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Click on any project title for a more detailed description of the project. For more information about any of these awards (e.g., PI contact information or associated publications), please use the corresponding project number to search for information at theNIH Reporter website. Consistent with NIH policy, abstracts are not available for projects receiving their first award within the past year, so descriptions provided below are from the NCI program director.

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Type Project Year Awarded PI Name(s) Title
Abstract Text (Official)
R21 1R21CA204706-01 2016 BURGETT, ANTHONY WG MASS SPECTROMETRY DETECTION OF DRUGS IN SINGLE BLADDER CANCER CELLS FROM PATIENTS
To use a new single cell mass spectrometry device —the Single probe— to precisely assess and measure the amount of anti-cancer drug present in individual cancer cells, including in bladder cancer cells isolated from patients undergoing chemotherapy.
 
R21 1R21CA206904-01 2016 CHANG, HSUEH-CHIA EGATZ-GOMEZ, ANA ;SENAPATI, SATYAJYOTI A SOLID-STATE NANOPORE MIRNA QUANTIFICATION TECHNOLOGY
To develop a nanopore-based platform for quantification of targeted miRNA from biological samples in such a way that lends itself to point-of-care applications.
 
R21 1R21CA202804-01A1 2016 GAMCSIK, MICHAEL HIGH-THROUGHPUT SCREENING UNDER STATIC OR DYNAMIC HYPOXIA
To develop a novel high-throughput capability for varying oxygen concentrations in microwell plates to improve and amplify the number of studies into the role hypoxia plays in cancer biology and also in assessing the response of cancer cells to different drugs.
 
R21 1R21CA206953-01 2016 HAUN, JERED BRACKSTON TRANSFORMING FLUORESCENCE LIFETIME IMAGING MICROSCOPY INTO A FAST AND SIMPLE PLATFORM FOR HIGH-CONTENT MOLECULAR ANALYSIS
To implement a novel design of nanotechnology-based imaging probes for fluorescence lifetime imaging microscopy, which will improve multiplex imaging capabilities through an imaging-based detection approach complementary to traditional fluorescence.
 
R21 1R21CA202852-01 2016 HELD, JASON M. BIRMAN, VLADIMIR B DEVELOPMENT OF NOVEL CHEMICAL PROBES TO MAP S-NITROSYLATION IN CANCER
To develop a novel probe for S-nitrosothiols in living cells in tissue which would create, for the first time, a tool capable of trapping these reversible covalent binders and allow direct study of the role they play in cell signaling.
 
R21 1R21CA202875-01 2016 LARMAN, HARRY BENJAMIN A HIGHLY MULTIPLEXED GENE EXPRESSION PLATFORM FOR FIXED TISSUE SPECIMENS

 
R21 1R21CA202831-01 2016 LIANG, FU-SEN NOVEL BI-FUNCTIONAL INHIBITORS BLOCKING ONCOMIR BIOGENESIS
To develop a novel bi-functional probe based on a design that would allow for inhibition of specific miRNA; a capability which has been difficult to achieve in a robust way with existing approaches. The proposed approach involves achieving much higher specificity by leveraging Dicer’s role in processing pre-miRNA into miRNA, and a proof-of-concept demonstration will be pursued on a number of well-known miRNA associated with cancer.
 
R21 1R21CA196456-01A1 2016 MATOUSCHEK, ANDREAS DEVELOPMENT OF PROTEASOME ADAPTORS TO CATALYTICALLY DEPLETE SPECIFIC PROTEINS FROM CELLS
To develop a novel strategy for depleting cancer-associated proteins from cells that exploits the proteasome-degradation mechanism in cells but side-steps ubiquitination. It is based on bifunctional molecules that will have both a proteasome binding domain as well as a target protein binding domain and thus shuttle targets directly to the proteasome.  The shuttle molecules are designed to escape the proteasome themselves and to recycle to continue to act on additional targets. The approach is meant to directly address various shortcomings associated with RNAi-based strategies.
 
R21 1R21CA193074-01A1 2016 RECHT, MICHAEL HIGH-THROUGHPUT SCREENING PLATFORM FOR CANCER DRUG DISCOVERY
The goal of this project is to develop a new calorimetry-based high-throughput drug screening platform. The novelty here lies in the use of thermochromic materials in a microfluidic platform to allow for extremely sensitive, label-free probing for very small enthalpy changes arising from binding or enzymatic reactions. The high sensitivity will extend high-throughput screening to non-enzymatic reactions and possibly allow for probing of novel mechanisms of inhibition and should reduce the volume of reagents needed. The proof of concept will involve demonstrating this platform with well-characterized histone deacetylase inhibitors.
 
R21 1R21CA186842-01A1 2016 SADEGHI , SAMAN ELECTROCHEMICAL SYNTHESIS OF RADIOPHARMACEUTICALS
To develop an electrochemical platform for synthesizing PET tracers with 18F-radiolabelled aromatic and heteroaromatic moieties via a small benchtop system that simplifies their production and makes such probes more accessible to the broader research community. The clinical potential, if successful, is improved availability of known and novel PET probes, presently not accessible due to difficulties in synthesis with conventional approaches, which will enhance disease diagnosis and management.
 
R21 1R21CA204563-01 2016 SEGAL, DAVID J CRISPR-BASED EPIGENETIC MODIFIERS
To modify the dCas9 enzyme of the CRISPR system to create a better tool for site specific editing of epigenetic marks. This innovative design involves a unique combination of functional elements yielding a system addressing a variety of shortcomings with regards to existing epigenetic editing approaches.
 
R33 1R33CA196458-01A1 2016 BHARGAVA, ROHIT CHEVILLE, JOHN C TRANSLATIONAL MOLECULAR AND CELLULAR IMAGING TECHNOLOGIES FOR PROSTATE TUMOR PATHOLOGY
To validate a novel clinical diagnostic approach that combines the use of QD-based FISH for multiplexed molecular identification with IR imaging to provide histologic cell/tissue context for each marker measure, and do so using FFPE tissue. The proposal is that this would drastically improve diagnostic accuracy from existing techniques with an AUC of <0.7 up to >0.9 with the proposed approach.
 
R33 1R33CA202900-01 2016 BREUNIG, JOSHUA JOHN A GENETIC TOOLBOX FOR THE IDENTIFICATION AND INTERROGATION OF TUMOR CELLS OF ORIGIN, PROPAGATION, AND RECURRENCE FROM PATIENT-DERIVED ONCOGENIC DRIVERS
To further develop and validate a technique for generating genetically engineered mouse models which has previously been demonstrated for neurology and that allows for multiple driver mutations to arise and be studied in combination. This modular transposon-based system involves delivering a single transposable vector by perinatal electroporation to rapidly develop various combinatorial models and they will demonstrate a capability for quickly obtaining mice that have combinations of known mutations associated with glioblastoma.
 
R33 1R33CA202820-01 2016 GARRAWAY, LEVI A REGEV, AVIV CLINICAL IMPLEMENTATION OF SINGLE CELL TUMOR TRANSCRIPTOME ANALYSIS
To implement a robust single-cell transcript sequencing method in various clinical settings that measures gene expression in hundreds to thousands of individual cells from patient samples. This may provide a more sophisticated capture of the functional heterogeneity that exists in these biospecimens.
 
R33 1R33CA202867-01 2016 NAGRATH, SUNITHA RAMNATH, NITHYA HIGH THROUGHPUT GO CHIP ISOLATION OF LUNG CTCS FOR MOLECULAR DIAGNOSIS AND DRUG TESTING
To optimize and validate their novel liquid biopsy processing platform (the “GO Chip”) for isolating tumor cells from blood samples followed by expansion and genomic analysis of the captured cells, and allow for screening of different drugs on the same platform. Key advantages of the proposed platform is the clever design enabling processing of 10mL of whole blood in one hour, with in situ 3D co-culture and subsequent targeted analysis or drug testing all on the same chip.
 
R33 1R33CA202898-01 2016 QUEIMADO, MARIA DE LURDES A NOVEL MOLECULAR ASSAY FOR EARLY DETECTION AND ASSESSMENT OF CANCER RISK
To optimize and validate a recently developed quantitative DNA damage detection assay for high-throughput screening applications, and to compare it directly with existing techniques to show substantial improvements. Targeted improvements include superior sensitivity, specificity and ability to characterize a broader array of DNA adducts and other lesions than with currently available approaches.
 
R33 1R33CA204582-01 2016 SCARCELLI, GIULIANO BRILLOUIN CONFOCAL MICROSCOPY FOR BIOMECHANICAL STUDIES OF METASTATIC CASCADE IN 3D MICROENVIRONMENTS
To further develop and validate a new microscopy technology, which allows for non-contact based assessment of sample elasticity in 3D. The technology has been demonstrated for non-cancer biological applications, but he is proposing to improve performance for cancer-relevant studies and will demonstrate this with a well-validated in vitro extravasation model.
 
R33 1R33CA206922-01 2016 SCHULTZ, ZACHARY ONLINE RAMAN DIAGNOSTICS OF ONCOMETABOLITES
To optimize a new platform for detecting metabolites based on scattering-enhanced Raman spectroscopy using the PI’s recently developed “sheath-flow” device for introducing samples to the detection area. Importantly, this approach is meant to serve as an alternative to those involving the use of mass spectrometry, which is the predominant tool for studying metabolites, and suffers from a number of important shortcomings for studying this class of analytes.
 
R33 1R33CA202827-01 2016 SIMS, PETER ALAN LARGE-SCALE INTEGRATION OF SINGLE CELL RNA-SEQ AND HIGH-CONTENT IMAGING FOR ANALYZING DRUG RESPONSE IN CANCER
To further develop and validate a recently developed microwell array system for single-cell analysis equipped with high-resolution optics and introducing optically-barcoded beads that will allow correlation of cellular metabolism, protein localization and translation, and cell cycling and signaling of intact cells with single-cell RNA-Seq.
 
R33 1R33CA206949-01 2016 SPICER, TIMOTHY PATRICK ADVANCED DEVELOPMENT AND VALIDATION OF 3 DIMENSIONAL SPHEROID CULTURE OF PRIMARY CANCER CELLS USING NANO3D TECHNOLOGY
To develop and validate a method for bioprinting 3D tumor spheroids, for use in high-throughput screening studies. These tools should contribute to drug repurposing and precision medicine initiatives. The technology involves the use of magnetic nanoparticles that decorate the surface of cells in suspension which facilitates manipulation of these into uniform spheroids that can be centered in each well to further facilitate automated screening of the spheroid arrays
 
R33 1R33CA202834-01A1 2016 TAO, NONGJIAN CHARGE SENSITIVE OPTICAL DETECTION FOR HIGH-THROUGHPUT STUDY OF SMALL MOLECULES
To further develop and validate a biosensor technology that was previously supported with an IMAT R21. These so-called charge-sensitive optical detection probes offer unprecedented capability for measuring small molecule binding kinetics, and further development in this case involves incorporating these sensors into microwell plates and validation for use in high-throughput drug screening applications in several head-to-head comparisons.
 
R33 1R33CA202064-01 2016 WEISSLEDER, RALPH ANALYSIS OF SCANT CANCER CELLS IN FINE NEEDLE ASPIRATES
To optimize and validate a recently developed single-cell analysis platform which can simultaneously profile DNA, mRNA and proteins from cells isolated from fine needle aspirates. The validation work will be done with breast cancer patient samples in tandem with an evaluation of kinase inhibitor treatment to monitor response over time.
 
R21 1R21CA202849-01 2016 GARCIA, ANDRES J THOMAS, SUSAN NAPIER USHEAR TECHNOLOGY FOR CANCER CELL PURIFICAITON
To incorporate their recently developed technique for characterizing an “adhesive force signature” from individual cells into a microfluidic device that provides a cell selection capability for cells based on their respective adhesiveness signatures. The project team propose to develop a platform that may uniquely identify tumor initiating cells based on this signature and using this device, and beyond this the technique may be readily incorporated as an additional stage with other cell selection approaches.
 
R21 1R21CA204707-01 2016 JAHNKE, FRANK A NEW SAMPLE PREPARATION METHOD TO DELVE DEEPER INTO THE PROTEOME
The PI is developing a method to remove problematic abundant proteins from complex human samples. The goal is to remove them selectively under conditions that suppress the very common association of abundant proteins with other species, including potentially interesting candidate biomarker proteins and peptides. The goal is to facilitate de novo cancer biomarker discovery using traditional proteomics tools.
 
R21 1R21CA191243-01A1 2016 SULCHEK, TODD MCDONALD, JOHN F LABEL-FREE MICROFLUIDIC ENRICHMENT OF CANCER CELLS FROM NONCANCER CELLS IN ASCITES FLUID
To develop a new cell sorting device that separates cells based on differences in size and stiffness. These novel sorting parameters serve as a selection approach orthogonal to antibody-based labeling, and the method can be incorporated into existing cell sorting processes. Furthermore, the platform will be developed specifically for use with ascites fluid samples.
 
R21 1R21CA196434-01A1 2016 VANDER GRIEND, DONALD JAMES COLLIER, JOEL H SUPRAMOLECULAR MATRIX MATERIALS FOR PROSTATE CANCER CELL BIOLOGY
To develop a novel matrix for 3D cell culturing that offers significant advantages over existing gels like Matrigel for achieving more representative cultures and also offers built in capacities for monitoring specific biomarkers. The approach is based on synthesized proteins that self-assemble, and allow a variety of controls over the assembly and make-up of the gels.
 
R33 1R33CA204510-01 2016 AKSAN, ALPTEKIN VALIDATION OF A ROOM-TEMPERATURE STORAGE TECHNIQUE FOR PLASMA/SERUM BIOSPECIMENS
To build upon a successful IMAT R21-supported project to develop a capability for storing liquid biospecimens (mainly, human serum) at room temperature for extensive periods using a vitrification approach with a focus on maintaining the stability of the proteinaceous biomarkers in storage. The approach involves the use of an electrospun lyophilizing sponge that dessicates samples into viscous glassy state. Investigators will further develop the technique to stably preserve a larger array of labile and stable proteins with a substantial validation study showing long term preservation stability of 300+ biomarkers compared across fresh, frozen and lyophilized serum over a 36 month period with two large biorepositories.
 
R33 1R33CA202811-01 2016 JOHANN, DONALD TANGREA, MICHAEL DEVELOPMENT AND VALIDATION OF A MICRODISSECTION METHOD TO ADVANCE PRECISION MEDICINE IN THE CLINICAL SETTING
To further develop and validate the emerging expression microdissection (XMD) technique to generally improve several performance parameters for the approach. In brief, XMD is a method for quickly extracting cells of interest from fixed slides by adhering them to a clear film, which is much easier and faster than laser capture microdissection. They research team will demonstrate the potential for this by specifically introducing XMD into clinical workflows
 
R33 1R33CA202822-01 2016 SOKER, SHAY BIOENGINEERED LUNG TUMOR ORGANOIDS FOR DEVELOPMENT OF PERSONALIZED MEDICINE
To develop a computer-based bioprinting approach for making engineered lung tissue organoids consisting of primary lung endothelial and fibroblast cells from needle biopsies embedded in a lung-specific extracellular matrix. The near-term intent for the platform is for expansion of biopsy-derived cells to yield sufficient material to support various molecular profiling analyses.
 
R43 CA203671 2016 OUELLETTE, STEVEN BRADLEY DEVELOPMENT OF AN ASSAY PLATFORM FOR MEASURING ENDOGENOUS KINASE ACTIVITY
Kinase inhibitors are an effective class of targeted therapy for oncology. However, heterogeneous patient response and acquired resistance continues to be a significant clinical and economic burden. To overcome this problem drug developers are pursuing novel kinase inhibitors for existing kinase targets with new modes of inhibition and increased potency, as well as compounds for emerging kinase targets. There is an unmet need in pre-clinical development for assays that measure endogenous kinase activity in disease-relevant cellular models. The long-term goal of this project is to commercialize an assay platform for measuring cell-based endogenous kinase activity. The goal of this Phase I proposal is to further establish feasibility of an assay platform based on cell-permeable peptide substrates specific for a kinase of interest. The peptide amino acid sequences are designed using a recently published algorithm developed by Purdue University researchers called KINATEST-ID. The proof-of-concept demonstration shows that KINATEST-ID designs specific substrates for cytosolic tyrosine kinases based on stringently curated endogenous kinase substrate sequences. In this proposal, successful completion of the aims will result in the expansion of the platform to show feasibility for receptor tyrosine kinases (RTKs). In the first ai we will identify endogenous substrates for RTKs in disease-relevant cellular models that will be used to design specific substrates for RTKs of interest using KINATEST-ID. This will be accomplished using a novel method known as kinase assay linked to phosphoproteomics (KALIP), which identifies endogenous sequences for the target RTK. The identified sequences will then be used as input data for the KINATEST-ID algorithm to design candidate RTK substrate sequences. In the second aim, designed substrate sequences will be synthesized and empirically validated for kinase specificity, and assay performance will be analytically characterized in vitro. Finally, substrates that meet quantitative criteriafor specificity and assy performance in the second aim will be modified and optimized for use in cell-based applications. Successful completion of the aims will result in a panel of prototype cell-based assays for measuring endogenous RTK activity, and a validated R&D pipeline for further expansion of the assay platform. Phase II of this project will focus on developing partnerships to bring this assay platform to the drug discovery market, expansion into additional kinases, and adapting the assay for use in patient derived samples, such as biopsies or circulating tumor cells.
 
R43 CA203675 2016 KLUGE, JONATHAN AUGUST SILK-BASED BLOOD SAMPLE STABILIZATION FOR PROSTATE CANCER DIAGNOSTICS
There is a critical need for a blood sample preparation and processing method that can preserve integrity and improve downstream analysis, while being completely free of cold storage requirements. Such a technology would allow clinicians and patients to collect blood samples for cancer screening, monitoring and/or diagnosis comfortably from patient's homes, obviating the need for outpatient lab visits. Vaxess Technologies is developing a set of biomaterial-based approaches that improves the stability of a wide range of samples using a novel silk protein matrix. The objective of this proposal is to characterize the ability of a silk matrix to stabilize a panel of metabolomic prostate cancer biomarkers in a blood sample. The enhanced performance of silk- based protection will be compared to other similar methods (dried blood spot (DBS) cards) and the gold standard (frozen storage). We anticipate that the use of silk will allow for minimally- or non-invasive sample collection routes, and will provide comparable analyte retention to the current gold standard, frozen storage, while improving recovery as compared to commercially-available DBS cards. Vaxess has extensive preliminary data demonstrating the use of silk to stabilize antibodies, plasma proteins and nucleic acids from complex fluids such as whole blood, plasma, serum, and saliva. We anticipate being able to do the same with blood analytes, as proposed here. In the first aim, we will form serum-laden silk matrices and quantitate metabolomic prostate cancer marker levels. This will be accomplished by using mass spectrometry to measure analyte recovery from silk matrices and comparing the yields directly to frozen controls or DBS cards. Modifications of silk molecular weight and its net charge can systematically change proteomic interactions, and thus provides a route to study the mechanistic underpinnings of silk stabilization in the context of sample recovery. In a second aim, we will compare the stability of markers identified in Aim 1 to frozen control samples and DBS cards when all have been treated at various temperatures and humidity levels. The expected outcome of these studies will be the development of a silk-based sample preparation method for cancer-specific analytes that will improve downstream sample processing. The rationale for the proposed research is that, once recovery and stability of these biomarkers is proven to be augmented by a silk encapsulate, diagnostic kits can be outfitted with various silk formats, which can then be used as a platform system for full validation in follow-on studies. Success with the planned approach can positively impact many areas of need in the field of cancer diagnostics, including early detection, screening, and clinical diagnosis, by increasing overall access to precise analytics and by reducing pre-analytical variations that affect sample quality. Furthermore, by offering methods to interface with finger-prick volumes of whole blood, a silk-based stabilization system could be used without a phlebotomist and thus circumvent the resource requirements of the outpatient clinic.