Amy L. Stiegler
Yale University
Publications 21
#1Luca Zammataro (Yale University)H-Index: 16
#2Salvatore Lopez (Yale University)H-Index: 13
Last.Chanhee Han (Yale University)H-Index: 3
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The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs)...
#1Andreas Brodehl (Libin Cardiovascular Institute of Alberta)H-Index: 8
#2Saman Rezazadeh (Libin Cardiovascular Institute of Alberta)H-Index: 1
Last.Amy L. Stiegler (Yale University)H-Index: 10
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Arrhythmogenic cardiomyopathy is a genetic heart muscle disorder characterized by fibro-fatty replacement of cardiomyocytes leading to life-threatening ventricular arrhythmias, heart failure, and sudden cardiac death. Mutations in genes encoding cardiac junctional proteins are known to cause about half of cases, while remaining genetic causes are unknown. Using exome sequencing, we identified 2 missense variants (p.H33N and p.H77Y) that were predicted to be damaging in the integrin-linked kinase...
#1Amy L. Stiegler (Yale University)H-Index: 10
#2Titus J. Boggon (Yale University)H-Index: 37
Pseudoenzymes generally lack detectable catalytic activity despite adopting the overall protein fold of their catalytically competent counterparts, indeed ‘pseudo’ family members seem to be incorporated in all enzyme classes. The small GTPase enzymes are important signaling proteins, and recent studies have identified many new family members with noncanonical residues within the catalytic cleft, termed pseudoGTPases. To illustrate recent discoveries in the field, we use the p190RhoGAP proteins a...
#1Amy L. Stiegler (Yale University)H-Index: 10
#2Titus J. Boggon (Yale University)H-Index: 37
Summary The pseudoGTPases are a rapidly growing and important group of pseudoenzymes. p190RhoGAP proteins are critical regulators of Rho signaling and contain two previously identified pseudoGTPase domains. Here we report that p190RhoGAP proteins contain a third pseudoGTPase domain, termed N-GTPase. We find that GTP constitutively purifies with the N-GTPase domain, and a 2.8-A crystal structure of p190RhoGAP-A co-purified with GTP reveals an unusual GTP-Mg 2+ binding pocket. Six inserts in N-GTP...
#1Amy L. Stiegler (Yale University)H-Index: 10
#2Titus J. Boggon (Yale University)H-Index: 37
The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the ‘middle domain’, previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support d...
#1Siming Zhao (Yale University)H-Index: 4
#2Stefania Bellone (Yale University)H-Index: 24
Last.Luca Zammataro L (Yale University)H-Index: 15
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Abstract Carcinosarcomas (CSs) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. We analyzed the mutational landscape of 68 uterine and ovarian CSs by whole-exome sequencing. We also performed multiregion whole-exome sequencing comprising two carcinoma and sarcoma samples from six tumors to resolve their evolutionary histories. The results demonstrated that carcinomatous and sarcomatous elements derive from a common precursor having m...
#1Silvia Vilarinho (Yale University)H-Index: 10
#2Sinan Sari (Gazi University)H-Index: 14
Last.Richard P. Lifton (Yale University)H-Index: 100
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Despite advances in the diagnosis and management of idiopathic noncirrhotic portal hypertension, its pathogenesis remains elusive. Insight may be gained from study of early-onset familial idiopathic noncirrhotic portal hypertension, in which Mendelian mutations may account for disease. We performed exome sequencing of eight subjects from six kindreds with onset of portal hypertension of indeterminate etiology during infancy or childhood. Three subjects from two consanguineous families shared the...