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Author Ian A Blair

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Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells.

Yi Xu, Yang Zhang, Juan C García-Cañaveras, Lili Guo, Mengyuan Kan, Sixiang Yu, Ian A Blair, Joshua D Rabinowitz, Xiaolu Yang,

Embryonic stem cells can propagate indefinitely in a pluripotent state, able to differentiate into all types of specialized cells when restored to the embryo. What sustains their pluripotency during propagation remains unclear. Here, we show that core pluripotency factors OCT4 and SOX2 suppress chaperone-mediated autophagy (CMA), a selective form of ... Read more >>

Science (Science (New York, N.Y.))
[2020, 369(6502):397-403]

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Changes in Aged Fibroblast Lipid Metabolism Induce Age-dependent Melanoma Cell Resistance to Targeted Therapy Via the Fatty Acid Transporter FATP2.

Gretchen M Alicea, Vito W Rebecca, Aaron R Goldman, Mitchell E Fane, Stephen M Douglass, Reeti Behera, Marie R Webster, Curtis H Kugel, Brett L Ecker, M Cecilia Caino, Andrew V Kossenkov, Hsin-Yao Tang, Dennie T Frederick, Keith T Flaherty, Xiaowei Xu, Qin Liu, Dmitry I Gabrilovich, Meenhard Herlyn, Ian A Blair, Zachary T Schug, David W Speicher, Ashani T Weeraratna,

Older melanoma patients (>50 years old) have poorer prognoses and response rates to targeted therapy compared to young patients (<50 years old), which can be driven, in part, by the aged microenvironment. Here, we show that aged dermal fibroblasts increase the secretion of neutral lipids, especially ceramides. When melanoma cells ... Read more >>

Cancer Discov (Cancer discovery)
[2020, :]

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FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome.

Fuming Li, Peiwei Huangyang, Michelle Burrows, Kathy Guo, Romain Riscal, Jason Godfrey, Kyoung Eun Lee, Nan Lin, Pearl Lee, Ian A Blair, Brian Keith, Bo Li, M Celeste Simon,

The crosstalk between deregulated hepatocyte metabolism and cells within the tumour microenvironment, as well as the consequent effects on liver tumorigenesis, are not completely understood. We show here that hepatocyte-specific loss of the gluconeogenic enzyme fructose 1,6-bisphosphatase 1 (FBP1) disrupts liver metabolic homeostasis and promotes tumour progression. FBP1 is universally ... Read more >>

Nat. Cell Biol. (Nature cell biology)
[2020, 22(6):728-739]

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Cervicovaginal fluid proteomic analysis to identify potential biomarkers for preterm birth.

Samuel Parry, Rita Leite, M Sean Esplin, Radek Bukowski, Heping Zhang, Michael Varner, William W Andrews, George R Saade, John Ilekis, Uma M Reddy, Hao Huang, Yoel Sadovsky, Ian A Blair, Joseph Biggio, ,

BACKGROUND:Spontaneous preterm birth is a leading cause of neonatal morbidity and mortality. Early identification of at-risk women by reliable screening tests could reduce the spontaneous preterm birth rate, but conventional methods such as obstetrical history and maternal cervical length screening identify only a minority of spontaneous preterm birth cases. Cervicovaginal ... Read more >>

Am. J. Obstet. Gynecol. (American journal of obstetrics and gynecology)
[2020, 222(5):493.e1-493.e13]

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Correction to "Role of Human Aldo-Keto Reductases in the Metabolic Activation of the Carcinogenic Air Pollutant 3-Nitrobenzanthrone".

Jessica R Murray, Clementina A Mesaros, Volker M Arlt, Albrecht Seidel, Ian A Blair, Trevor M Penning,

Chem. Res. Toxicol. (Chemical research in toxicology)
[2019, 32(11):2365]

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Voriconazole enhances UV-induced DNA damage by inhibiting catalase and promoting oxidative stress.

Vivian Lee, Michael D Gober, Hasan Bashir, Conor O'Day, Ian A Blair, Clementina Mesaros, Liwei Weng, Andrew Huang, Aaron Chen, Rachel Tang, Vince Anagnos, JiLon Li, Sophie Roling, Emilija Sagaityte, Andrew Wang, Chenyan Lin, Christopher Yeh, Cem Atillasoy, Christine Marshall, Tzvete Dentchev, Todd Ridky, John T Seykora,

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and is associated with cumulative UV exposure. Studies have shown that prolonged voriconazole use promotes cSCC formation; however, the biological mechanisms responsible for the increased incidence remain unclear. Here, we show that voriconazole directly increases oxidative ... Read more >>

Exp. Dermatol. (Experimental dermatology)
[2020, 29(1):29-38]

Cited: 1 time

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In Vitro Biotransformation of the Nrf2 Activator Bardoxolone: Formation of an Epoxide Metabolite That Undergoes Two Novel Glutathione-Mediated Metabolic Pathways: Epoxide Reduction and Oxidative Elimination of Nitrile Moiety.

Amin M Kamel, Stephen Bowlin, Ban Anwar, Holly Reichard, Joe Argus, Ian A Blair,

Metabolism of bardoxolone methyl (BARD-Me), an oleanolic acid derivative, and its epoxide metabolite was studied in different in vitro systems. BARD-Me also undergoes glutathione (GSH)-adduct formation via direct nucleophilic attack at the β-carbon of the α,β-unsaturated ketone substituent on the A-ring. The presence of an electron-withdrawing nitrile residue on the ... Read more >>

Chem. Res. Toxicol. (Chemical research in toxicology)
[2019, 32(11):2268-2280]

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The proteome and its dynamics: A missing piece for integrative multi-omics in schizophrenia.

Karin E Borgmann-Winter, Kai Wang, Sabyasachi Bandyopadhyay, Abolfazl Doostparast Torshizi, Ian A Blair, Chang-Gyu Hahn,

The complex and heterogeneous pathophysiology of schizophrenia can be deconstructed by integration of large-scale datasets encompassing genes through behavioral phenotypes. Genome-wide datasets are now available for genetic, epigenetic and transcriptomic variations in schizophrenia, which are then analyzed by newly devised systems biology algorithms. A missing piece, however, is the inclusion ... Read more >>

Schizophr. Res. (Schizophrenia research)
[2020, 217:148-161]

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Evaluation of antibodies for western blot analysis of frataxin protein isoforms.

Liwei Weng, Qingqing Wang, Sixiang Yu, Xiaolu Yang, David R Lynch, Clementina Mesaros, Ian A Blair,

Frataxin is the protein that is down-regulated in Friedreich ataxia (FRDA), an autosomal recessive genetic disease caused by an intronic GAA repeat expansion in intron-1 of the FXN gene. The GAA repeats result in epigenetic silencing of the FXN gene and reduced expression of the cytosolic full-length frataxin (1-210) protein. ... Read more >>

J. Immunol. Methods (Journal of immunological methods)
[2019, 474:112629]

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The current state of biomarker research for Friedreich's ataxia: a report from the 2018 FARA biomarker meeting.

Ian A Blair, Jennifer Farmer, Steven Hersch, Jane Larkindale, David R Lynch, Jill Napierala, Marek Napierala, R Mark Payne, Sub H Subramony,

The 2018 FARA Biomarker Meeting highlighted the current state of development of biomarkers for Friedreich's ataxia. A mass spectroscopy assay to sensitively measure mature frataxin (reduction of which is the root cause of disease) is being developed. Biomarkers to monitor neurological disease progression include imaging, electrophysiological measures and measures of ... Read more >>

Future Sci OA (Future science OA)
[2019, 5(6):FSO398]

Cited: 2 times

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Metabolic Detection of Bruton's Tyrosine Kinase Inhibition in Mantle Cell Lymphoma Cells.

Seung-Cheol Lee, Alexander A Shestov, Lili Guo, Qian Zhang, Jeffrey C Roman, Xiaobin Liu, Hong Y Wang, Stephen Pickup, Kavindra Nath, Pin Lu, Samuel Hofbauer, Clementina Mesaros, Y Lynn Wang, David S Nelson, Stephen J Schuster, Ian A Blair, Jerry D Glickson, Mariusz A Wasik,

Current methods to evaluate effects of kinase inhibitors in cancer are suboptimal. Analysis of changes in cancer metabolism in response to the inhibitors creates an opportunity for better understanding of the interplay between cell signaling and metabolism and, from the translational perspective, potential early evaluation of response to the inhibitors ... Read more >>

Mol. Cancer Res. (Molecular cancer research : MCR)
[2019, 17(6):1365-1377]

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Correction to Liquid Chromatography-High Resolution Mass Spectrometry Analysis of Platelet Frataxin as a Protein Biomarker for the Rare Disease Friedreich's Ataxia.

Lili Guo, Qingqing Wang, Liwei Weng, Lauren A Hauser, Cassandra J Strawser, Agostinho G Rocha, Andrew Dancis, Clementina Mesaros, David R Lynch, Ian A Blair,

Anal. Chem. (Analytical chemistry)
[2019, 91(3):2560]

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Analytical Methods for Mass Spectrometry-Based Metabolomics Studies.

Siyu Wang, Ian A Blair, Clementina Mesaros,

The advancement of mass spectrometry-based analytical platform largely facilitates small-molecule metabolomics studies, which allows simultaneously analysis of a large number of metabolites from bio-samples and give a general picture of metabolic changes related to diseases or environmental alteration. Due to the large diversity of cellular metabolites, globally and precisely examining ... Read more >>

Adv. Exp. Med. Biol. (Advances in experimental medicine and biology)
[2019, 1140:635-647]

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Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome.

Nelly Mauras, Lournaris Torres-Santiago, Richard Santen, Veronica Mericq, Judith Ross, Gerardo Colon-Otero, Ligeia Damaso, Jobayer Hossain, Qingqing Wang, Clementina Mesaros, Ian A Blair,

OBJECTIVE:The established link between oestrogen and breast cancer occurs via both oestrogen receptor (ER)-mediated and non ER-mediated mechanisms. The term genotoxic estrogens describes mutagenic metabolites, including oestrogen catechols and quinones, which have been linked to breast carcinogenesis in post-menopausal women. We aimed to assess whether the route of administration of ... Read more >>

Clin. Endocrinol. (Oxf) (Clinical endocrinology)
[2019, 90(1):155-161]

Cited: 1 time

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Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia.

David R Lynch, Jennifer Farmer, Lauren Hauser, Ian A Blair, Qing Qing Wang, Clementina Mesaros, Nathaniel Snyder, Sylvia Boesch, Melanie Chin, Martin B Delatycki, Paola Giunti, Angela Goldsberry, Chad Hoyle, Michael G McBride, Wolfgang Nachbauer, Megan O'Grady, Susan Perlman, S H Subramony, George R Wilmot, Theresa Zesiewicz, Colin Meyer,

Objective:Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and ... Read more >>

Ann Clin Transl Neurol (Annals of clinical and translational neurology)
[2019, 6(1):15-26]

Cited: 10 times

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Effect of Differences in Metabolic Activity of Melanoma Models on Response to Lonidamine plus Doxorubicin.

Kavindra Nath, Jeffrey Roman, David S Nelson, Lili Guo, Seung-Cheol Lee, Stepan Orlovskiy, Kevin Muriuki, Daniel F Heitjan, Stephen Pickup, Dennis B Leeper, Ian A Blair, Mary E Putt, Jerry D Glickson,

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):14654]

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Gestational Diabetes Alters the Metabolomic Profile in 2nd Trimester Amniotic Fluid in a Sex-Specific Manner.

Kathleen O'Neill, Jacqueline Alexander, Rikka Azuma, Rui Xiao, Nathaniel W Snyder, Clementina A Mesaros, Ian A Blair, Sara E Pinney,

Maternal diabetes and obesity induce marked abnormalities in glucose homeostasis and insulin secretion in the fetus, and are linked to obesity, diabetes, and metabolic disease in the offspring, with specific metabolic characterization based on offspring sex. Gestational diabetes (GDM) has profound effects on the intrauterine milieu, which may reflect and/or ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2018, 19(9):]

Cited: 6 times

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Associations between improvement in genitourinary symptoms of menopause and changes in the vaginal ecosystem.

Caroline M Mitchell, Sujatha Srinivasan, Anna Plantinga, Michael C Wu, Susan D Reed, Katherine A Guthrie, Andrea Z LaCroix, Tina Fiedler, Matthew Munch, Congzhou Liu, Noah G Hoffman, Ian A Blair, Katherine Newton, Ellen W Freeman, Hadine Joffe, Lee Cohen, David N Fredricks,

OBJECTIVE:The aim of the study was to identify associations between improvement in genitourinary symptoms of menopause (GSM) and vaginal microbiota, vaginal glycogen, and serum estrogen. METHODS:Thirty postmenopausal women enrolled in a hot flash treatment trial (oral estradiol vs venlafaxine vs placebo) who reported GSM and provided vaginal swabs at 0, ... Read more >>

Menopause (Menopause (New York, N.Y.))
[2018, 25(5):500-507]

Cited: 2 times

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Arginase 2 Suppresses Renal Carcinoma Progression via Biosynthetic Cofactor Pyridoxal Phosphate Depletion and Increased Polyamine Toxicity.

Joshua D Ochocki, Sanika Khare, Markus Hess, Daniel Ackerman, Bo Qiu, Jennie I Daisak, Andrew J Worth, Nan Lin, Pearl Lee, Hong Xie, Bo Li, Bradley Wubbenhorst, Tobi G Maguire, Katherine L Nathanson, James C Alwine, Ian A Blair, Itzhak Nissim, Brian Keith, M Celeste Simon,

Kidney cancer, one of the ten most prevalent malignancies in the world, has exhibited increased incidence over the last decade. The most common subtype is "clear cell" renal cell carcinoma (ccRCC), which features consistent metabolic abnormalities, such as highly elevated glycogen and lipid deposition. By integrating metabolomics, genomic, and transcriptomic ... Read more >>

Cell Metab. (Cell metabolism)
[2018, 27(6):1263-1280.e6]

Cited: 14 times

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The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations.

Roddy S O'Connor, Lili Guo, Saba Ghassemi, Nathaniel W Snyder, Andrew J Worth, Liwei Weng, Yoonseok Kam, Benjamin Philipson, Sophie Trefely, Selene Nunez-Cruz, Ian A Blair, Carl H June, Michael C Milone,

Etomoxir (ETO) is a widely used small-molecule inhibitor of fatty acid oxidation (FAO) through its irreversible inhibitory effects on the carnitine palmitoyl-transferase 1a (CPT1a). We used this compound to evaluate the role of fatty acid oxidation in rapidly proliferating T cells following costimulation through the CD28 receptor. We show that ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):6289]

Cited: 13 times

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Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen.

Wei Yue, Jiping Wang, Kristen A Atkins, Lisa Bottalico, Clementina Mesaros, Ian A Blair, Richard J Santen,

The Women's Health Initiative studies reported that the menopausal hormone therapy (MHT) regimen containing conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased, whereas CEE alone reduced breast cancer incidence. These observations suggest the possibility that CEE might exert unique actions on breast and also suggest the need to eliminate the ... Read more >>

Int. J. Cancer (International journal of cancer)
[2018, 143(5):1259-1268]

Cited: 1 time

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Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments.

Christopher Ecker, Lili Guo, Stefana Voicu, Luis Gil-de-Gómez, Andrew Medvec, Luis Cortina, Jackie Pajda, Melanie Andolina, Maria Torres-Castillo, Jennifer L Donato, Sarya Mansour, Evan R Zynda, Pei-Yi Lin, Angel Varela-Rohena, Ian A Blair, James L Riley,

T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ) production in a nutrient-poor environment. Unlike naive (TN) or central memory T ... Read more >>

Cell Rep (Cell reports)
[2018, 23(3):741-755]

Cited: 2 times

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Bioorthogonal pro-metabolites for profiling short chain fatty acylation.

Wilson R Sinclair, Jonathan H Shrimp, Thomas T Zengeya, Rhushikesh A Kulkarni, Julie M Garlick, Hans Luecke, Andrew J Worth, Ian A Blair, Nathaniel W Snyder, Jordan L Meier,

Short chain fatty acids (SCFAs) play a central role in health and disease. One function of these signaling molecules is to serve as precursors for short chain fatty acylation, a class of metabolically-derived posttranslational modifications (PTMs) that are established by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Via this mechanism, ... Read more >>

Chem Sci (Chemical science)
[2018, 9(5):1236-1241]

Cited: 0 times

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Defining Metabolic and Nonmetabolic Regulation of Histone Acetylation by NSAID Chemotypes.

Jonathan H Shrimp, Julie M Garlick, Tugsan Tezil, Alexander W Sorum, Andrew J Worth, Ian A Blair, Eric Verdin, Nathaniel W Snyder, Jordan L Meier,

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known for their effects on inflammatory gene expression. Although NSAIDs are known to impact multiple cellular signaling mechanisms, a recent finding is that the NSAID salicylate can disrupt histone acetylation, in part through direct inhibition of the lysine acetyltransferase (KAT) p300/CBP. While salicylate is a ... Read more >>

Mol. Pharm. (Molecular pharmaceutics)
[2018, 15(3):729-736]

Cited: 0 times

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On meta- and mega-analyses for gene-environment interactions.

Jing Huang, Yulun Liu, Steve Vitale, Trevor M Penning, Alexander S Whitehead, Ian A Blair, Anil Vachani, Margie L Clapper, Joshua E Muscat, Philip Lazarus, Paul Scheet, Jason H Moore, Yong Chen,

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, ... Read more >>

Genet. Epidemiol. (Genetic epidemiology)
[2017, 41(8):876-886]

Cited: 0 times

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