Begriffe, Krankheiten, Einrichtungen u.v.m., verknüpft mit dem zuständigen Bereich.
Im Menüpunkt "Übersicht" sind Einrichtungen unter verschiedenen Gesichtspunkten gruppiert: Kliniken, Abteilungen, Institute, Zentrale Einrichtungen und ähnliches.
Research
Nonrandom Selection of a Cooperative Genetic Landscape During Glioma Evolution
Research at large has mainly focused on target genes within individual chromosomal aberrations. However, these aberrations do not exist in isolation; rather there may be mechanistic links to genes at other, coincident aberrations.
By linking network modeling of high-dimensional DNA and RNA data to the known functional interactions of genes, we have described a nonrandom genetic landscape that, through its facilitation of altered gene interactions, promotes gliomagenesis.
Our main goal is to further characterize this landscape topologically and dynamically as well as individual gene relationships as a means to identify new leads for targeted therapies for high-grade gliomas.
Molecular targeting of networking landscape genes may offer targets for more effective treatments. One such relationship includes the EGFR oncogene on chromosome 7p11.2 and a tyrosine phosphorylation target of EGFR on chromosome 10q, ANXA7. ANXA7 is a novel tumor suppressor which attenuates EGFR signaling.
We have shown ANXA7 to be significantly affected in its expression (and potentially its posttranscriptional regulation) by the frequent mono-allelic loss of 10q in glioblastomas. We are currently exploring the mechanism of dergulation of this ANXA7 and its isoforms in glioblastomas, its mechanism of interaction with EGFR, and the potential value of combined targeting of both genes in these tumors as a new therapeutic avenue.
Dysregulation of Nuclear Factor-κB in High-Grade Gliomas
Nuclear factor-κB (NF-κB) is a eukaryotic transcription factor on the crossroad of a cell’s decision to live or die. NF-kB is excessively activated under several pathological cell conditions, allowing cells to escape programmed cell death. Escape from apoptosis is a common pro-survival mechanism induced by genotoxic stress that could affect all major therapeutic regimens considered standard of care in high-grade gliomas, including chemotherapy with O6-alkylating agents and radiation therapy.
Although various routes can lead to NF-kB activation, evidence suggests that the so-called canonical pathway is predominantly involved in high-grade gliomas. Canonical NF-κB activation involves divergent signaling cascades that ultimately converge to activate the inhibitor of kB kinase (IKK) signalosome. While the mechanisms of NF-κB activation have been well studied, the mechanisms by which NF-κB is regulated are less well understood. We have identified several networking endogenous modulators of NF-κB activation that affect cell resistance and patient outcomes in high-grade gliomas.
We have confirmed the power of those modulators to predict the outcome of high-grade glioma patients in several independent validation cohorts from different academic institutions. Our research focus is on the regulation of these modulators and the role the dysregulation of the modulators may have in tumorigenesis.
