Search

Your search keyword '"Helin, Kristian"' showing total 553 results
Start Over Author "Helin, Kristian" Language english
553 results on '"Helin, Kristian"'

2. Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization

Author

Kaito, Satoshi, Aoyama, Kazumasa, Oshima, Motohiko, Tsuchiya, Akiho, Miyota, Makiko, Yamashita, Masayuki, Koide, Shuhei, Nakajima-Takagi, Yaeko, Kozuka-Hata, Hiroko, Oyama, Masaaki, Yogo, Takao, Yabushita, Tomohiro, Ito, Ryoji, Ueno, Masaya, Hirao, Atsushi, Tohyama, Kaoru, Li, Chao, Kawabata, Kimihito Cojin, Yamaguchi, Kiyoshi, Furukawa, Yoichi, Kosako, Hidetaka, Yoshimi, Akihide, Goyama, Susumu, Nannya, Yasuhito, Ogawa, Seishi, Agger, Karl, Helin, Kristian, Yamazaki, Satoshi, Koseki, Haruhiko, Doki, Noriko, Harada, Yuka, Harada, Hironori, Nishiyama, Atsuya, Nakanishi, Makoto, and Iwama, Atsushi

Published
2024
Full Text
View/download PDF

8. The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes

Author

Trempenau, Mette Louise, Schuster, Mikkel Bruhn, Pundhir, Sachin, Pereira, Mafalda Araujo, Kalvisa, Adrija, Tapia, Marta, Su, Jinyu, Ge, Ying, de Boer, Bauke, Balhuizen, Alexander, Bagger, Frederik Otzen, Shliaha, Pavel, Sroczynska, Patrycja, Walfridsson, Julian, Grønbæk, Kirsten, Theilgaard-Mönch, Kim, Jensen, Ole N., Helin, Kristian, and Porse, Bo T.

Published
2023
Full Text
View/download PDF

19. Correction: Utx Is Required for Proper Induction of Ectoderm and Mesoderm during Differentiation of Embryonic Stem Cells.

Author

Torres, Cristina Morales, Laugesen, Anne, and Helin, Kristian

Subjects
MESODERM, EMBRYONIC stem cells, ECTODERM, GENE expression, GENETIC regulation
Abstract

This document is a correction notice for an article titled "Utx Is Required for Proper Induction of Ectoderm and Mesoderm during Differentiation of Embryonic Stem Cells." The authors address concerns about images in Figures 1, 5, 7, and S2 and provide additional information, corrected figures, and underlying data for these experiments. The authors apologize for the errors in the published article. The document also includes graphs and supporting information related to the study. [Extracted from the article]

Published
2024
Full Text
View/download PDF

23. RIO-kinase 2 is essential for hematopoiesis.

Author

Messling, Jan-Erik, Peña-Rømer, Isabel, Moroni, Ann Sophie, Bruestl, Sarah, and Helin, Kristian

Subjects
RIBOSOMES, HEMATOPOIESIS, HEMATOPOIETIC system, HEMATOPOIETIC stem cells, ORGANELLE formation, STEM cell factor, BONE marrow transplantation, GENETIC translation
Abstract

Regulation of protein synthesis is a key factor in hematopoietic stem cell maintenance and differentiation. Rio-kinase 2 (RIOK2) is a ribosome biogenesis factor that has recently been described an important regulator of human blood cell development. Additionally, we have previously identified RIOK2 as a regulator of protein synthesis and a potential target for the treatment of acute myeloid leukemia (AML). However, its functional relevance in several organ systems, including normal hematopoiesis, is not well understood. Here, we investigate the consequences of RIOK2 loss on normal hematopoiesis using two different conditional knockout mouse models. Using competitive and non-competitive bone marrow transplantations, we demonstrate that RIOK2 is essential for the differentiation of hematopoietic stem and progenitor cells (HSPCs) as well as for the maintenance of fully differentiated blood cells in vivo as well as in vitro. Loss of RIOK2 leads to rapid death in full-body knockout mice as well as mice with RIOK2 loss specific to the hematopoietic system. Taken together, our results indicate that regulation of protein synthesis and ribosome biogenesis by RIOK2 is essential for the function of the hematopoietic system. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

27. Identification of recurrent FHL2-GLI2 oncogenic fusion in sclerosing stromal tumors of the ovary

Author

Kim, Sarah H., Da Cruz Paula, Arnaud, Basili, Thais, Dopeso, Higinio, Bi, Rui, Pareja, Fresia, da Silva, Edaise M., Gularte-Mérida, Rodrigo, Sun, Zhen, Fujisawa, Sho, Smith, Caitlin G., Ferrando, Lorenzo, Martins Sebastião, Ana Paula, Bykov, Yonina, Li, Anqi, Silveira, Catarina, Ashley, Charles W., Stylianou, Anthe, Selenica, Pier, Samore, Wesley R., Jungbluth, Achim A., Zamarin, Dmitriy, Abu-Rustum, Nadeem R., Helin, Kristian, Soslow, Robert A., Reis-Filho, Jorge S., Oliva, Esther, and Weigelt, Britta

Published
2020
Full Text
View/download PDF

29. Discovery of NSD2‐Degraders from Novel and Selective DEL Hits.

Author

LegaardAndersson, Jan, Christensen, Jesper, Kleine‐Kohlbrecher, Daniela, Vacher Comet, Itys, Fullerton Støier, Jonatan, Antoku, Yasuko, Poljak, Visnja, Moretti, Loris, Dolberg, Johannes, Jacso, Tomas, Jensby Nielsen, Søren, Nørregaard‐Madsen, Mads, Franch, Thomas, Helin, Kristian, and Cloos, Paul A. C.

Published
2023
Full Text
View/download PDF

30. An alternative NURF complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions.

Author

Radzisheuskaya, Aliaksandra, Peña‐Rømer, Isabel, Lorenzini, Eugenia, Koche, Richard, Zhan, Yingqian, Shliaha, Pavel V, Cooper, Alexandra J, Fan, Zheng, Shlyueva, Daria, Johansen, Jens V, Hendrickson, Ronald C, and Helin, Kristian

Subjects
ACUTE myeloid leukemia, CELL survival, CELL growth, CRISPRS, CHROMATIN
Abstract

Efficient treatment of acute myeloid leukemia (AML) patients remains a challenge despite recent therapeutic advances. Here, using a CRISPRi screen targeting chromatin factors, we identified the nucleosome‐remodeling factor (NURF) subunit BPTF as an essential regulator of AML cell survival. We demonstrate that BPTF forms an alternative NURF chromatin remodeling complex with SMARCA5 and BAP18, which regulates the accessibility of a large set of insulator regions in leukemic cells. This ensures efficient CTCF binding and boundary formation between topologically associated domains that is essential for maintaining the leukemic transcriptional programs. We also demonstrate that the well‐studied PHD2‐BROMO chromatin reader domains of BPTF, while contributing to complex recruitment to chromatin, are dispensable for leukemic cell growth. Taken together, our results uncover how the alternative NURF complex contributes to leukemia and provide a rationale for its targeting in AML. Synopsis: Chromatin regulators play a crucial role in cancer, including acute myeloid leukemia (AML). Here, a screen for new vulnerabilities in MLL‐rearranged AML identifies an alternative NURF chromatin remodelling complex that maintains leukemic transcriptional programs. CRISPRi screen in AML cells identifies BPTF as an essential regulator of cell growth.BPTF interacts with SMARCA5 and BAP18 to form an alternative NURF complex in AML cells.The NURF complex controls insulator accessibility, CTCF binding, and TAD boundary formation.PHD2 and BROMO domains of BPTF are not required for leukemic cell growth. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

41. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies

Author

De Raedt, Thomas, Beert, Eline, Pasmant, Eric, Luscan, Armelle, Brems, Hilde, Ortonne, Nicolas, Helin, Kristian, Hornick, Jason L., Mautner, Victor, Kehrer-Sawatzki, Hildegard, Clapp, Wade, Bradner, James, Vidaud, Michel, Upadhyaya, Meena, Legius, Eric, and Cichowski, Karen

Subjects
Gliomas -- Analysis -- Research, Genetic transcription -- Analysis -- Research, Epigenetic inheritance -- Analysis -- Research, Ras genes -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The polycomb repressive complex 2 (PRC2) exerts oncogenic effects in many tumour types (1). However, loss-of-function mutations in PRC2 components occur in a subset of haematopoietic malignancies, suggesting that this complex plays a dichotomous and poorly understood role in cancer (2,3). Here we provide genomic, cellular, and mouse modelling data demonstrating that the polycomb group gene SUZ12 functions as tumour suppressor in PNS tumours, high-grade gliomas and melanomas by cooperating with mutations in NF1. NF1 encodes a Ras GTPase-activating protein (RasGAP) and its loss drives cancer by activating Ras (4).We show that SUZ12 loss potentiates the effects of NF1 mutations by amplifying Ras-driven transcription through effects on chromatin. Importantly, however, SUZ12inactivation also triggers an epigenetic switch that sensitizes these cancers to bromodomain inhibitors. Collectively, these studies not only reveal an unexpected connection between the PRC2 complex, NF1 and Ras, but also identify a promising epigenetic-based therapeutic strategy that may be exploited for a variety of cancers., The Ras pathway is commonly deregulated in cancer (5). Oncogenic RAS mutations occur in approximately 30% of tumours; however, mutations in upstream regulators and downstream effectors are also prevalent (5). [...]

Published
2014

42. FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS

Author

Liu, Yawei, Carlsson, Robert, Comabella, Manuel, Wang, JunYang, Kosicki, Michael, Carrion, Belinda, Hasan, Maruf, Wu, Xudong, Montalban, Xavier, Dziegiel, Morten Hanefeld, Sellebjerg, Finn, Sorensen, Per Soelberg, Helin, Kristian, and Issazadeh-Navikas, Shohreh

Subjects
T cells -- Analysis -- Physiological aspects -- Genetic aspects -- Research, Multiple sclerosis -- Development and progression -- Genetic aspects -- Research, Transcription factors -- Physiological aspects -- Research, Encephalomyelitis -- Development and progression -- Genetic aspects -- Research, Biological sciences, Health
Abstract

The defective generation or function of regulatory T ([T.sub.reg]) cells in autoimmune disease contributes to chronic inflammation and tissue injury. We report the identification of FoxA1 as a transcription factor in T cells that, after ectopic expression, confers suppressive properties in a newly identified [T.sub.reg] cell population, herein called [FoxA1.sup.+] [T.sub.reg] cells. FoxA1 bound to the Pdl1 promoter, inducing programmed cell death ligand 1 (Pd-l1) expression, which was essential for the [FoxA1.sup.+] [T.sub.reg] cells to kill activated T cells. [FoxA1.sup.+] [T.sub.reg] cells develop primarily in the central nervous system in response to autoimmune inflammation, have a distinct transcriptional profile and are CD4.+]FoxA1+CD47+CD69+PD-[L1.sup.hi][FoxP3.sup.?]. Adoptive transfer of stable [FoxA1.sup.+] [T.sub.reg] cells inhibited experimental autoimmune encephalomyelitis in a FoxA1-and Pd-l1-dependent manner. The development of [FoxA1.sup.+] [T.sub.reg] cells is induced by interferon-b (IFN-b) and requires T cell-intrinsic IFN-α/β receptor (Ifnar) signaling, as the frequency of [FoxA1.sup.+] [T.sub.reg] cells was reduced in [Ifnb.sup.?/?] and [Ifnar.sup.?/?] mice. In individuals with relapsing-remitting multiple sclerosis, clinical response to treatment with IFN-b was associated with an increased frequency of suppressive [FoxA1.sup.+] [T.sub.reg] cells in the blood. These findings suggest that FoxA1 is a lineage-specification factor that is induced by IFN-b and supports the differentiation and suppressive function of [FoxA1.sup.+] [T.sub.reg] cells., Immune function that preserves tolerance while retaining antimicro-bial function is imperative for preventing chronic inflammation and autoimmunity. [T.sub.reg] cell-mediated immune suppression is important for suppressing inflammatory responses, and defects in [...]

Published
2014
Full Text
View/download PDF

46. Chromatin proteins and modifications as drug targets

Author

Helin, Kristian and Dhanak, Dashyant

Subjects
Chromatin -- Physiological aspects, Post-translational modification -- Research, Histones -- Physiological aspects -- Genetic aspects, Epigenetic inheritance -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A plethora of groundbreaking studies have demonstrated the importance of chromatin-associated proteins and posttranslational modifications of histones, proteins and DNA (so-called epigenetic modifications) for transcriptional control and normal development. Disruption of epigenetic control is a frequent event in disease, and the first epigenetic based therapies for cancer treatment have been approved. A generation of new classes of potent and specific inhibitors for several chromatin-associated proteins have shown promise in preclinical trials. Although the biology of epigenetic regulation is complex, new inhibitors such as these will hopefully be of clinical use in the coming years., Epigenetics is defined as heritable traits that are not linked to changes in the DNA sequence; however, in broader terms, epigenetics is used to describe the mechanisms by which chromatinassociated [...]

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results