William Bocik
A5067383849- Advanced Proteomics Techniques and Applications
- Ubiquitin and proteasome pathways
- Mass Spectrometry Techniques and Applications
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Research Studies
- Neuroblastoma Research and Treatments
- Immune cells in cancer
- Advanced Biosensing Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Melanoma and MAPK Pathways
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Autophagy in Disease and Therapy
- Sarcoma Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Glycosylation and Glycoproteins Research
- Circular RNAs in diseases
- vaccines and immunoinformatics approaches
- Inflammatory mediators and NSAID effects
- Metabolomics and Mass Spectrometry Studies
- DNA Repair Mechanisms
- Monoclonal and Polyclonal Antibodies Research
Frederick National Laboratory for Cancer Research
2018-2024
Leidos (United States)
2021
Johns Hopkins University
2009-2017
University of Toledo
2002
Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification metabolomic data on 99 treatment-naive GBMs provides insights GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 PLCG1) as potential switches mediating oncogenic pathway activation, well targets for EGFR-, TP53-, RB1-altered tumors. Immune...
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences perturbations to the p53 Wnt/β-catenin pathways, identified potential role for circRNAs in epithelial-mesenchymal transition, provided information about proteomic markers clinical genomic tumor subgroups, including relationships known druggable pathways. An extensive genome-wide...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 tissues. Proteomic, phosphoproteomic, glycoproteomic analyses were used to characterize proteins their modifications. In addition, whole-genome sequencing, whole-exome methylation, RNA sequencing...
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins phosphosites, prioritizes copy number drivers, highlights an oncogenic role for RNA processing genes. investigation mutual exclusivity between FAT1 truncating mutations 11q13.3 amplifications reveals dysregulated actin dynamics as common functional consequence. Phosphoproteomics characterizes two...
Methodologies that facilitate high-throughput proteomic analysis are a key step toward moving proteome investigations into clinical translation. Data independent acquisition (DIA) has potential as analytical method due to the reduced time needed for sample analysis, well its highly quantitative accuracy. However, limiting feature of DIA methods is sensitivity detection low abundant proteins and depth coverage, which other mass spectrometry approaches address by two-dimensional fractionation...
Abstract Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings clinical applications becomes imperative. To meet the rigorous regulatory standards laboratories, development a protein MS assay necessitates adherence stringent criteria. illustrate process, this project focused on using thyroglobulin...
Abstract Ube2g2 is an E2 enzyme which functions as part of the endoplasmic reticulum‐associated degradation (ERAD) pathway responsible for identification and misfolded proteins in reticulum. In tandem with a cognate E3 ligase, assembles K48‐linked polyubiquitin chains then transfers them to substrate, leading ultimately proteasomal polyubiquitin‐tagged substrate. We report here solution structure backbone dynamics solved by nuclear magnetic resonance spectroscopy. Although agrees well...
Reference materials are vital to benchmarking the reproducibility of clinical tests and essential for monitoring laboratory performance proteomics. The reference material utilized mass spectrometric analysis human proteome would ideally contain enough proteins be suitably representative proteome, as well exhibit a stable protein composition in different batches sample regeneration. Previously, Clinical Proteomic Tumor Analysis Consortium (CPTAC) PDX-derived comparative (CompRef) longitudinal...
A primary goal of the US National Cancer Institute's Ras initiative at Frederick Laboratory for Research is to develop methods quantify RAS signaling facilitate development novel cancer therapeutics. We use targeted proteomics technologies a community resource consisting 256 validated multiple reaction monitoring (MRM)-based, multiplexed assays quantifying protein expression and phosphorylation through receptor tyrosine kinase, MAPK, AKT networks. As proof concept, we response melanoma (A375...
Immunotherapies are revolutionizing cancer care, producing durable responses and potentially cures in a subset of patients. However, response rates low for most tumors, grade 3/4 toxicities not uncommon, our current understanding tumor immunobiology is incomplete. While hundreds immunomodulatory proteins the microenvironment shape anti-tumor response, few them can be reliably quantified. To address this need, we developed multiplex panel targeted proteomic assays targeting 52 peptides...
Ube2g2 is a human ubiquitin conjugating (E2) enzyme involved in the endoplasmic reticulum-associated degradation pathway, which responsible for identification and of unfolded misfolded proteins reticulum compartment. The Ube2g2-specific role assembly Lys-48-linked polyubiquitin chains, constitutes signal proteasomal when attached to substrate protein. NMR chemical shift perturbation paramagnetic relaxation enhancement approaches were employed characterize binding interaction between...
The ubiquitin conjugating enzyme Ube2g2 together with its cognate E3 ligase gp78 catalyzes the synthesis of lysine-48 polyubiquitin chains constituting signals for proteasomal degradation misfolded proteins in endoplasmic reticulum. Here, we employ NMR spectroscopy combination single-turnover diubiquitin formation assays to examine role RING domain from catalytic activation Ube2g2∼Ub conjugates. We find that approximately 60% conjugates occupy a closed conformation absence gp78-RING,...
The ATM serine/threonine kinase (HGNC: ATM) is involved in initiation of repair DNA double-stranded breaks, and inhibitors are currently being tested as anti-cancer agents clinical trials, where pharmacodynamic (PD) assays crucial to help guide dose scheduling support mechanism action studies. To identify quantify PD biomarkers inhibition, we developed analytically validated a 51-plex assay (DDR-2) quantifying protein expression damage-responsive phosphorylation. median lower limit...
Introduction Immunotherapy is an effective treatment for a subset of cancer patients, and expanding the benefits immunotherapy to all patients will require predictive biomarkers response immune-related adverse events (irAEs). To support correlative studies in clinical trials, we are developing highly validated assays quantifying immunomodulatory proteins human biospecimens. Methods Here, developed panel novel monoclonal antibodies incorporated them into novel, multiplexed, immuno-multiple...
Abstract RAS genes are frequently mutated in cancer and have for decades eluded effective therapeutic attack. The National Cancer Institute’s Initiative has a focus on understanding pathways discovering therapies RAS-driven cancers. Part of these efforts is the generation novel reagents to enable quantification network proteins. Here we present dataset describing development, validation (following consensus principles developed by broader research community), distribution 104 monoclonal...
Abstract Immunotherapies are revolutionizing cancer care, but many patients do not achieve durable responses and immune-related adverse events difficult to predict. Quantifying the hundreds of proteins involved in immunity has potential provide biomarkers monitor predict tumor response. We previously developed robust, multiplexed quantitative assays for immunomodulatory using targeted mass spectrometry, providing measurements that can be performed reproducibly harmonized across laboratories....
Abstract Background: Neuroblastoma (NB) is the 3rd most common childhood cancer and accounts for 15% of all pediatric deaths. Recently, immunotherapy using monoclonal antibodies targeting GD2 have improved survival rates some patients with NB. Unfortunately, this response not uniform, suggesting an incomplete understanding underlying immune biology. Large-scale sequencing patient tumors suggested that NB has diverse microenvironments (TMEs), which are associated MYCN-amplification (A)...
Abstract Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings clinical applications becomes imperative. To meet the rigorous regulatory standards laboratories, development a protein MS assay necessitates adherence stringent criteria. illustrate process, this project focused on using thyroglobulin...
Abstract Elevated expression of Inducible Nitric oxide Synthase-2 (NOS2) occurs during acute and chronic inflammation wound healing processes however, it is also a predictor bad prognosis in aggressive ER-negative tumors. Overexpression NOS2 correlates with other prognostic biomarkers making unique multifunctional oncoprotein. Cyclooxygenase-2 (COX2) another enzyme associated cancer overexpressed >50% breast cancers. In our previous studies, we have shown that NOS2/COX2 co-expression...