Costel Darie

Clarkson University · Department of Chemistry & Biomolecular Science, Biochemistry & Proteomics Group

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects approximately 1/68 children, with a more recent study suggesting numbers as high as 1/36. According to Diagnostic and Statistical Manual of Mental Disorders, the etiology of ASD is unknown and diagnosis of this disorder is behavioral. There is currently no biomarker signat...

Breast cancer (BC) is characterized by an extensive genotypic and phenotypic heterogeneity. In-depth investigations into the molecular bases of BC phenotypes, carcinogenesis, progression, and metastasis are necessary for accurate diagnoses, prognoses, and therapy assessments in predictive, precision, and personalized oncology. This review discusses...

Invasive ductal carcinoma (IDC) is the most common histological subtype of malignant breast cancer (BC), and accounts for 70–80% of all invasive BCs. IDC demonstrates great heterogeneity in clinical and histopathological characteristics, prognoses, treatment strategies, gene expressions, and proteomic profiles. Significant proteomic determinants of...

Breast Cancer (BC) is one of the most common cancers and one of the most common causes for cancer- related mortality. Discovery of protein biomarkers associated with cancer, is considered as important for early diagnosis and prediction of the cancer risk. Protein biomarkers could be investigated by large-scale protein investigation or proteomics, u...

Amyotrophic lateral sclerosis (ALS) consists of the progressive degeneration of motor neurons, caused by poorly understood mechanisms for which there is no cure. Some of the cellular perturbations associated with ALS can be detected in peripheral cells, including lymphocytes from blood. A related cell system that is very suitable for research consi...

Lung squamous cell carcinoma (LSCC) has a high mutational burden and poor prognosis, even with immunotherapy. In the Lux-Lung 8 trial, afatinib, an epidermal growth factor receptor (EGFR) inhibitor, showed a long-term benefit in 5.3% of patients with LSCC. Because activating mutations of EGFR are rare in LSCC, the response was likely due to wild-ty...

Per- and polyfluoroalkyl substances (PFAS) are a diverse family of industrially significant synthetic chemicals infamous for extreme environmental persistence and global environmental distribution. Many PFAS are bioaccumulative and biologically active mainly due to their tendency to bind with various proteins. These protein interactions may be the...

The electrochemically controlled release of proteins was studied in a Ca2+-cross-linked alginate hydrogel deposited on an electrode surface. The electrochemical oxidation of ascorbate or reduction of O2 was achieved upon applying electrical potentials +0.6 or -0.8 V (vs Ag/AgCl/KCl 3 M), respectively, resulting in decreasing or increasing pH locall...

Human jumping translocation breakpoint (hJTB) gene is located on chromosome 1q21 and is involved in unbalanced translocation in many types of cancer. JTB protein is ubiquitously present in normal cells but it is found to be overexpressed or downregulated in various types of cancer cells, where this protein and its isoforms promote mitochondrial dys...

It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of...

Immunohistochemistry (IHC) is still widely used as a morphology-based assay for in situ analysis of target proteins as specific tumor antigens. However, as a very heterogeneous collection of neoplastic diseases, breast cancer (BC) requires an accurate identification and characterization of larger panels of candidate biomarkers, beyond ER, PR, and H...

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is one of the most widely used techniques in proteomics to achieve structural identification and characterization of proteins and peptides, including their variety of proteoforms due to post-translational modifications (PTMs) or protein–protein interactions (PPIs). MALDI-MS...

MCF7 is a commonly used luminal type A non-invasive/poor-invasive human breast cancer cell line that does not usually migrate or invade compared with MDA-MB-231 highly metastatic cells, which emphasize an invasive and migratory behavior. Under special conditions, MCF7 cells might acquire invasive features. The aberration in expression and biologica...

Lysosomal storage diseases (LSDs) are a group of rare and inherited disorders of lysosome function and they are classified into more than 50 types (e.g., mucopolysaccharidoses, neuronal ceroid lipofuscinoses, Fabry's Disease; Pompe Disease, etc.). The majority of LSDs result from defective lysosomal enzyme activity leading to accumulation of endoge...

Breast cancer (BC), one of the most common cancers, is a leading cause of death for women in the United States. An estimated 1 in 8 women in the United States will develop BC in their lifetime. Early diagnosis and treatment of BC is crucial, and protein biomarkers for this disease could make this possible. Mass spectrometry (MS)-based proteomic met...

Human JTB (hJTB) is a gene located on the human chromosome 1 at q21 which is involved in the unbalanced translocation in various types of cancer. JTB protein is ubiquitously present in normal cells and is found to be overexpressed in various types of cancer including prostate and breast cancer. Hence this protein could be a biomarker for tumor mali...

Introduction: Salvelinus namaycush (lake trout) is a top-predator fish in the Great Lakes region. The Great Lakes Fish Monitoring and Surveillance Program (GLFMSP) use lake trout as a bioindicator of chemical stress by monitoring the concentrations of persistent, bioaccumulative and toxic (PBT) chemicals in their bodies. Studies have shown that el...

Jumping translocation breakpoint (JTB) gene acts as a tumor suppressor or an oncogene in different malignancies, including breast cancer (BC), where it was reported as overexpressed. However, the molecular functions, biological processes and underlying mechanisms through which JTB protein causes increased cell growth, proliferation and invasion is...

Mass Spectrometry (MS) allows the analysis of proteins and peptides through a variety of methods, such as Electrospray Ionization-Mass Spectrometry (ESI-MS) or Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS). These methods allow identification of the mass of a protein or a peptide as intact molecules or the identification o...

Zein is a type of prolamin storage protein that has a variety of biomedical and industrial applications. Due to the considerable genetic variability and polyploidity of the starting material, as well as the extraction methods used, the characterization of the protein composition of zein requires a combination of different analytical processes. Ther...

Lake trout (Salvelinus namaycush) are a top‐predator species in the Laurentian Great Lakes that are often used as bioindicators of chemical stressors in the ecosystem. Although many studies are done using these fish to determine concentrations of stressors like legacy persistent, bioaccumulative and toxic chemicals, there are currently no proteomic...

In the three‐step myofibrillogenesis model, mature myofibrils are formed through two intermediate structures: premyofibrils and nascent myofibrils. We have recently reported that several inhibitors of the Ubiquitin Proteosome System, e.g., MG‐132, and DBeQ, reversibly block progression of nascent myofibrils to mature myofibrils. In this investigati...

A near-infrared (NIR) mechanophore was developed and incorporated into a poly(methyl acrylate) chain to showcase the first force-induced NIR chromism in polymeric materials. This mechanophore, based on benzo[1,3]oxazine (OX) fused with a heptamethine cyanine moiety, exhibited NIR mechanochromism in solution, thin-film, and bulk states. The mechanoc...

Breast cancer is an individually unique, multi-faceted and chameleonic disease, an eternal challenge for the new era of high-integrated precision diagnostic and personalized oncomedicine. Besides traditional single-omics fields (such as genomics, epigenomics, transcriptomics and metabolomics) and multi-omics contributions (proteogenomics, proteotra...

Paenarthrobacter nicotinovorans is a soil Gram-positive nicotine-degrading microorganism (NDM) that harbors a 165 kb pAO1 catabolic megaplasmid. The nicotine catabolic genes on pAO1 have been sequenced, but not all the details on the regulation and interplay of this pathway with the general metabolism of the cell are available. To address this issu...

Butanol can be produced biologically through fermentation of lignocellulosic biomass-derived sugars by Gram-positive Clostridium species. For cost-effective production, increased butanol fermentation titers are desired. However, the currently available butanol-fermenting microbes do not tolerate sufficiently high butanol concentrations; thus, new b...

The human genome is sequenced and is comprised of~30,000 genes, making humans just a little bit more complicated than worms or flies. However, complexity of humans is given by proteins that these genes code for, because one gene can produce many proteins mostly through alternative splicing and tissue-dependent expression of particular proteins. In...

Proteomics is the field of study that includes the analysis of proteins, from either a basic science prospective or a clinical one. Proteins can be investigated for their abundance, variety of proteoforms due to post-translational modifications (PTMs), and their stable or transient protein–protein interactions. This can be especially beneficial in...

Using a placebo-controlled, double-blinded, within-participants, randomized, cross-over design, we examined the neurocognitive effects of a: (a) caffeine-containing, adaptogenic herbal-rich natural energy shot (e+ shot), (b) a matched caffeine-containing shot (caffeine), and, (c) a placebo. Participants (n = 30) were low consumers of caffeine witho...

Protein tyrosine phosphorylation is key to activation of receptor tyrosine kinases (RTK) that drive development of some cancers. One challenge of RTK-targeted therapy is identification of those tumors that express non-mutated but activated RTKs. Phosphotyrosine (pTyr) RTK levels should be more predictive of the latter than expressed total protein....

This chapter was previously published as non-open access. This is updated to an open access chapter now.

Lake trout are used as bioindicators for toxics exposure in the Great Lakes ecosystem, however, there is no knowledge about the lake trout proteome. Here we performed the first lake trout (Salvelinus namaycush) liver proteomics study and searched against specific databases: (NCBI and UniProtKB) Salvelinus, Salmonidae, Actinopterygii, the close rela...

Of the 25,000–30,000 human genes, about 2 % code for proteins. However, there are about 1-2 million protein entities. This is primarily due to alternative splicing, post-translational modifications (PTMs) or protein-protein interactions. Proteomics sets out to identify proteins, their sequence and known modifications as well as their quantitation i...

Stilbenes represent a class of compounds with a common 1,2-diphenylethylene backbone that have shown extraordinary potential in the biomedical field. As the most well-known example, resveratrol proved to have anti-aging effects and significant potential in the fight against cardiovascular diseases and some types of cancer. Mass spectrometry is an a...

Better understanding of central nervous system (CNS) molecules can include the identification of new molecules and their receptor systems. Discovery of novel proteins and elucidation of receptor targets can be accomplished using mass spectrometry (MS). We describe a case study of such a molecule, which our lab has studied using MS in combination wi...

Determination of concentration of cortisol in various biological fluids can provide extensive information about a person’s health. Historically, cortisol and its derivatives were (and still are) determined using immunoaffinity-based methods such as colorimetric ELISA assay, chemiluminescent immunoassay, fluorescence assays, radioimmunoassay, electr...

Major depressive disorder (MDD) is common. Despite numerous available treatments, many individuals fail to improve clinically. Diagnosis of MDD continues to be commonly accomplished via behavioral rather than biological methods. Biomarkers may provide objective diagnosis of MDD, and could include measurements of genes, proteins, and patterns of bra...

Within the past years, we have witnessed a great improvement is mass spectrometry (MS) and proteomics approaches in terms of instrumentation, protein fractionation, and bioinformatics. With the current technology, protein identification alone is no longer sufficient. Both scientists and clinicians want not only to identify the proteins, but also to...

Mass spectrometry (MS) is a powerful technique that has various applications including the identification and characterization of proteins, protein-protein interactions and protein post translational modifications, as well as other molecules (i.e. metabolites, lipids, nucleotides and polynucleotides). However, not too many undergraduate students wi...

Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS PAGE) is a method that separates proteins according to their isoelectric points in the first dimension and molecular masses in the second dimension. Evidence is provided that 2D SDS PAGE is reproducible, robust and compatible with SDS in both dimensions including isoe...

ADCs are empowered monoclonal antibodies that are designed to harness their targeting ability by linking them to cell-killing agents. They are made up of three main components, the antibody, linker and the cytotoxic drug. The specificity of the antibody with the antigen on the tumor cell surface helps with its internalization into the cell after wh...

Proteomics is a mass spectrometry-based discipline that aims to analyze proteomes and their functions. Many proteomic studies require well-developed protein databases for reference. However, most proteomes are not well-annotated, aside from model organisms. Techniques like six-frame translation, ab initio gene prediction, and EST databases can aid...

Innovations in approaches for early detection and individual risk assessment of different cancers, including breast cancer (BC), are needed to reduce cancer morbidity and associated mortality. The assessment of potential cancer biomarkers in accessible bodily fluids provides a novel approach to identify the risk and/or onset of cancer. Biomarkers a...

Mass spectrometry (MS) has been increasingly used to study central nervous system (CNS) disorders, including autism spectrum disorders (ASDs). The first studies of ASD using MS focused on the identification of external toxins, but current research is more directed at understanding endogenous protein changes that occur in ASD (ASD proteomics). This...

Fatigue is a common and poorly understood problem that impacts approximately 45% of the United States (US) population. Fatigue has also been associated with fatigue-related driving accidents, school absences, decline in school performance and negative health outcomes. Fatigue has been linked to many diseases and is consistently underreported in med...

Proteomics involves large-scale comprehensive study of specific proteomes which have been widely used in the field of biomarker discovery, drug development, disease diagnosis and therapy. Comprehensive proteomics involve two or more proteomics approaches that are confirmatory, complementary, and/or synergistic. Obstructive sleep apnea (OSA) is a sl...

Mass spectrometry (MS) is the core for advanced methods in proteomic experiments. When effectively used, proteomics may provide extensive information about proteins and their post-translational modifications, as well as their interaction partners. However, there are also many problems that one can encounter during a proteomic experiment, including,...

There are only 30,000 human genes, which, according to the central dogma from biology, it means that there should be 30,000 mRNA and 30,000 proteins. However, there are at least 1-2 million protein entities that are expressed in a cell at a given time. This is primarily due to alternative splicing in different cells and tissues, which may lead to e...

Proteomics, or the large-scale study of proteins, is a post-genomics field that, together with transcriptomics and metabolomics, has moved the study of bacteria to a new era based on system-wide understanding of bacterial metabolic and regulatory networks. The study of bacterial proteins or microbial proteomics has found a wide array of application...

Recent developments of mass spectrometry (MS) allow us to identify, estimate, and characterize proteins and protein complexes. At the same time, structural biology helps to determine the protein structure and its structure-function relationship. Together, they aid to understand the protein structure, property, function, protein-complex assembly, pr...

Obstructive sleep apnea (OSA) affects an estimated 20% of adults worldwide and has been associated with electrical and structural abnormalities of the atria, although the molecular mechanisms are not well understood. Here, we used two‐dimensional polyacrylamide gel electrophoresis (2D PAGE) coupled with nanoliquid chromatography‐tandem mass spectro...

The chapter “2D SDS PAGE in Combination with Western Blotting and Mass Spectrometry Is a Robust Method for Protein Analysis with Many Applications” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Abstract Paenarthrobacter nicotinovorans is a nicotine-degrading microorganism that shows a promising biotechnological potential for the production of compounds with industrial and pharmaceutical importance. Its ability to use nicotine was linked to the presence of the catabolic megaplasmid pAO1. Although extensive work has been performed on the mo...

Obstructive sleep apnea (OSA) affects an estimated 20% of adults worldwide with up to 80% of patients remaining undiagnosed. OSA has been associated with electrical and structural abnormalities of the atria, although the molecular mechanisms are not well understood. We have implemented a rat model of OSA involving the surgical implantation of a tra...

Breast Cancer (BC) remains a major cause of mortality, and early detection is considered important for reducing BC‐associated deaths. Early detection of BC is challenging in young women, due to the limitations of mammography on the dense breast tissue of young women. We recently reported results of a pilot proteomics study, using one‐dimensional po...

Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeu...

Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reprod...

Figure S1 Comparison of up‐regulated proteins between two biological replicates (1 and 2). Figure S2 Comparison of down‐regulated proteins between two biological replicates (1 and 2).

We study the mechanisms involved in the release, triggered by the application of glucose, of insulin entrapped in Fe^(3+)--cross-linked alginate hydrogel particles further stabilized with a polyelectrolyte. Platelet-shaped alginate particles are synthesized containing enzyme glucose oxidase conjugated with silica nanoparticles, which are also entra...

Obstructive sleep apnoea (OSA) affects 9–24% of the adult population. OSA is associated with atrial disease, including atrial enlargement, fibrosis and arrhythmias. Despite the link between OSA and cardiac disease, the molecular changes in the heart which occur with OSA remain elusive. To study OSA-induced cardiac changes, we utilized a recently de...

Fig. S1. An OncoPrint showing the relationship of BCNP1 genetic alterations with TP53, KRAS, MAPK1 (ERK), PIK3CA (PI3K) and AKT2 mutational events. Fig. S2. Effect of PI3K inhibition on BCNP1 phosphorylation at serine residues.