Nicholas Saccomano - Academia.edu (original) (raw)
Papers by Nicholas Saccomano
Nature Precedings, Jul 9, 2010
Recently, we reported an aptamer-based, highly multiplexed assay for the purpose of biomarker ide... more Recently, we reported an aptamer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (up to 200 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community.
The translation of biomarkers from pre-clinical model systems to human conditions has proven to b... more The translation of biomarkers from pre-clinical model systems to human conditions has proven to be challenging. One approach to this issue is through the use of a rapid, highly multiplexed, quantitative assay solution targeted at human proteins and cross-species orthologs. SOMAscan™, a high-throughput, multiplexed proteomic assay (Ver. 3 1100 protein analytes), simultaneously measures native folded proteins directly from small volumes of biological samples such as plasma, tissue or cell culture. A series of early experiments were examined in Non-Small Cell Lung Cancer (NSCLC) to identify translatable proteins in cell culture and mouse xenograft model systems as well as across human NSCLC tumor and serum. Drug sensitive and resistant NSCLC cell lines demonstrated profound differences in protein concentrations in response to drug treatment. Comparison of cell findings with tumor xenografts showed 22 (of 93) proteins in common. Experiments conducted in NSCLC clinical patients found 11 ...
Cancer Research, 2013
Using a sensitive proteomics platform that can precisely and simultaneously measure 1129 distinct... more Using a sensitive proteomics platform that can precisely and simultaneously measure 1129 distinct proteins (SOMAscan™), we profiled the proteomic changes in cancer cell lines and xenograft models following exposure to several oncological agents. Our goals were to identify novel biomarkers and drug targets, and to map out pharmacological MOA, with the ultimate goal of assessing the translatability of in vitro and preclinical models to human patients. We have generated multiple successful examples of using our platform in this manner. We treated a breast cancer cell line MCF-7 with eight pharmacological agents, including TamoxifenTM and TaxolTM. We have assessed PKC-δ resistant and sensitive lung cancer cell lines with a PKC-δ inhibitor, and profiled protein changes in response to these compounds. To assess how well in vitro models translate to preclinical models, we profiled protein changes in HCC827 (sensitive) or H1299 (resistant) cell lines treated with erlotinib (TarcevaTM), and ...
PLOS ONE, Oct 17, 2011
Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker iden... more Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (upwards of 60 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community.
PLoS ONE, 2011
Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker iden... more Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (upwards of 60 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community.
PROBLEM TO BE SOLVED: To obtain the subject new polypeptide derived from the Agelenopsis aperta s... more PROBLEM TO BE SOLVED: To obtain the subject new polypeptide derived from the Agelenopsis aperta spider toxin, having a specific amino acid sequence, exhibiting calcium channel-blocking activity, useful for control of harmful invertebrate insects and treatment of hypertension, myocardosis, arrhythmia etc. SOLUTION: This polypeptide is a virtually pure new polypeptide (or its salt) having an amino acid sequence expressed by the formula, having calcium channel-blocking activity, and being useful for control harmful invertebrate insects and treatment of angina, hypertension, superior ventricle arrhythmia, premature birth, Raynaud disease, etc., as a calcium channel blocker. This polypeptide is obtained by dilution of the whole venom of Agelenopsis aperta spider followed by fractionation with the reverse phase high performance liquid chromatography where the above diluted venom is loaded on a C-18 Vydac column and subjected to elution with a solvent system using a linear gradient program...
PROBLEM TO BE SOLVED: To obtain a novel polypeptide contained in a fraction prepared from a crude... more PROBLEM TO BE SOLVED: To obtain a novel polypeptide contained in a fraction prepared from a crude venom of a spider belonging to Agelenopsis aperta and useful as an agent for blocking a Ca-channel of neuron, muscle cells, etc., of an invertebrate and a vertebrate, etc. SOLUTION: This novel polypeptide (salt) is contained in a fraction from a crude venom of a spider belonging to Agelenopsis aperta, which elutes from a 22mm×250mm column of C-18 Vydac (Vydac TM) having a pore size of 300Å and a grain size of 10μm for about 43min with a solvent system programmed by the following linear gradient: a flow rate 15ml/min, from 5% to 80% in B and from 95% to 80% in A (A is a 0.1% TFA aqueous solution; B is acetonitrile) from 0 to 30min; and subsequently, from 20% to 70% in B and from 80% to 30% in A from 30min to 55min. The polypeptide has an amino acid sequence expressed by the formula at the amino terminal and a molecular weight of about 20,000. Further, the peptide blocks a Ca-channel of n...
Journal for ImmunoTherapy of Cancer
BackgroundPoly(ADP-ribose) polymerase inhibitors (PARPi) have improved the outcomes of BRCA-assoc... more BackgroundPoly(ADP-ribose) polymerase inhibitors (PARPi) have improved the outcomes of BRCA-associated breast cancer; however, treatment responses are often not durable. Our preclinical studies demonstrated that PARPi activates the cGAS/STING pathway and recruitment of anti-tumor CD8+ T-cells that are required for tumor clearance [1]. These studies contributed to development of clinical trials testing PARPi plus immune checkpoint blockade (ICB). Unfortunately, early phase trials of PARPi + ICB have not yet suggested efficacy will be superior to PARPi monotherapy. Lack of demonstrated clinical synergy between PARPi + ICB underscores the need to study the tumor microenvironment (TME) during PARPi therapy to identify optimal strategies to enhance T-cell activation. We recently showed that PARPi induces CSF-1R+ suppressive tumor associated macrophages (TAMs) that restrict antitumor immune responses, contributing to PARPi resistance [2]. Removing TAMs with anti-CSF-1R therapy in combinat...
Journal of Organic Chemistry, 1992
... V. John Jasys, Paul R. Kelbaugh, Deane M. Nason, Douglas Phillips, Kenneth J. Rosnack, James ... more ... V. John Jasys, Paul R. Kelbaugh, Deane M. Nason, Douglas Phillips, Kenneth J. Rosnack, James T. Forman, Nicholas A. Saccomano, Justin G. Stroh, and Robert A. Volkmann* ... (6) Jasys, VJ; Kelbaugh, P. R.; Nason, DM; Phillips, D.; Sacco-mano, NA; Volkmann, R. A ...
Tetrahedron Letters, 1987
Nature Precedings, Jul 9, 2010
Recently, we reported an aptamer-based, highly multiplexed assay for the purpose of biomarker ide... more Recently, we reported an aptamer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (up to 200 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community.
The translation of biomarkers from pre-clinical model systems to human conditions has proven to b... more The translation of biomarkers from pre-clinical model systems to human conditions has proven to be challenging. One approach to this issue is through the use of a rapid, highly multiplexed, quantitative assay solution targeted at human proteins and cross-species orthologs. SOMAscan™, a high-throughput, multiplexed proteomic assay (Ver. 3 1100 protein analytes), simultaneously measures native folded proteins directly from small volumes of biological samples such as plasma, tissue or cell culture. A series of early experiments were examined in Non-Small Cell Lung Cancer (NSCLC) to identify translatable proteins in cell culture and mouse xenograft model systems as well as across human NSCLC tumor and serum. Drug sensitive and resistant NSCLC cell lines demonstrated profound differences in protein concentrations in response to drug treatment. Comparison of cell findings with tumor xenografts showed 22 (of 93) proteins in common. Experiments conducted in NSCLC clinical patients found 11 ...
Cancer Research, 2013
Using a sensitive proteomics platform that can precisely and simultaneously measure 1129 distinct... more Using a sensitive proteomics platform that can precisely and simultaneously measure 1129 distinct proteins (SOMAscan™), we profiled the proteomic changes in cancer cell lines and xenograft models following exposure to several oncological agents. Our goals were to identify novel biomarkers and drug targets, and to map out pharmacological MOA, with the ultimate goal of assessing the translatability of in vitro and preclinical models to human patients. We have generated multiple successful examples of using our platform in this manner. We treated a breast cancer cell line MCF-7 with eight pharmacological agents, including TamoxifenTM and TaxolTM. We have assessed PKC-δ resistant and sensitive lung cancer cell lines with a PKC-δ inhibitor, and profiled protein changes in response to these compounds. To assess how well in vitro models translate to preclinical models, we profiled protein changes in HCC827 (sensitive) or H1299 (resistant) cell lines treated with erlotinib (TarcevaTM), and ...
PLOS ONE, Oct 17, 2011
Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker iden... more Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (upwards of 60 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community.
PLoS ONE, 2011
Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker iden... more Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (upwards of 60 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community.
PROBLEM TO BE SOLVED: To obtain the subject new polypeptide derived from the Agelenopsis aperta s... more PROBLEM TO BE SOLVED: To obtain the subject new polypeptide derived from the Agelenopsis aperta spider toxin, having a specific amino acid sequence, exhibiting calcium channel-blocking activity, useful for control of harmful invertebrate insects and treatment of hypertension, myocardosis, arrhythmia etc. SOLUTION: This polypeptide is a virtually pure new polypeptide (or its salt) having an amino acid sequence expressed by the formula, having calcium channel-blocking activity, and being useful for control harmful invertebrate insects and treatment of angina, hypertension, superior ventricle arrhythmia, premature birth, Raynaud disease, etc., as a calcium channel blocker. This polypeptide is obtained by dilution of the whole venom of Agelenopsis aperta spider followed by fractionation with the reverse phase high performance liquid chromatography where the above diluted venom is loaded on a C-18 Vydac column and subjected to elution with a solvent system using a linear gradient program...
PROBLEM TO BE SOLVED: To obtain a novel polypeptide contained in a fraction prepared from a crude... more PROBLEM TO BE SOLVED: To obtain a novel polypeptide contained in a fraction prepared from a crude venom of a spider belonging to Agelenopsis aperta and useful as an agent for blocking a Ca-channel of neuron, muscle cells, etc., of an invertebrate and a vertebrate, etc. SOLUTION: This novel polypeptide (salt) is contained in a fraction from a crude venom of a spider belonging to Agelenopsis aperta, which elutes from a 22mm×250mm column of C-18 Vydac (Vydac TM) having a pore size of 300Å and a grain size of 10μm for about 43min with a solvent system programmed by the following linear gradient: a flow rate 15ml/min, from 5% to 80% in B and from 95% to 80% in A (A is a 0.1% TFA aqueous solution; B is acetonitrile) from 0 to 30min; and subsequently, from 20% to 70% in B and from 80% to 30% in A from 30min to 55min. The polypeptide has an amino acid sequence expressed by the formula at the amino terminal and a molecular weight of about 20,000. Further, the peptide blocks a Ca-channel of n...
Journal for ImmunoTherapy of Cancer
BackgroundPoly(ADP-ribose) polymerase inhibitors (PARPi) have improved the outcomes of BRCA-assoc... more BackgroundPoly(ADP-ribose) polymerase inhibitors (PARPi) have improved the outcomes of BRCA-associated breast cancer; however, treatment responses are often not durable. Our preclinical studies demonstrated that PARPi activates the cGAS/STING pathway and recruitment of anti-tumor CD8+ T-cells that are required for tumor clearance [1]. These studies contributed to development of clinical trials testing PARPi plus immune checkpoint blockade (ICB). Unfortunately, early phase trials of PARPi + ICB have not yet suggested efficacy will be superior to PARPi monotherapy. Lack of demonstrated clinical synergy between PARPi + ICB underscores the need to study the tumor microenvironment (TME) during PARPi therapy to identify optimal strategies to enhance T-cell activation. We recently showed that PARPi induces CSF-1R+ suppressive tumor associated macrophages (TAMs) that restrict antitumor immune responses, contributing to PARPi resistance [2]. Removing TAMs with anti-CSF-1R therapy in combinat...
Journal of Organic Chemistry, 1992
... V. John Jasys, Paul R. Kelbaugh, Deane M. Nason, Douglas Phillips, Kenneth J. Rosnack, James ... more ... V. John Jasys, Paul R. Kelbaugh, Deane M. Nason, Douglas Phillips, Kenneth J. Rosnack, James T. Forman, Nicholas A. Saccomano, Justin G. Stroh, and Robert A. Volkmann* ... (6) Jasys, VJ; Kelbaugh, P. R.; Nason, DM; Phillips, D.; Sacco-mano, NA; Volkmann, R. A ...
Tetrahedron Letters, 1987