Singh, Sasha A.
Assistant Professor of Medicine, Harvard Medical School;
Associate Scientist, Brigham and Women's Hospital;
Director of Proteomics Research, CICS
Dr. Sasha Singh completed her MSc (Developmental Genetics, 2001) and PhD (Biochemistry/Protein Crystallography, 2007) degrees in the Department of Cell and Systems Biology at the University of Toronto (2007). She then joined the labs of Steen and Steen at Children’s Hospital Boston /Harvard Medical School to complete her post-doctoral studies in mass spectrometry guided research. During this time, she was involved in several projects ranging from high throughput proteomics’ screens to detailed studies on protein posttranslational modifications, as they related to cell cycle/cancer and a number of neurological disorders. She also developed FLEXIQuant, a practical and useful workflow for implementing full-length protein mass spectrometry standards, which in turn developed into a novel in vitro kinase assay, also known as, FLEXIQinase.
Dr. Singh joined the Center for Interdisciplinary Cardiovascular Sciences in 2012. She is very enthusiastic about designing and implementing qualitative and quantitative mass spectrometry guided experiments into the research interests of the center, including developing basic research and target discovery platforms aimed at understanding and tackling cardiovascular diseases.
Publications
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Andraski AB, Sacks FM, Aikawa M, Singh SA
Understanding HDL Metabolism and Biology Through In Vivo Tracer Kinetics.
Tzani A, Haemmig S, Cheng HS, Perez-Cremades D, Heuschkel MA, Jamaiyar A, Singh S, Aikawa M, Yu P, Wang T, Ye S, Feinberg MW, Plutzky J
FAM222A, Part of the BET-Regulated Basal Endothelial Transcriptome, Is a Novel Determinant of Endothelial Biology and Angiogenesis.
Rogers MA, Bartoli-Leonard F, Zheng KH, Small AM, Chen HY, Clift CL, Asano T, Kuraoka S, Blaser MC, Perez KA, Natarajan P, Yeang C, Stroes ESG, Tsimikas S, Engert JC, Thanassoulis G, O'Donnell CJ, Aikawa M, Singh SA, Aikawa E
Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.
Decano JL, Maiorino E, Matamalas JT, Chelvanambi S, Tiemeijer BM, Yanagihara Y, Mukai S, Jha PK, Pestana DVS, D'Souza E, Whelan M, Ge R, Asano T, Sharma A, Libby P, Singh SA, Aikawa E, Aikawa M
Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug-Gene Networks: From Biology to Precision Therapeutics.
Kasai T, Kuraoka S, Higashi H, Delanghe B, Aikawa M, Singh SA
A Combined Gas-Phase Separation Strategy for ADP-ribosylated Peptides.
Perez KA, Deppe DW, Filas A, Singh SA, Aikawa E
Multimodal analytical tools to enhance mechanistic understanding of aortic valve calcification.
Santinelli-Pestana DV, Aikawa E, Singh SA, Aikawa M
PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages.
Blaser MC, Buffolo F, Halu A, Turner ME, Schlotter F, Higashi H, Pantano L, Clift CL, Saddic LA, Atkins SK, Rogers MA, Pham T, Vromman A, Shvartz E, Sukhova GK, Monticone S, Camussi G, Robson SC, Body SC, Muehlschlegel JD, Singh SA, Aikawa M, Aikawa E
Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis.
Raju S, Botts SR, Blaser M, Prajapati K, Ho TWW, Ching C, Galant NJ, Fiddes L, Wu R, Clift CL, Pham T, Lee WL, Singh SA, Aikawa E, Fish JE, Howe KL
Endothelial cells secrete small extracellular vesicles bidirectionally containing distinct cargo to uniquely reprogram vascular cells in the circulation and vessel wall.
Andraski AB, Singh SA, Higashi H, Lee LH, Aikawa M, Sacks FM
The distinct metabolism between large and small HDL indicates unique origins of human apolipoprotein A4.
Bartoli-Leonard F, Zimmer J, Sonawane AR, Perez K, Turner ME, Kuraoka S, Pham T, Li F, Aikawa M, Singh S, Brewster L, Aikawa E
NLRP3 Inflammasome Activation in Peripheral Arterial Disease.
Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, Goettsch C, Hutcheson JD, Rogers MA, Itoh S, Halu A, Lee LH, Blaser MC, Mlynarchik AK, Hagita S, Kuraoka S, Chen HY, Engert JC, Passos LSA, Jha PK, Osborn EA, Jaffer FA, Body SC, Robson SC, Thanassoulis G, Aikawa M, Singh SA, Sonawane AR, Aikawa E
Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.
Katsuki S, Kumar Jha P, Lupieri A, Nakano T, Passos LSA, Rogers MA, Becker-Greene D, Le TD, Decano JL, Ho Lee L, Guimaraes GC, Abdelhamid I, Halu A, Muscoloni A, Vittorio Cannistraci C, Higashi H, Zhang H, Vromman A, Libby P, Keith Ozaki C, Sharma A, Singh SA, Aikawa E, Aikawa M
Proprotein Convertase Subtilisin/Kexin 9 Promotes Macrophage Activation via LDL Receptor-Independent Mechanisms.
Kuo A, Checa A, Niaudet C, Jung B, Fu Z, Wheelock CE, Singh SA, Aikawa M, Smith LEH, Proia RL, Hla T
Murine endothelial serine palmitoyltransferase 1 (SPTLC1) is required for vascular development and systemic sphingolipid homeostasi.
Morgan S, Lee LH, Halu A, Nicolau JS, Higashi H, Ha AH, Wen JR, Daugherty A, Libby P, Cameron SJ, Mix D, Aikawa E, Owens AP, Singh SA, Aikawa M
Identifying novel mechanisms of abdominal aortic aneurysm via unbiased proteomics and systems biology.
Atkins SK, Sonawane AR, Brouwhuis R, Barrientos J, Ha A, Rogers M, Tanaka T, Okui T, Kuraoka S, Singh SA, Aikawa M, Aikawa E
Induced pluripotent stem cell-derived smooth muscle cells to study cardiovascular calcification.
Dacano JL, Aikawa M, Singh SA
Promise of a Novel Bedside-to-Bench Paradigm: Can Percutaneous Coronary Intervention Proteomics Balloon Into Clinical Practice?
Decano JL, Iwamoto Y, Goto S, Lee JY, Matamalas JT, Halu A, Blaser M, Lee LH, Pieper B, Chelvanambi S, Silva-Nicolau J, Bartoli-Leonard F, Higashi H, Shibata H, Vyas P, Wang J, Gostjeva E, Body SC, Singh SA, Aikawa M, Aikawa E
A disease-driver population within interstitial cells of human calcific aortic valves identified via single-cell and proteomic profiling.
Passos LSA, Jha PK, Becker-Greene D, Blaser MC, Romero D, Lupieri A, Sukhova GK, Libby P, Singh SA, Dutra WO, Aikawa M, Levine RA, Nunes MCP, Aikawa E
Prothymosin Alpha: A Novel Contributor to Estradiol Receptor Alpha-Mediated CD8+ T-Cell Pathogenic Responses and Recognition of Type 1 Collagen in Rheumatic Heart Valve Disease.
Sawada H, Katsumata Y, Higashi H, Zhang C, Li Y, Morgan S, Lee LH, Singh SA, Chen JZ, Franklin MK, Moorleghen JJ, Howatt DA, Rateri DL, Shen YH, LeMaire SA, Aikawa M, Majesky MW, Lu HS, Daugherty A
Second Heart Field-derived Cells Contribute to Angiotensin II-mediated Ascending Aortopathies.
Rogers MA, Atkins SK, Zheng KH, Singh SA, Chelvanambi S, Pham TH, Kuraoka S, Stroes ESG, Aikawa M, Aikawa E
Lipoprotein(a) Induces Vesicular Cardiovascular Calcification Revealed With Single-Extracellular Vesicle Analysis.
Tanaka T, Asano T, Okui T, Kuraoka S, Singh SA, Aikawa M, Aikawa E
Computational Screening Strategy for Drug Repurposing Identified Niclosamide as Inhibitor of Vascular Calcification.
Iwata H, Osborn EA, Ughi GJ, Murakami K, Goettsch C, Hutcheson JD, Mauskapf A, Mattson PC, Libby P, Singh SA, Matamalas J, Aikawa E, Tearney GJ, Aikawa M, Jaffer FA
Highly Selective PPARα (Peroxisome Proliferator-Activated Receptor α) Agonist Pemafibrate Inhibits Stent Inflammation and Restenosis Assessed by Multimodality Molecular-Microstructural Imaging.
Kuraoka S, Higashi H, Yanagihara Y, Sonawane AR, Mukai S, Mlynarchik AK, Whelan MC, Hottiger MO, Nasir W, Delanghe B, Aikawa M, Singh SA
A Novel Spectral Annotation Strategy Streamlines Reporting of mono-ADP-ribosylated Peptides Derived from Mouse Liver and Spleen in Response to IFN-γ.
Lupieri A, Nagata Y, Passos LSA, Beker-Greene D, Kirkwood KA, Wylie-Sears J, Alvandi Z, Higashi H, Hung JW, Singh SA, Bischoff J, Levine RA, Aikawa E
Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients.
Hutcheson JD, Schlotter F, Creager MD, Li X, Pham T, Vyas P, Higashi H, Body SC, Aikawa M, Singh SA, Kos L, Aikawa E
Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets.
Decano JL, Singh SA, Bueno CG, Lee LH, Halu A, Chelvanambi S, Matamalas JT, Zhang H, Mlynarchik AK, Qiao J, Sharma A, Mukai S, Wang J, Anderson DG, Ozaki CK, Libby P, Aikawa E, Aikawa M
Systems Approach to Discovery of Therapeutic Targets for Vein Graft Disease PPARα Pivotally Regulates Metabolism, Activation, and Heterogeneity of Macrophages and Lesion Development.
Rogers MA, Hutcheson JD, Okui T, Goettsch C, Singh SA, Halu A, Schlotter F, Higashi H, Wang L, Whelan MC, Mlynarchik AK, Daugherty A, Nomura M, Aikawa M, Aikawa E
Dynamin-related protein 1 inhibition reduces hepatic PCSK9 secretion.
Atkins SK, Singh SA, Aikawa E
Calcific Aortic Valve Disease "Omics"; Is Timely, But Are We Looking Too Late?
Okui T, Iwashita M, Rogers MA, Halu A, Atkins SK, Kuraoka S, Abdelhamid I, Higashi H, Ramsaroop A, Aikawa M, Singh SA, Aikawa E
CROT (Carnitine O-Octanoyltransferase) Is a Novel Contributing Factor in Vascular Calcification via Promoting Fatty Acid Metabolism and Mitochondrial Dysfunction.
Singh SA, Andraski AB, Higashi H, Lee LH, Ramsaroop A, Sacks FM, Aikawa M
Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos.
Schlotter F, de Freitas RCC, Rogers MA, Blaser MC, Wu PJ, Higashi H, Halu A, Iqbal F, Andraski AB, Rodia CN, Kuraoka S, Wen JR, Creager M, Pham T, Hutcheson JD, Body SC, Kohan AB, Sacks FM, Aikawa M, Singh SA, Aikawa E
ApoC-III is a novel inducer of calcification in human aortic valves.
Rogers MA, Buffolo F, Schlotter F, Atkins SK, Lee LH, Halu A, Blaser MC, Tsolaki E, Higashi H, Luther K, Daaboul G, Bouten CVC, Body SC, Singh SA, Bertazzo S, Libby P, Aikawa M, Aikawa E
Annexin A1-dependent tethering promotes extracellular vesicle aggregation revealed with single-extracellular vesicle analysis.
Kawakami R, Katsuki S, Travers R, Romero DC, Becker-Greene D, Araujo Passos LS, Higashi H, Blaser MC, Sukhova GK, Buttigieg J, Kopriva D, Schmidt AM, Anderson DG, Singh SA, Cardoso L, Weinbaum S, Libby P, Aikawa M, Croce K, Aikawa E
S100A9-RAGE Axis Accelerates Formation of Macrophage-Mediated Extracellular Vesicle Microcalcification in Diabetes Mellitus.
Engelbrecht E, Levesque MV, He L, Vanlandewijck M, Nitzsche A, Niazi H, Kuo A, Singh SA, Aikawa M, Holton K, Proia RL, Kono M, Pu WT, Camerer E, Betsholtz C, Hla T
Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta.
Fehr AR, Singh SA, Kerr CM, Mukai S, Higashi H, Aikawa M
The impact of PARPs and ADP-ribosylation on inflammation and host-pathogen interactions.
Arima N, Sasaki Y, Lee LH, Zhang H, Figueiredo JL, Mlynarchik AK, Qiao J, Yamada I, Higashi H, Ha AH, Halu A, Mizuno K, Singh SA, Yamazaki Y, Aikawa M
Multi-organ systems study reveals Igfbp7 as a suppressor of gluconeogenesis after gastric bypass surgery.
Andraski AB, Singh SA, Lee LH, Higashi H, Smith N, Zhang B, Aikawa M, Sacks FM
Effects of Replacing Dietary Monounsaturated Fat With Carbohydrate on HDL (High-Density Lipoprotein) Protein Metabolism and Proteome Composition in Humans.
Goto S, Rogers MA, Blaser MC, Higashi H, Lee LH, Schlotter F, Body SC, Aikawa M, Singh SA, Aikawa E
Standardization of Human Calcific Aortic Valve Disease in vitro Modeling Reveals Passage-Dependent Calcification.
Higashi H, Maejima T, Lee LH, Yamazaki Y, Hottiger MO, Singh SA, Aikawa M
A study into the ADP-ribosylome of IFN-γ-stimulated THP-1 human macrophage-like cells identifies ARTD8/PARP14 and ARTD9/PARP9 ADP-ribosylation.
Higashi H, Maejima T, Lee LH, Yamazaki Y, Hottiger MO, Singh SA, Aikawa M
A study into the ADP-ribosylome of IFN-γ-stimulated THP-1 human macrophage-like cells identifies ARTD8/PARP14 and ARTD9/PARP9 ADP-ribosylation.
Creager MD, Hohl T, Hutcheson JD, Moss AJ, Schlotter F, Blaser MC, Park MA, Lee LH, Singh SA, Alcaide-Corral CJ, Tavares AAS, Newby DE, Kijewski MF, Aikawa M, Di Carli M, Dweck MR, Aikawa E
18F-Fluoride Signal Amplification Identifies Microcalcifications Associated With Atherosclerotic Plaque Instability in Positron Emission Tomography/Computed Tomography Images.
Lee LH, Halu A, Morgan S, Iwata H, Aikawa M, Singh SA
XINA: A Workflow for the Integration of Multiplexed Proteomics Kinetics Data with Network Analysis.
Halu A, Wang JG, Iwata H, Mojcher A, Abib AL, Singh SA, Aikawa M, Sharma A
Context-enriched interactome powered by proteomics helps the identification of novel regulators of macrophage activation.
Schlotter F, Halu A, Goto S, Blaser MC, Body SC, Lee LH, Higashi H, DeLaughter DM, Hutcheson JD, Vyas P, Pham T, Rogers MA, Sharma A, Seidman CE, Loscalzo J, Seidman JG, Aikawa M, Singh SA, Aikawa E
Spatiotemporal Multi-omics Mapping Generates a Molecular Atlas of the Aortic Valve and Reveals Networks Driving Disease.
Singh SA, Aikawa M
Unbiased and targeted mass spectrometry for the HDL proteome.
Lee LH, Andraski AB, Pieper B, Higashi H, Sacks FM, Aikawa M, Singh SA
Automation of PRM-dependent D3-Leu tracer enrichment in HDL to study the metabolism of apoA-I, LCAT and other apolipoproteins.
Iwata H, Goettsch C, Sharma A, Ricchiuto P, Goh WW, Halu A, Yamada I, Yoshida H, Hara T, Wei M, Inoue N, Fukuda D, Mojcher A, Mattson PC, Barabási AL, Boothby M, Aikawa E, Singh SA, Aikawa M
PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation.
Singh SA, Aikawa E, Aikawa M
Current Trends and Future Perspectives of State-of-the-Art Proteomics Technologies Applied to Cardiovascular Disease Research.
Ghiassian SD, Menche J, Chasman DI, Giulianini F, Wang R, Ricchiuto P, Aikawa M, Iwata H, Müller C, Zeller T, Sharma A, Wild P, Lackner K, Singh S, Ridker PM, Blankenberg S, Barabási AL, Loscalzo J
Endophenotype Network Models: Common Core of Complex Diseases.
Goettsch C, Hutcheson JD, Aikawa M, Iwata H, Pham T, Nykjaer A, Kjolby M, Rogers M, Michel T, Shibasaki M, Hagita S, Kramann R, Rader DJ, Libby P, Singh SA, Aikawa E
Sortilin mediates vascular calcification via its recruitment into extracellular vesicles.
Singh SA, Andraski AB, Pieper B, Goh W, Mendivil CO, Sacks FM, Aikawa M
Multiple apolipoprotein kinetics measured in human HDL by high resolution/accurate mass parallel reaction monitoring.
Singh SA, Miyosawa K, Aikawa M
Mass spectrometry meets the challenge of understanding the complexity of the lipoproteome: recent findings regarding proteins involved in dyslipidemia and cardiovascular disease.
Ricchiuto P, Iwata H, Yabusaki K, Yamada I, Pieper B, Sharma A, Aikawa M, Singh SA
mIMT-visHTS: A novel method for multiplexing isobaric mass tagged datasets with an accompanying visualization high throughput screening tool for protein profiling.
Miyosawa K, Watanabe Y, Murakami K, Murakami T, Shibata H, Iwashita M, Yamazaki H, Yamazaki K, Ohgiya T, Shibuya K, Mizuno K, Tanabe S, Singh SA, Aikawa M
New CETP Inhibitor K-312 Reduces PCSK9 Expression: A Potential Effect on LDL Cholesterol Metabolism.
Hutcheson JD, Goettsch C, Pham T, Iwashita M, Aikawa M, Singh SA, Aikawa E
Enrichment of calcifying extracellular vesicles using density-based ultracentrifugation protocol.
Singh SA, Winter D, Kirchner M, Chauhan R, Ahmed S, Ozlu N, Tzur A, Steen JA, Steen H
Co-regulation proteomics reveals substrates and mechanisms of APC/C-dependent degradation.
Itou T, Maldonado N, Yamada I, Goettsch C, Matsumoto J, Aikawa M, Singh S, Aikawa E
Cystathionine γ-lyase Accelerates Osteoclast Differentiation: Identification of a Novel Regulator of Osteoclastogenesis by Proteomic Analysis.
Singh S, Kirchner M, Steen JA, Steen H
A Practical Guide to the FLEXIQuant Method.
Zhang X, Abreu JG, Yokota C, Macdonald BT, Singh S, Coburn KL, Cheong SM, Zhang MM, Ye QZ, Hang HC, Steen H, He X
Tiki1 Is Required for Head Formation via Wnt Cleavage-Oxidation and Inactivation.
Singh SA, Winter D, Bilimoria PM, Bonni A, Steen H, Steen JA
FLEXIQinase, a mass spectrometry-based assay, to unveil multikinase mechanisms.
Akten B, Kye MJ, Hao le T, Wertz MH, Singh S, Nie D, Huang J, Merianda TT, Twiss JL, Beattie CE, Steen JA, Sahin M
Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits.
Singh S, Springer M, Steen J, Kirschner MW, Steen H
FLEXIQuant: a novel tool for the absolute quantification of proteins, and the simultaneous identification and quantification of potentially modified peptides.
Wang Z, Dong G, Singh S, Steen H, Li J
A simple and effective method for detecting phosphopeptides for phosphoproteomic analysis.
Singh S, Stavrinides J, Christendat D, Guttman DS
A phylogenomic analysis of the shikimate dehydrogenases reveals broadscale functional diversification and identifies one functionally distinct subclass.
Singh S, Christendat D
The DHQ-dehydroshikimate-SDH-shikimate-NADP(H) complex: insights into metabolite transfer in the shikimate pathway.
Crystal Growth and Design. 2007;7(11):2153-60
Singh SA, Christendat D
Structure of Arabidopsis dehydroquinate dehydratase-shikimate dehydrogenase and implications for metabolic channeling in the shikimate pathway.
Bonvin J, Aponte RA, Marcantonio M, Singh S, Christendat D, Turnbull JL
Biochemical characterization of prephenate dehydrogenase from the hyperthermophilic bacterium Aquifex aeolicus.
Sun W, Singh S, Zhang R, Turnbull JL, Christendat D
Crystal structure of prephenate dehydrogenase from Aquifex aeolicus. Insights into the catalytic mechanism.
Singh S, Korolev S, Koroleva O, Zarembinski T, Collart F, Joachimiak A, Christendat D
Crystal structure of a novel shikimate dehydrogenase from Haemophilus influenzae.
Hardtke CS, Ckurshumova W, Vidaurre DP, Singh SA, Stamatiou G, Tiwari SB, Hagen G, Guilfoyle TJ, Berleth T
Overlapping and non-redundant functions of the Arabidopsis auxin response factors MONOPTEROS and NONPHOTOTROPIC HYPOCOTYL 4.