James E. Melnyk
A5046273752- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Prostate Cancer Treatment and Research
- Antimicrobial Peptides and Activities
- Gut microbiota and health
- Computational Drug Discovery Methods
- vaccines and immunoinformatics approaches
- Pediatric health and respiratory diseases
- Inflammatory Bowel Disease
- Estrogen and related hormone effects
- Influenza Virus Research Studies
- Hormonal and reproductive studies
- Cancer, Lipids, and Metabolism
- Hepatitis B Virus Studies
- Inflammasome and immune disorders
- COVID-19 Clinical Research Studies
- Clostridium difficile and Clostridium perfringens research
- Advanced Proteomics Techniques and Applications
- Viral Infections and Outbreaks Research
- Heat shock proteins research
- Bacterial Genetics and Biotechnology
- Antimicrobial Resistance in Staphylococcus
- IL-33, ST2, and ILC Pathways
- Cancer Research and Treatments
- Mycobacterium research and diagnosis
University of California, San Francisco
2020-2023
City College of San Francisco
2023
Howard Hughes Medical Institute
2020-2021
Quantitative BioSciences
2020-2021
University of Delaware
2012-2017
A newly described coronavirus named severe acute respiratory syndrome 2 (SARS-CoV-2), which is the causative agent of disease 2019 (COVID-19), has infected over 2.3 million people, led to death more than 160,000 individuals and caused worldwide social economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for treatment COVID-19, nor there any vaccines that prevent infection SARS-CoV-2, efforts develop hampered by limited knowledge molecular details how SARS-CoV-2...
ABSTRACT An outbreak of the novel coronavirus SARS-CoV-2, causative agent COVID-19 respiratory disease, has infected over 290,000 people since end 2019, killed 12,000, and caused worldwide social economic disruption 1,2 . There are currently no antiviral drugs with proven efficacy nor there vaccines for its prevention. Unfortunately, scientific community little knowledge molecular details SARS-CoV-2 infection. To illuminate this, we cloned, tagged expressed 26 29 viral proteins in human...
Mammalian Nod2 is an intracellular protein that implicated in the innate immune response to bacterial cell wall and associated with development of Crohn’s disease, Blau syndrome, gastrointestinal cancers. required for muramyl dipeptide (MDP), immunostimulatory fragment wall, but it not known whether MDP binds directly Nod2. We report expression purification human from insect cells. Using novel self-assembled monolayers (SAMs), we provide first biochemical evidence a direct, high-affinity...
Abstract Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic protein abundance analyses using three strains (pH1N1, H3N2, H5N1) in human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions 13 IAV-modulated kinases....
Natural modifications of peptidoglycan modulate the innate immune response. Peptidoglycan derivatives activate this response via intracellular receptor, Nod2. To probe how these alter response, a novel and efficient carbohydrate synthesis was developed to allow for late-stage modification amine at 2-position. Modification found be important stabilizing Nod2 generating proper The native ligands demonstrate significant increase in cellular stability Moreover, changing identity natural...
Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide and massive societal economic burden. Recently, a new variant SARS-CoV-2, known as B.1.1.7, was first detected the United Kingdom is spreading several other countries, heightening public health concern raising questions to resulting effectiveness vaccines therapeutic interventions. We others previously identified host-directed...
The human gut must regulate its immune response to resident and pathogenic bacteria, numbering in the trillions. peptidoglycan component of bacterial cell wall is a dense rigid structure that consists polymeric carbohydrates highly cross-linked peptides which offers protection from host surrounding environment. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), membrane-associated innate receptor found epithelium mutated an estimated 30% Crohn's disease patients, binds...
Alternative splicing of the androgen receptor (AR) is frequently observed in castration resistant prostate cancer (CRPC). One AR isoform, AR-V7 splice variant, a constitutively active transcription factor which lacks ligand binding domain and therefore undruggable. expression correlates with resistance to signaling inhibitors (ARSi) poor clinical prognoses. The occurrence variant driven by alternative pre-mRNA spliceosome, however mechanistic details are poorly understood. We demonstrate...
Abstract The androgen receptor (AR) is a central driver of aggressive prostate cancer. After initial treatment with signaling inhibitors (ARSi), reactivation AR leads to resistance. Alternative splicing mRNA yields the AR-V7 splice variant, which currently an undruggable mechanism ARSi resistance: lacks ligand binding domain, where hormones and anti-androgen antagonists act, but still activates signaling. We reveal PKCβ as druggable regulator transcription at genomic locus. identify clinical...
Nod2 is a cytosolic, innate immune receptor responsible for binding to bacterial cell wall fragments such as muramyl dipeptide (MDP). Upon binding, subsequent downstream activation of the NF-κB pathway leads an response. mutations are correlated with increased susceptibility Crohn's disease (CD) and ultimately result in misregulated Previous work had demonstrated that interacts stabilized by molecular chaperone Hsp70. In this work, it shown using purified protein vitro biochemical assays...
The innate immune system is the body’s first line of defense against pathogens. triggered by pathogen associated molecular patterns (PAMPs) that are recognized pattern recognition receptors (PRRs) such as Toll‐like (TLRs) and Nod‐like (NLRs). This research project focuses on providing a better understanding how senses responds to presence bacteria. Specifically, our group interested in relationship between Nucleotide‐binding oligomerization domain‐containing protein 2 (Nod2), an NLR found...
Chronic inflammatory disorders, such as Inflammatory Bowel Disease, arise from an inappropriate immune response to bacteria. In order treat these diseases, we need a better understanding of how the innate system senses and responds It has long been known that muramyl dipeptide (MDP,Figure 1), fragment bacterial cell wall (peptidoglycan), is able generate response. Recently, it shown intracellular, mammalian protein Nod2 involved in sensing presence MDP cell, leading activation synthesis...
The objective of this study is to determine the activity and binding capabilities Crohn's associated mutant Nod2 protein. disease a debilitating inflammatory bowel alleged be caused by genetic factors malfunctioning immune system. A susceptibility gene has been identified on chromosome 16 that responsible for encoding nucleotide‐binding oligomerization domain‐containing protein 2 (Nod2). an innate receptor responds bacterial cell wall fragments initiate NF‐κB pathway. Three specific...
Every organism, from the complex to single cellular, is surrounded by trillions of microorganisms. In order survive an organism must be able recognize and adapt microbiome that surrounds it. The ability these microorganisms occurs when appropriate pathogen associated molecular pattern (PAMPs) binds proper recognition receptor (PRR). PAMPs are molecules associate with such as lipopolysaccharide, viral RNA, peptidoglycan. Interestingly, yeast respond small generated bacteria. Recognition...
During a bacterial infection, the body's first line of defense is provided by innate immune system. This system triggered pathogen‐associated molecular patterns (PAMPs) that are recognized different members called pattern recognition receptors (PRRs). One such PRR interest nucleotide‐binding oligomerization domain‐containing protein 2 (Nod2). Mammalian Nod2 cytosolic binds to and signals in response carbohydrate containing cell wall fragments; smallest which muramyl dipeptide (MDP)....
Abstract BACKGROUND The androgen receptor (AR) is the central therapeutic target in advanced prostate cancer (PCa). While treatments that directly AR are effective prolonging patient survival, aggressive cancers invariably find a way to evade these therapies. Frequently, evasion mechanisms reestablish expression and therefore AR-driven oncogenic pathways restored. Comprehensively understanding protein regulation machinery of identifying alternative targets crucial for treatment this disease....