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Author Joseph M Miano

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CRISPR-Mediated Single Nucleotide Polymorphism Modeling in Rats Reveals Insight Into Reduced Cardiovascular Risk Associated With Mediterranean G6PD Variant.

Atsushi Kitagawa, Igor Kizub, Christina Jacob, Kevin Michael, Angelo D'Alessandro, Julie A Reisz, Michael Grzybowski, Aron M Geurts, Petra Rocic, Rakhee Gupte, Joseph M Miano, Sachin A Gupte,

Epidemiological studies suggest that individuals in the Mediterranean region with a loss-of-function, nonsynonymous single nucleotide polymorphism (S188F), in glucose-6-phosphate dehydrogenase (G6pd) are less susceptible to vascular diseases. However, this association has not yet been experimentally proven. Here, we set out to determine whether the Mediterranean mutation confers protection from vascular ... Read more >>

Hypertension (Hypertension (Dallas, Tex. : 1979))
[2020, 76(2):523-532]

Cited: 0 times

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Coronary Disease-Associated Gene TCF21 Inhibits Smooth Muscle Cell Differentiation by Blocking the Myocardin-Serum Response Factor Pathway.

Manabu Nagao, Qing Lyu, Quanyi Zhao, Robert C Wirka, Joetsaroop Bagga, Trieu Nguyen, Paul Cheng, Juyong Brian Kim, Milos Pjanic, Joseph M Miano, Thomas Quertermous,

RATIONALE:The gene encoding TCF21 (transcription factor 21) has been linked to coronary artery disease risk by human genome-wide association studies in multiple racial ethnic groups. In murine models, Tcf21 is required for phenotypic modulation of smooth muscle cells (SMCs) in atherosclerotic tissues and promotes a fibroblast phenotype in these cells. ... Read more >>

Circ Res (Circulation research)
[2020, 126(4):517-529]

Cited: 2 times

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Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation.

Channabasavaiah B Gurumurthy, Aidan R O'Brien, Rolen M Quadros, John Adams, Pilar Alcaide, Shinya Ayabe, Johnathan Ballard, Surinder K Batra, Marie-Claude Beauchamp, Kathleen A Becker, Guillaume Bernas, David Brough, Francisco Carrillo-Salinas, Wesley Chan, Hanying Chen, Ruby Dawson, Victoria DeMambro, Jinke D'Hont, Katharine M Dibb, James D Eudy, Lin Gan, Jing Gao, Amy Gonzales, Anyonya R Guntur, Huiping Guo, Donald W Harms, Anne Harrington, Kathryn E Hentges, Neil Humphreys, Shiho Imai, Hideshi Ishii, Mizuho Iwama, Eric Jonasch, Michelle Karolak, Bernard Keavney, Nay-Chi Khin, Masamitsu Konno, Yuko Kotani, Yayoi Kunihiro, Imayavaramban Lakshmanan, Catherine Larochelle, Catherine B Lawrence, Lin Li, Volkhard Lindner, Xian-De Liu, Gloria Lopez-Castejon, Andrew Loudon, Jenna Lowe, Loydie A Jerome-Majewska, Taiji Matsusaka, Hiromi Miura, Yoshiki Miyasaka, Benjamin Morpurgo, Katherine Motyl, Yo-Ichi Nabeshima, Koji Nakade, Toshiaki Nakashiba, Kenichi Nakashima, Yuichi Obata, Sanae Ogiwara, Mariette Ouellet, Leif Oxburgh, Sandra Piltz, Ilka Pinz, Moorthy P Ponnusamy, David Ray, Ronald J Redder, Clifford J Rosen, Nikki Ross, Mark T Ruhe, Larisa Ryzhova, Ane M Salvador, Sabrina Shameen Alam, Radislav Sedlacek, Karan Sharma, Chad Smith, Katrien Staes, Lora Starrs, Fumihiro Sugiyama, Satoru Takahashi, Tomohiro Tanaka, Andrew W Trafford, Yoshihiro Uno, Leen Vanhoutte, Frederique Vanrockeghem, Brandon J Willis, Christian S Wright, Yuko Yamauchi, Xin Yi, Kazuto Yoshimi, Xuesong Zhang, Yu Zhang, Masato Ohtsuka, Satyabrata Das, Daniel J Garry, Tino Hochepied, Paul Thomas, Jan Parker-Thornburg, Antony D Adamson, Atsushi Yoshiki, Jean-Francois Schmouth, Andrei Golovko, William R Thompson, K C Kent Lloyd, Joshua A Wood, Mitra Cowan, Tomoji Mashimo, Seiya Mizuno, Hao Zhu, Petr Kasparek, Lucy Liaw, Joseph M Miano, Gaetan Burgio,

BACKGROUND:CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides ... Read more >>

Genome Biol (Genome biology)
[2019, 20(1):171]

Cited: 3 times

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CRISPR links to long noncoding RNA function in mice: A practical approach.

Joseph M Miano, Xiaochun Long, Qing Lyu,

Next generation sequencing has uncovered a trove of short noncoding RNAs (e.g., microRNAs) and long noncoding RNAs (lncRNAs) that act as molecular rheostats in the control of diverse homeostatic processes. Meanwhile, the tsunamic emergence of clustered regularly interspaced short palindromic repeats (CRISPR) editing has transformed our influence over all DNA-carrying ... Read more >>

Vascul Pharmacol (Vascular pharmacology)
[2019, 114:1-12]

Cited: 1 time

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SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4.

Qing Lyu, Suowen Xu, Yuyan Lyu, Mihyun Choi, Christine K Christie, Orazio J Slivano, Arshad Rahman, Zheng-Gen Jin, Xiaochun Long, Yawei Xu, Joseph M Miano,

SENCR is a human-specific, vascular cell-enriched long-noncoding RNA (lncRNA) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR RNA are shown to be elevated in several differentiated human EC ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2019, 116(2):546-555]

Cited: 12 times

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CRISPR-tagging mice in aging research.

Joseph M Miano, Xiaochun Long,

Aging (Albany NY) (Aging)
[2018, 10(9):2226-2227]

Cited: 0 times

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CRISPR-Cas9-Mediated Epitope Tagging Provides Accurate and Versatile Assessment of Myocardin-Brief Report.

Qing Lyu, Vidhi Dhagia, Yu Han, Bing Guo, Mary E Wines-Samuelson, Christine K Christie, Qiangzong Yin, Orazio J Slivano, Paul Herring, Xiaochun Long, Sachin A Gupte, Joseph M Miano,

Objective- Unreliable antibodies often hinder the accurate detection of an endogenous protein, and this is particularly true for the cardiac and smooth muscle cofactor, MYOCD (myocardin). Accordingly, the mouse Myocd locus was targeted with 2 independent epitope tags for the unambiguous expression, localization, and activity of MYOCD protein. Approach and ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2018, 38(9):2184-2190]

Cited: 6 times

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Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function.

Bing Guo, Qing Lyu, Orazio J Slivano, Ronald Dirkx, Christine K Christie, Jan Czyzyk, Aram F Hezel, Ali G Gharavi, Eric M Small, Joseph M Miano,

Podocytes contain an intricate actin cytoskeleton that is essential for the specialized function of this cell type in renal filtration. Serum response factor (SRF) is a master transcription factor for the actin cytoskeleton, but the in vivo expression and function of SRF in podocytes are unknown. We found that SRF ... Read more >>

J Am Soc Nephrol (Journal of the American Society of Nephrology : JASN)
[2018, 29(2):416-422]

Cited: 4 times

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What Do We Really Think About Human Germline Genome Editing, and What Does It Mean for Medicine?

Kiran Musunuru, William R Lagor, Joseph M Miano,

Circ Cardiovasc Genet (Circulation. Cardiovascular genetics)
[2017, 10(5):]

Cited: 3 times

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Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice.

Danny Halim, Michael P Wilson, Daniel Oliver, Erwin Brosens, Joke B G M Verheij, Yu Han, Vivek Nanda, Qing Lyu, Michael Doukas, Hans Stoop, Rutger W W Brouwer, Wilfred F J van IJcken, Orazio J Slivano, Alan J Burns, Christine K Christie, Karen L de Mesy Bentley, Alice S Brooks, Dick Tibboel, Suowen Xu, Zheng Gen Jin, Tono Djuwantono, Wei Yan, Maria M Alves, Robert M W Hofstra, Joseph M Miano,

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2017, 114(13):E2739-E2747]

Cited: 20 times

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Testosterone Rescues the De-Differentiation of Smooth Muscle Cells Through Serum Response Factor/Myocardin.

Carolina Leimgruber, Amado A Quintar, Nahuel Peinetti, María V Scalerandi, Juan P Nicola, Joseph M Miano, Cristina A Maldonado,

Prostatic smooth muscle cells (pSMCs) differentiation is a key factor for prostatic homeostasis, with androgens exerting multiple effects on these cells. Here, we demonstrated that the myodifferentiator complex Srf/Myocd is up-regulated by testosterone in a dose-dependent manner in primary cultures of rat pSMCs, which was associated to the increase in ... Read more >>

J Cell Physiol (Journal of cellular physiology)
[2017, 232(10):2806-2817]

Cited: 3 times

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Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels.

Moon Young Lee, Chanjae Park, Se Eun Ha, Paul J Park, Robyn M Berent, Brian G Jorgensen, Robert D Corrigan, Nathan Grainger, Peter J Blair, Orazio J Slivano, Joseph M Miano, Sean M Ward, Terence K Smith, Kenton M Sanders, Seungil Ro,

Serum response factor (SRF) transcriptionally regulates expression of contractile genes in smooth muscle cells (SMC). Lack or decrease of SRF is directly linked to a phenotypic change of SMC, leading to hypomotility of smooth muscle in the gastrointestinal (GI) tract. However, the molecular mechanism behind SRF-induced hypomotility in GI smooth ... Read more >>

PLoS One (PloS one)
[2017, 12(2):e0171262]

Cited: 3 times

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Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.

Qiuyu Martin Zhu, Kyung Ae Ko, Sara Ture, Michael A Mastrangelo, Ming-Huei Chen, Andrew D Johnson, Christopher J O'Donnell, Craig N Morrell, Joseph M Miano, Charles J Lowenstein,

OBJECTIVE:To identify and characterize the effect of a SNP (single-nucleotide polymorphism) in the STXBP5 locus that is associated with altered thrombosis in humans. GWAS (genome-wide association studies) have identified numerous SNPs associated with human thrombotic phenotypes, but determining the functional significance of an individual candidate SNP can be challenging, particularly ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2017, 37(2):264-270]

Cited: 7 times

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Maternal deprivation alters expression of neural maturation gene tbr1 in the amygdala paralaminar nucleus in infant female macaques.

Danielle M de Campo, Judy L Cameron, Joseph M Miano, David A Lewis, Karoly Mirnics, Julie L Fudge,

Early parental loss is associated with social-emotional dysregulation and amygdala physiologic changes. Previously, we examined whole amygdala gene expression in infant monkeys exposed to early maternal deprivation. Here, we focus on an amygdala region with immature neurons at birth: the paralaminar nucleus (PL). We hypothesized that 1) the normal infant ... Read more >>

Dev Psychobiol (Developmental psychobiology)
[2017, 59(2):235-249]

Cited: 4 times

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Challenges and Opportunities in Linking Long Noncoding RNAs to Cardiovascular, Lung, and Blood Diseases.

Jane E Freedman, Joseph M Miano, ,

The new millennium heralds an unanticipated surge of genomic information, most notably an expansive class of long noncoding RNAs (lncRNAs). These transcripts, which now outnumber all protein-coding genes, often exhibit the same characteristics as mRNAs (RNA polymerase II-dependent, 5' methyl-capped, multiexonic, polyadenylated); yet, they do not encode for stable, well-conserved ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2017, 37(1):21-25]

Cited: 18 times

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MYOSLID Is a Novel Serum Response Factor-Dependent Long Noncoding RNA That Amplifies the Vascular Smooth Muscle Differentiation Program.

Jinjing Zhao, Wei Zhang, Mingyan Lin, Wen Wu, Pengtao Jiang, Emiley Tou, Min Xue, Angelene Richards, David Jourd'heuil, Arif Asif, Deyou Zheng, Harold A Singer, Joseph M Miano, Xiaochun Long,

OBJECTIVE:Long noncoding RNAs (lncRNA) represent a growing class of noncoding genes with diverse cellular functions. We previously reported on SENCR, an lncRNA that seems to support the vascular smooth muscle cell (VSMC) contractile phenotype. However, information about the VSMC-specific lncRNAs regulated by myocardin (MYOCD)/serum response factor, the master switch for ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2016, 36(10):2088-2099]

Cited: 36 times

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Vascular smooth muscle cell contractile protein expression is increased through protein kinase G-dependent and -independent pathways by glucose-6-phosphate dehydrogenase inhibition and deficiency.

Sukrutha Chettimada, Sachindra Raj Joshi, Vidhi Dhagia, Alessandro Aiezza, Thomas M Lincoln, Rakhee Gupte, Joseph M Miano, Sachin A Gupte,

Homeostatic control of vascular smooth muscle cell (VSMC) differentiation is critical for contractile activity and regulation of blood flow. Recently, we reported that precontracted blood vessels are relaxed and the phenotype of VSMC is regulated from a synthetic to contractile state by glucose-6-phosphate dehydrogenase (G6PD) inhibition. In the current study, ... Read more >>

Am J Physiol Heart Circ Physiol (American journal of physiology. Heart and circulatory physiology)
[2016, 311(4):H904-H912]

Cited: 3 times

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Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation.

Margaret D Ballantyne, Karine Pinel, Rachel Dakin, Alex T Vesey, Louise Diver, Ruth Mackenzie, Raquel Garcia, Paul Welsh, Naveed Sattar, Graham Hamilton, Nikhil Joshi, Marc R Dweck, Joseph M Miano, Martin W McBride, David E Newby, Robert A McDonald, Andrew H Baker,

BACKGROUND:Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs ... Read more >>

Circulation (Circulation)
[2016, 133(21):2050-2065]

Cited: 65 times

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A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research.

Joseph M Miano, Qiuyu Martin Zhu, Charles J Lowenstein,

Previous efforts to target the mouse genome for the addition, subtraction, or substitution of biologically informative sequences required complex vector design and a series of arduous steps only a handful of laboratories could master. The facile and inexpensive clustered regularly interspaced short palindromic repeats (CRISPR) method has now superseded traditional ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2016, 36(6):1058-1075]

Cited: 19 times

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Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle Development and Maintenance of Differentiated Phenotype.

Chanjae Park, Moon Young Lee, Paul J Park, Se Eun Ha, Robyn M Berent, Robert Fuchs, Joseph M Miano, Laren S Becker, Kenton M Sanders, Seungil Ro,

BACKGROUND/AIMS:Smooth muscle cells (SMCs) characteristically express serum response factor (SRF), which regulates their development. The role of SRF in SMC plasticity in the pathophysiological conditions of gastrointestinal (GI) tract is less characterized. METHODS:We generated SMC-specific Srf knockout mice and characterized the prenatally lethal phenotype using ultrasound biomicroscopy and histological analysis. ... Read more >>

J Neurogastroenterol Motil (Journal of neurogastroenterology and motility)
[2015, 21(4):589-602]

Cited: 5 times

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Smooth Muscle Cell Genome Browser: Enabling the Identification of Novel Serum Response Factor Target Genes.

Moon Young Lee, Chanjae Park, Robyn M Berent, Paul J Park, Robert Fuchs, Hannah Syn, Albert Chin, Jared Townsend, Craig C Benson, Doug Redelman, Tsai-Wei Shen, Jong Kun Park, Joseph M Miano, Kenton M Sanders, Seungil Ro,

Genome-scale expression data on the absolute numbers of gene isoforms offers essential clues in cellular functions and biological processes. Smooth muscle cells (SMCs) perform a unique contractile function through expression of specific genes controlled by serum response factor (SRF), a transcription factor that binds to DNA sites known as the ... Read more >>

PLoS One (PloS one)
[2015, 10(8):e0133751]

Cited: 17 times

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Myocardin Family Members Drive Formation of Caveolae.

Katarzyna K Krawczyk, Ingrid Yao Mattisson, Mari Ekman, Nikolay Oskolkov, Rebecka Grantinge, Dorota Kotowska, Björn Olde, Ola Hansson, Sebastian Albinsson, Joseph M Miano, Catarina Rippe, Karl Swärd,

Caveolae are membrane organelles that play roles in glucose and lipid metabolism and in vascular function. Formation of caveolae requires caveolins and cavins. The make-up of caveolae and their density is considered to reflect cell-specific transcriptional control mechanisms for caveolins and cavins, but knowledge regarding regulation of caveolae genes is ... Read more >>

PLoS One (PloS one)
[2015, 10(8):e0133931]

Cited: 14 times

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The short and long of noncoding sequences in the control of vascular cell phenotypes.

Joseph M Miano, Xiaochun Long,

The two principal cell types of importance for normal vessel wall physiology are smooth muscle cells and endothelial cells. Much progress has been made over the past 20 years in the discovery and function of transcription factors that coordinate proper differentiation of these cells and the maintenance of vascular homeostasis. More ... Read more >>

Cell Mol Life Sci (Cellular and molecular life sciences : CMLS)
[2015, 72(18):3457-3488]

Cited: 17 times

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Myocardin regulates vascular smooth muscle cell inflammatory activation and disease.

Matthew Ackers-Johnson, Amarnath Talasila, Andrew P Sage, Xiaochun Long, Ilze Bot, Nicholas W Morrell, Martin R Bennett, Joseph M Miano, Sanjay Sinha,

OBJECTIVE:Atherosclerosis, the cause of 50% of deaths in westernized societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local proinflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2015, 35(4):817-828]

Cited: 31 times

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CRISPR-Cas9 genome editing of a single regulatory element nearly abolishes target gene expression in mice--brief report.

Yu Han, Orazio J Slivano, Christine K Christie, Albert W Cheng, Joseph M Miano,

OBJECTIVE:To ascertain the importance of a single regulatory element in the control of Cnn1 expression using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genome editing. APPROACH AND RESULTS:The CRISPR/Cas9 system was used to produce 3 of 18 founder mice carrying point mutations in an intronic CArG box of ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2015, 35(2):312-315]

Cited: 30 times

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