Klaudia Szymonowicz

Klaudia Szymonowicz
University of Texas MD Anderson Cancer Center | MD Anderson · Department of Experimental Radiation Oncology

PhD

About

30
Publications
3,348
Reads
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351
Citations

Publications

Publications (30)
Article
Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because of their loss of function. To uncover specific vulnerabilities for cells with deficiency in any given tumor suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel of isog...
Article
Full-text available
Cancer bioenergetics fuel processes necessary to maintain viability and growth under stress conditions. We hypothesized that cancer metabolism supports the repair of radiation-induced DNA double-strand breaks (DSBs). We combined the systematic collection of metabolic and radiobiological data from a panel of irradiated cancer cell lines with mathema...
Article
Full-text available
Because of essential roles of DNA damage response (DDR) in the maintenance of genomic integrity, cellular homeostasis, and tumor suppression, targeting DDR has become a promising therapeutic strategy for cancer treatment. However, the benefits of cancer therapy targeting DDR are limited mainly due to the lack of predictive biomarkers. To address th...
Conference Paper
p>Flexibility and reprogramming of cancer metabolism supports cancer progression and therapy resistance. In previous work we described opportunities for overcoming environment-induced resistance to ionizing radiation (IR) by pharmacologic inhibition of metabolic processes [1,2,3]. Here, we hypothesized that certain aspects of cancer metabolism will...
Article
Full-text available
Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially...
Article
Full-text available
The ectonucleoside triphosphate diphosphohydrolase (CD39)/5' ectonuclotidase (CD73)-dependent purinergic pathway emerges as promising cancer target. Yet, except for own previous work revealing a pathogenic role of CD73 and adenosine in radiation-induced lung fibrosis, the role of purinergic signaling for radiotherapy outcome remained elusive. Here...
Article
Full-text available
Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons a...
Article
Full-text available
Proton beam therapy is increasingly applied for the treatment of human cancer, as it promises to reduce normal tissue damage. However, little is known about the relationship between linear energy transfer (LET), the type of DNA damage, and cellular repair mechanisms, particularly for cells irradiated with protons. We irradiated cultured cells deliv...
Article
Full-text available
The survival kinase protein kinase B (Akt) participates in the regulation of essential subcellular processes, e.g., proliferation, growth, survival, and apoptosis, and has a documented role in promoting resistance against genotoxic stress including radiotherapy, presumably by influencing the DNA damage response and DNA double-strand break (DSB) rep...
Poster
The quantitative analysis of cells and foci plays a key role in various cell biological methods. In the field of radiation biology and molecular radiation oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction is detected by the analysis of protein clusters or phosphorylated proteins recruited...
Article
Full-text available
Genetic alterations driving aberrant activation of the survival kinase Protein Kinase B(Akt) are observed with high frequency during malignant transformation and cancer progression. Oncogenic gene mutations coding for the upstream regulators or Akt, e.g., growth factor receptors, RAS and phosphatidylinositol-3-kinase (PI3K), or for one of the three...
Article
Full-text available
The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated prot...
Article
Full-text available
The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq anal...
Data
Expression level of ORs in HCT116 cells. (A) Bar chart showing ranking of OR expression in HCT116 cells. (B) Read coverage of OR51B4 detected in HCT116 and visualized by the Integrative Genomic Viewer. (C) Average RNA-Seq transcriptome data for OR51B2, OR51B4 and OR51B5 from 5 different data sets. (TIF)
Data
Reverse transcriptase PCR (RT-PCR). The mixture contained 10 ?l of GoTaq qPCR Master mix, 50 pmol Primers (fwd+rev) and cDNA (equivalent of 50 ng of total RNA). The PCR reaction contained the following steps: 3 min at 95?C followed by 40 cycles of 1 min at 59?C (OR51B4) or 60?C (PLC, TBP) and 1 min at 72?C and was performed in the Mastercycler? ep...
Data
Expression of signaling pathway components in HCT116 cells validated by RNA-Seq and RT-PCR. ADCY3: adenylyl cyclase 3, GNAQ: G-protein ?q, GNAL: G-protein ?olf, GNAI1/3: G-protein ?i, CNGA1-4: CNG channel subunits (CNGA2, CNGA4, CNGA3, CNGA4, CNGB1 and CNGB3), OMP: olfactory marker protein, ANO2: calcium-activated chloride channel anoctamin 2, REEP...
Data
List of Henkel odorants in Henkel 100. Geranonitrile, acetophenone, eucalyptol, thymol, anethole, menthol, camphor, muscone, citronellol, sweet orange oil, p-cymene, eugenol, geraniol, hedione, helional, lyral, d-carvone,l-carvone, citral a, benzyl acetate, sassafras oil, 15-pentadecanolide, methyl salicylate, linalool, phenylethyl alcohol, hexyl c...
Data
Long-term application of Troenan (300 ?M) on HCT116 cells. HCT116 cells exposed to Troenan (300 ?M) for 20 minutes. ATP served as a control. (TIF)
Article
Full-text available
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While t...
Article
Full-text available
Transient receptor potential (TRP) channels contribute to the regulation of intracellular calcium, which can promote cancer hallmarks in cases of dysregulation of gene transcription and calcium-dependent pro-proliferative or anti-apoptotic mechanisms. Several studies have begun to elucidate the roles of TRPV1, TRPV6, TRPM8, and TRPC1 in cancer prog...
Conference Paper
Full-text available
The quantitative analysis of cells and foci plays an important role in various cell biology methods. In the fields of radiation biology and molecular radiation oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction is performed by the analysis of protein clusters or phosphorylated proteins rec...
Conference Paper
Full-text available
Research question: The survival kinase Akt1 is known to be aberrantly activated and to promote cell survival after genotoxic stress in various human tumors. Recent publications showed a decrease of DNA-dependent Protein Kinase (DNA-PK) dependent double strand break (DSB) repair after pharmacological inhibition of Akt. Accordingly, an interdependenc...
Conference Paper
Full-text available
Research question: The survival kinase Akt1 is known to be aberrantly activated and to promote cell survival after genotoxic stress in various human tumors. Recent publications showed a decrease of DNA-dependent Protein Kinase (DNA-PK) dependent double strand break (DSB) repair after pharmacological inhibition of Akt. Accordingly, an interdependenc...

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Projects

Projects (3)
Project
Free and user-friendly foci counting! https://focinator.com/
Project
Role of the PI3K/Akt pathway in the cellular radiation response
Project
The survival kinase AKT is aberrantly activated in various human tumors. Although recent investigations showed that inhibition of AKT decreases DNA-PKcs dependent DNA double strand break (DSB) repair (non-homologous end joining, NHEJ), the mechanisms how AKT affects DNA repair are still unclear. We used a genetic approach to study the role of AKT in the repair of radiation-induced DNA damage.