CRTP CCR Dedicated Cores

Division Of Basic Sciences - Nci

Investigators

Abstract

CCR Volume Electron Microscopy (CVEM) enables imaging of cells and tissues in 3D and at nanoscale resolution to solve important problems in cancer biology. The group offers expertise in 3D imaging through its development and deployment of techniques in focused ion beam scanning electron microscopy (FIB-SEM), array (AT) and electron tomography (ET), as well as other complementary and correlative methods. In accordance with the needs of CCR investigators, research in the laboratory focuses on identifying cellular structures, interactions, motility, metabolism, and other cell functions. CVEM is a fully collaborative resource that provides support in specimen preparation and characterization, as well as image analysis, for which the group develops unique applications to quantify cellular features using artificial intelligence (AI) and machine learning (ML) algorithms. In FY25, CVEM collaborated with seven (7) CCR investigators on cancer-related projects for imaging of cancer and immune cells, spheroids, patient-derived biopsy specimen, and cancer patient-derived cell samples. In addition, CVEM also developed two (2) new AI models to accurately segment neclei and lipid droplets. The Electron Microscopy Laboratory (EML) provides CCR investigators with unique electron microscopy (EM) expertise in electron tomography, ImmunoEM, negative stain and ultrastructure analysis, nanoparticle characterization, and Correlative Light Electron Microscopy (CLEM), as well as access to cutting-edge EM technologies like Transmission Electron (TEM) and Scanning Electron Microscopy (SEM) to explore new and challenging problems in cancer research. The lab provides complete specimen preparation services, including shipment of fixative, processing, embedding, sectioning, and imaging of samples, as well as develops custom EM protocols that are tailored to meet the specific needs of CCR scientists. In FY25, EML supported eighteen (18) individual CCR and NIH labs with completing 41 unique EM projects. In addition, EML provided hands-on training for seven (7) CCR staff scientists, as well as seven hundred (700) hours of EM access to the National Eye Institute (NEI), with which CCR has a pre-negotiated memorandum of understanding, to support ongoing NEI research projects. EML has also made strides to increase efficiency by developing automated protocols for TEM processing and immunoEM labeling, resulting in a 50-75% reduction in processing times. The Genomics Technologies Laboratory (GTL) is an integrated molecular biology laboratory that focuses on the development of genetics and genomics technologies, and data analysis and information management tools. The laboratory develops integrated strategies using multiple advanced genomics technology platforms that maximize the value of research or clinical samples, and lead to the identification of pathways, genes, or gene products involved in the development of cancer. GTL also provides expertise in the assembly of genetic or expression profiles for the identification of prognostic and diagnostic indicators in complex research and clinical samples. Over the past year, GTL supported one-hundred eighteen (118) individual projects primarily focused on cancer research. Of note, GTL recently developed assays to analyze minimally-invasive patient-derived liquid biopsy samples to identify novel cancer biomarkers for early disease detection and tracking the efficacy of cancer treatment. In collaboration with CCR investigators, this work led to two (2) novel patents filed with the NCI technology transfer office, as well as receiving the 2025 NCI Director's Award for GTL's contributions to cancer research and the improvement of all cancer patients lives. The Protein Expression Laboratory (PEL) provides CCR investigators with access to a vast catalog of hundreds of protein expression plasmids and clones, as well as services in coning optimization, eukaryotic and microbial expression, and protein purification. PEL specializes in parallel small-scale screening, which utilizes a 'purity first' platform to perform side-by-side comparisons of multiple expression modalities to identify the most purifiable conditions for each target protein. In FY25, PEL supported twenty-six (26) investigators in completing fifty-one (51) total projects, including the production of a previously unknown novel protein member of the topoisomerase family. The Protein Characterization Lab (PCL) aids CCR investigators with advancing their understanding of how cellular functions influence cancer development, progression, and treatment. PCL utilizes mass spectrometry (MS), gas and liquid chromatography, and surface plasmon resonance to offer expertise to CCR investigators in the areas of protein and protein-complex characterization, post-translational protein modifications, and global and targeted protein and metabolite identification and quantification. The lab engages in both short- and long-term collaborations, supporting 92 investigators on 240 projects that resulted in 18 publications in FY25. In addition, PCL provides training opportunities for CCR researchers focused on applying MS techniques and interpreting MS data. As needed, the PCL develops and implements new technologies to support CCR research in identifying, characterizing, and quantifying target proteins, metabolites, small molecules, and biomarkers of interest in cancer. Recently, PCL collaborated with multiple CCR investigators to develop unique immunopeptidomics assays to discover and verify novel antigens involved in T-cell maturation, as well as the identification of human orphan T-cell neoantigens. The Optical Microscopy and Analysis Laboratory (OMAL) provides CCR investigators with access to the latest fluorescence, atomic force, confocal, and super-resolution imaging systems. In FY25, OMAL supported fifty (50) CCR labs with developing translational cancer models that use cutting-edge microscopy technologies to quantitatively and spatially understand the molecular basis of 3D cell organization, motility, invasion, and differentiation in cancer. In addition, the lab provides computational support for image visualization and analysis, as well as offering training and education on microscope use, image interpretation, and analysis for CCR investigators. The CCR Single Cell Analysis Facility (SCAF) provides support for the highest value single-cell sequencing and spatial 'omics technologies to CCR Investigators. Specifically, technologies within the SCAF assist CCR researchers to answer complex questions in cancer biology by identifying new or rare cell populations, characterizing tumor cell heterogeneity, and preserving precious tumor tissue samples for determining cell-cell interactions during tumor evolution and cancer therapy. Through an integrated support model for projects from experimental design, sample preparation advice, single cell partitioning, sequencing library generation, and informatic processing and interpretation, CCR SCAF aims to provide a support experience that makes single cell biology more readily accessible to CCR investigators. Over the past year, SCAF has collaborated with more than forty (40) CCR labs to complete eighty (80) projects. Specific support included generation of over six-hundred twenty (620) droplet-based libraries and analysis of seventy-five (75) spatial transcriptomics and fifty (50) single-cell spatial transcriptomics slides, all in support of ongoing CCR projects.