linked to coagulation, have been shown...
Coronavirus disease of 2019 (COVID-19) is the clinical manifestation respiratory infection caused by severe acute syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a disease, it clear that COVID-19 systemic illness impacting multiple organ systems. One defining feature has been high incidence thrombotic events. The underlying processes and risk factors for occurrence events in remain inadequately understood. bacterial, viral or fungal infections are well to activate...
As the SARS-CoV-2 pandemic is rapidly progressing, need for development of an effective vaccine critical. A promising approach to generate, through codon pair deoptimization, attenuated virus. This carries advantage that it only requires limited knowledge specific virus in question, other than its genome sequence. Therefore, well suited emerging viruses which we may not have extensive data. We performed comprehensive
Abstract Background Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage tissue-specific transcriptome. Cancer disrupts gene pattern healthy tissue resulting in altered preferences. The topic changes as they relate to demand, and tRNA supply cancer growing interest. Methods We analyzed transcriptome-weighted pair based on Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples 632 normal samples. This dataset represents 32 types...
Abstract Hemophilia B is a blood clotting disorder caused by deficient activity of coagulation factor IX (FIX). Multiple recombinant FIX proteins are currently approved to treat hemophilia B, and several gene therapy products being developed. Codon optimization frequently used technique in the pharmaceutical industry improve protein expression recoding coding sequence using multiple synonymous codon substitutions. The underlying assumption this that substitutions do not alter characteristics...
Over the past decade, advent of molecular techniques and deeper understanding tumor microenvironment (TME) have enabled development a multitude immunotherapy targets approaches. Despite revolutionary advancement in immunotherapy, treatment resistance remains challenge leading to decreased response rate significant proportion patients. As such, there has recently been an evolving focus enhance efficacy, durability, toxicity profiles immunotherapy. Although immune checkpoint inhibitors...
Cells of the monocyte–macrophage lineage play an important role in human immunodeficiency virus type 1 (HIV-1)-associated disease. Infected myeloid precursor cells bone marrow are thought to be a viral reservoir that may repopulate peripheral blood, central nervous system (CNS), and other organ systems throughout course To model select aspects HIV-1 infection compartment vitro, erythro-myeloid cell line, TF-1, was used. Phorbol 12-myristate 13-acetate (PMA) found induce TF-1 line...
Abstract Human T cell leukemia virus type 1 (HTLV-1) has previously been shown to infect antigen-presenting cells and their precursors in vivo. However, the role these important populations play pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis or adult remains unresolved. To better understand how HTLV-1 infection may potentially impact disease progression, regulation viral gene expression established monocytic lines was examined. U-937 promonocytic transiently...
Approximately one-third of the AIDS cases in United States have been attributed to use injected drugs, frequently involving abuse opioids. Consequently, it is critical address whether opioid directly contributes altered susceptibility HIV-1 beyond increased risk exposure. Previous vitro and vivo studies addressing role μ-opioid agonists altering levels co-receptor CXCR4 subsequent replication yielded contrasting results. The bone marrow believed be a potential anatomical sanctuary for HIV-1....