Magdalena Oroń

Magdalena Oroń
Mossakowski Medical Research Centre Polish Academy of Sciences · Laboratory of Human Disease Multi-omics

PhD

About

21
Publications
2,170
Reads
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165
Citations
Citations since 2017
20 Research Items
165 Citations
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Introduction
My research interest is a cancer cell biology. My PhD project was focused on the regilation of alternative splicing regulation by mutant p53 in breast cancer. Currently I'm working on the role of ubiquitin-proteasome system in tumor proteom regulation. In my work I apply many basic molecular biology techniques, different methods to analyse protein-protein and protein-RNA interations and confocal microscopy. I'm also familiar with Zebrafish model organism and its applications in cancer research.

Publications

Publications (21)
Article
Full-text available
The development of RNA sequencing methods has allowed us to study and better understand the landscape of aberrant pre-mRNA splicing in tumors. Altered splicing patterns are observed in many different tumors and affect all hallmarks of cancer: growth signal independence, avoidance of apoptosis, unlimited proliferation, invasiveness, angiogenesis, an...
Article
Full-text available
Proteasome machinery is a major proteostasis control system in human cells, actively compensated upon its inhibition. To understand this compensation, we compared global protein landscapes upon the proteasome inhibition with carfilzomib, in normal fibroblasts, cells of multiple myeloma, and cancers of lung, colon, and pancreas. Molecular chaperones...
Preprint
Human neoplasias are often addicted to the proteasome machinery. However, cancers have evolved efficient response mechanisms to overcome proteasome inhibition with bortezomib and carfilzomib - drugs approved for multiple myeloma treatment. To understand these responses we investigated proteome changes upon the proteasome inhibition with carfilzomib...
Article
Full-text available
The knowledge accumulating on the occurrence and mechanisms of the activation of oncogenes in human neoplasia necessitates an increasingly detailed understanding of their systemic interactions. None of the known oncogenic drivers work in isolation from the other oncogenic pathways. The cooperation between these pathways is an indispensable element...
Article
Full-text available
Gain-of-function (GOF) mutations in the TP53 gene lead to acquisition of new functions by the mutated tumor suppressor p53 protein. A number of the over-represented 'hot spot' mutations, including the ones in codons 175, 248 or 273, convey GOF phenotypes. Such phenotypes may include resistance to chemotherapeutics or changes in motility and invasiv...
Article
Full-text available
Human p53 protein acts as a transcription factor predominantly in a tetrameric form. Single residue changes, caused by hot-spot mutations of the TP53 gene in human cancer, transform wild-type (wt) p53 tumor suppressor proteins into potent oncoproteins - with gain-of-function, tumor-promoting activity. Oligomerization of p53 allows for a direct inte...
Article
Full-text available
Background: As crucial regulators of the immune response against pathogens, macrophages have been extensively shown also to be important players in several diseases, including cancer. Specifically, breast cancer macrophages tightly control the angiogenic switch and progression to malignancy. ID4, a member of the ID (inhibitors of differentiation)...
Article
Full-text available
The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this s...
Article
Full-text available
Despite decades of cancer research, the search for key oncogenesis regulators as potential targets for novel therapies continues. Proteins, belonging to ID family, may be such promising candidates. They are DNA binding inhibitors, mainly of the bHLH transcription factor subfamily, which regulate genes related to cell differentiation. ID genes are n...

Questions

Question (1)
Question
I performed CRISPR-KO of p53 in fibroblasts. I've got cells that lost the activity of WTp53 (several target genes tested on qPCR) but on western blot, I see still quite a high level of a protein that is slightly lower than WTp53, and is not inducible by nutlin. Any idea how to get rid of these remainings?
The other thing is CRISPR-HDR to introduce gain of function mutations e.g. R175h and R273H. Do you have any advice how to increase the efficiency?

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