Leander Blaas

Karolinska Institutet | KI · Department of Biosciences and Nutrition

Epithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we show that Laminin α5 (Lama5) expression specifically in the luminal epithelial cells is necessary for normal mammary gland growth during puberty, and for alveologenesis during pregnan...

Epithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we demonstrate that expression of distinct laminin α-isoforms by luminal and basal mammary epithelial cells enforces lineage identity that is necessary for normal mammary gland growth an...

Genetically-engineered mouse models (GEMMs) lacking diseased-associated gene(s) globally or in a tissue-specific manner represent an attractive tool with which to assess the efficacy and toxicity of targeted pharmacological inhibitors. Stat3 and Stat5a/b transcription factors have been implicated in several pathophysiological conditions, and pharma...

Myc transcript levels in wild-type and mutant mice in Figure 1b-c.DOI: http://dx.doi.org/10.7554/eLife.23382.004

Myc transcript levels in MycΔ2-540/Δ2-540 mice relative to the wild-types in Figure 3a.DOI: http://dx.doi.org/10.7554/eLife.23382.010

Survival time and intestinal polyp numbers for mice in Figure 6a-b.DOI: http://dx.doi.org/10.7554/eLife.23382.016

B cell numbers in the wild-type and MycΔ2-540/Δ2-540 mice in Figure 2d.DOI: http://dx.doi.org/10.7554/eLife.23382.006

B and T-cell populations in the wild-type and MycΔ2-540/Δ2-540 mice in Figure 2—figure supplement 1a.DOI: http://dx.doi.org/10.7554/eLife.23382.008

List of genes that show significant differential expression in the wild-type and the Myc△2–540/△2–540 colon (q-value <0.05). DOI: http://dx.doi.org/10.7554/eLife.23382.018

List of primers and guide RNA sequences used in this study. DOI: http://dx.doi.org/10.7554/eLife.23382.019

The gene desert upstream of theMYConcogene on chromosome 8q24 contains susceptibility loci for several major forms of human cancer. The region shows high conservation between human and mouse and contains multipleMYCenhancers that are activated in tumor cells. However, the role of this region in normal development has not been addressed. Here we sho...

The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartme...

The gene desert upstream of the Myc oncogene on chromosome 8q24 contains susceptibility loci for several major forms of human cancer, including cancers of breast, prostate, and colon. The region shows high conservation between human and mouse and contains multiple MYC enhancers that are activated in tumor cells. However, the role of this region in...

Nature Communications 7:12321 doi: 10.1038/ncomms12321 (2016); Published 5 Aug 2016; Updated 13 Sep 2016 In Fig. 6f of this Article, the labelling of the two immunohistochemistry images was inadvertently changed from ‘Haematoxylin, ki67’ to ‘Haematoxylin, Casp-3’ during the production process.

A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of co...

μUS of a Ptch1ΔCol1 mouse prior to Tamoxifen administration Ultrasound (US) of a murine abdomen scanned from the anus rostral to the level of the liver. Note that this scan was performed by moving the US probe manually over the abdomen rather than using a 3D motor. The colonic lumen was gently inflated with US gel (peristaltic waves lead to variati...

Supplementary Figures 1-9 and Supplementary Tables 1-6.

μUS of a Ptch1Col1 mouse after Tamoxifen administration The same mouse seen in Supplementary video 1, scanned 3 weeks after the first scan. Note that the tumours are not discernable in this scan, using the kidney (from approximately frame 200) or liver tissue (from frame 535 onwards) as landmarks. Further scans revealed that the third tumour was st...

STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice r...

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Liver fibrosis is defined as the pathological excessive deposition of extracellular matrix proteins which contributes to a disruption of normal liver architecture. Fibrosis can progress to cirrhosis, which can eventually result in hepatocellular carcinoma. Over the past decades...

Unlabelled: Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking...

We here establish a mouse cancer model called Multi-Hit that allows for the evaluation of oncogene cooperativities in tumor development. The model is based on the stochastic expression of oncogene combinations ('hits') that are mediated by Cre in a given tissue. Cells with cooperating hits are positively selected and give rise to tumors. We used th...

The choice of an expression vector is a critical step in the field of recombinant protein production in mammalian cells lines. Most expression vectors used in the field are sensitive to the surrounding chromatin to their integration site into the host genome cell. This so-called chromatin positional effects influences the expression levels of the t...

Growth hormone (GH)-activated signal transducer and activator of transcription 5 (STAT5) and the glucocorticoid (GC)-responsive glucocorticoid receptor (GR) are important signal integrators in the liver during metabolic and physiologic stress. Their deregulation has been implicated in the development of metabolic liver diseases, such as steatosis a...

Chronic liver injury, liver fibrosis and formation of hepatocellular carcinoma are intimately linked and represent a major medical challenge since treatment options are limited. Therefore, it is important to identify cellular and molecular pathways that promote liver damage or provide hepatoprotection for development of therapeutic approaches. Rece...

Here we describe the generation of an inducible Cre transgenic line allowing conditional mutagenesis in ovarian granulosa cells. We have expressed the tamoxifen inducible CreER(T)² fusion protein from a Bacterial Artificial Chromosome (BAC) containing the regulatory elements of the hydroxysteroid (17-beta) dehydrogenase 1 (Hsd17b1) gene. Hsd17b1-iC...

Unlabelled: Growth hormone (GH) resistance and low serum levels of insulinlike growth factor 1 (IGF-1) are common features in human liver fibrosis and cirrhosis. Signal transducer and activator of transcription 5 (STAT5) controls several vital functions in the liver, including GH-mediated transcription of IGF-1. To investigate the role of STAT5 in...

BACKGROUND & AIMS: Signal transducer and activa-tor of transcription 3 (Stat3) is the main mediator of interleukin-6 –type cytokine signaling required for hepa-tocyte proliferation and hepatoprotection, but its role in sclerosing cholangitis and other cholestatic liver diseases remains unresolved. METHODS: We investigated the role of Stat3 in infla...

Signal transducer and activator of transcription 3 (Stat3) is the main mediator of interleukin-6-type cytokine signaling required for hepatocyte proliferation and hepatoprotection, but its role in sclerosing cholangitis and other cholestatic liver diseases remains unresolved. We investigated the role of Stat3 in inflammation-induced cholestatic liv...

s: First AACR International Conference on Frontiers in Basic Cancer Research--Oct 8–11, 2009; Boston MA The transcription factor Stat3 has been considered to promote progression and metastasis of intestinal cancers. We investigated the role of Stat3 in intestinal tumors using mice with conditional ablation of Stat3 in intestinal epithelial cells (...

The transcription factor signal transducer and activator of transcription 3 (Stat3) has been considered to promote progression and metastasis of intestinal cancers. We investigated the role of Stat3 in intestinal tumors using mice with conditional ablation of Stat3 in intestinal epithelial cells (Stat3(DeltaIEC)). In the Apc(Min) mouse model of int...

The development of appropriate expression vectors for large scale protein production constitutes a critical step in recombinant protein production. The use of conventional expression vectors to obtain cell lines is a cumbersome procedure. Often, stable cell lines produce low protein yields and production is not stable over the time. These problems...

The use of bacterial artificial chromosomes (BACs) modified via homologous recombination in Escherichia coli has become a powerful tool in the transgenic field. Homologous recombination allows the manipulation of BACs in very different ways. However this process can be cumbersome and problematic when using large targeting constructs containing seve...

Hedgehog (HH)/GLI signaling plays a critical role in epidermal development and basal cell carcinoma. Here, we provide evidence that epidermal growth factor receptor (EGFR) signaling modulates the target gene expression profile of GLI transcription factors in epidermal cells. Using expression profiling and quantitative reverse transcriptase PCR, we...