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Institution

Kettering University

EducationFlint, Michigan, United States
About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: RNA & Antigen. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.
Topics: RNA, Antigen, DNA, Cancer, Population


Papers
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Journal ArticleDOI
TL;DR: Diet provides a further therapeutic strategy in active Crohn's disease and clinical improvement in the diet group was associated with significant changes in plasma albumin and alpha 1-antichymotrypsin concentrations and erythrocyte sedimentation rate.

198 citations

Journal ArticleDOI
20 Oct 2016-Nature
TL;DR: It is found that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically ‘rewired’ to form a network of stable, survival-facilitating, high-molecular-weight complexes.
Abstract: Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and folding enzymes-dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery. Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy. As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis. Such limitations have led to a bottleneck in our understanding of chaperome-related disease biology and in the development of chaperome-targeted cancer treatment. Here we examined the chaperome complexes in a large set of tumour specimens. The methods used maintained the endogenous native state of tumours and we exploited this to investigate the molecular characteristics and composition of the chaperome in cancer, the molecular factors that drive chaperome networks to crosstalk in tumours, the distinguishing factors of the chaperome in tumours sensitive to pharmacologic inhibition, and the characteristics of tumours that may benefit from chaperome therapy. We find that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically 'rewired' to form a network of stable, survival-facilitating, high-molecular-weight complexes. The chaperones heat shock protein 90 (HSP90) and heat shock cognate protein 70 (HSC70) are nucleating sites for these physically and functionally integrated complexes. The results indicate that these tightly integrated chaperome units, here termed the epichaperome, can function as a network to enhance cellular survival, irrespective of tissue of origin or genetic background. The epichaperome, present in over half of all cancers tested, has implications for diagnostics and also provides potential vulnerability as a target for drug intervention.

198 citations

Journal ArticleDOI
TL;DR: It is reported here that antisense transcription of the Hox miRNA locus mir-iab-4 generates the novel pre-miRNA hairpin mir- iab-8, which is then processed into endogenous mature miRNAs, which contribute to the functional diversification of miRNA genes.
Abstract: Many microRNA (miRNA) loci exhibit compelling hairpin structures on both sense and antisense strands; however, the possibility that a miRNA gene might produce functional species from its antisense strand has not been examined. We report here that antisense transcription of the Hox miRNA locus mir-iab-4 generates the novel pre-miRNA hairpin mir-iab-8, which is then processed into endogenous mature miRNAs. Sense and antisense iab-4/iab-8 miRNAs are functionally distinguished by their distinct domains of expression and targeting capabilities. We find that miR-iab-8-5p, like miR-iab-4-5p, is also relevant to Hox gene regulation. Ectopic mir-iab-8 can strongly repress the Hox genes Ultrabithorax and abdominal-A via extensive arrays of conserved target sites, and can induce a dramatic homeotic transformation of halteres into wings. We generalize the antisense miRNA principle by showing that several other loci in both invertebrates and vertebrates are endogenously processed on their antisense strands into mature miRNAs with distinct seeds. These findings demonstrate that antisense transcription and processing contributes to the functional diversification of miRNA genes.

197 citations

Journal ArticleDOI
TL;DR: Patients with common varied immunodeficiency have been observed for periods of 1–13 years, showing an 8- to 13-fold increase in cancer in general for patients who have this immunODeficiency and a 438-fold rise in lymphoma for females.
Abstract: Ninety-eight patients with common varied immunodeficiency have been observed for periods of 1–13 years. In 1986, 78 were alive, 19 had died, and 1 could not be located. Eleven patients in the group had developed cancer; two patients had had two cancers. Of the total number of neoplastic malignancies, seven were non-Hodgkin's lymphoma, one patient had a Waldenstrom's macroglobulinemia, and nine of the patients who developed cancer were female. Cancer developed in the fifth or sixth decade of life for 10 of the 11 patients. These data show an 8- to 13-fold increase in cancer in general for patients who have this immunodeficiency and a 438-fold increase in lymphoma for females.

197 citations

Journal ArticleDOI
TL;DR: The recognition of hundreds of mammalian mirtrons provides a new foundation for understanding the scope and evolutionary dynamics of Dicer substrates in mammals and provides the first Northern validation for mammalian mirTrons.
Abstract: Atypical miRNA substrates do not fit criteria often used to annotate canonical miRNAs, and can escape the notice of miRNA genefinders. Recent analyses expanded the catalogs of invertebrate splicing-derived miRNAs ("mirtrons"), but only a few tens of mammalian mirtrons have been recognized to date. We performed meta-analysis of 737 mouse and human small RNA data sets comprising 2.83 billion raw reads. Using strict and conservative criteria, we provide confident annotation for 237 mouse and 240 human splicing-derived miRNAs, the vast majority of which are novel genes. These comprise three classes of splicing-derived miRNAs in mammals: conventional mirtrons, 5'-tailed mirtrons, and 3'-tailed mirtrons. In addition, we segregated several hundred additional human and mouse loci with candidate (and often compelling) evidence. Most of these loci arose relatively recently in their respective lineages. Nevertheless, some members in each of the three mirtron classes are conserved, indicating their incorporation into beneficial regulatory networks. We also provide the first Northern validation for mammalian mirtrons, and demonstrate Dicer-dependent association of mature miRNAs from all three classes of mirtrons with Ago2. The recognition of hundreds of mammalian mirtrons provides a new foundation for understanding the scope and evolutionary dynamics of Dicer substrates in mammals.

196 citations


Authors

Showing all 6853 results

NameH-indexPapersCitations
Joan Massagué189408149951
Chris Sander178713233287
Timothy A. Springer167669122421
Murray F. Brennan16192597087
Charles M. Rice15456183812
Lloyd J. Old152775101377
Howard I. Scher151944101737
Paul Tempst14830989225
Pier Paolo Pandolfi14652988334
Barton F. Haynes14491179014
Jedd D. Wolchok140713123336
James P. Allison13748383336
Harold E. Varmus13749676320
Scott W. Lowe13439689376
David S. Klimstra13356461682
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20238
202216
2021211
2020234
2019204
2018225