Publications

Publications

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Publications by Dr. Thomas Klonisch

In his translational Oncology research projects, Dr. Thomas Klonisch mainly focuses on mechanistic studies to better understand therapeutic resistance in tumors, with a particular emphasis on Brain Tumors. His published work includes receptor signaling events affecting cell radio-/chemo-resistance and cell plasticity (EMT, stemness), drug nanocarriers, ER stress and unfolded protein response (UPR), cell death mechanisms (apoptosis, autophagy), and the effect of novel therapeutics on cancer (stem) cells and innate immune cells in the tumor micro-environment.

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Publications by Dr. Sabine Hombach-Klonisch

The cancer research program of Dr. Hombach-Klonisch focuses on the cellular mechanisms that drive late stage cancer progression and therapeutic resistance in glioblastoma and in brain metastatic breast cancer. Her interest is to identify molecular mechanisms and cellular signaling events that promote cancer cell survival under cellular stress, including DNA stress and endoplasmic reticulum stress, which can be targeted to improve treatment success.  She investigates the influence of brain resident cells of the perivascular niche, such as pericytes and brain endothelial cells, on these cancer cell stress responses.  

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FEATURED PAPER ABSTRACTS

A1: HMGA2 is a new interaction partner of PARP1

KEY FINDINGS

  • HMGA2 increases the resistance to PARP1 inhibitor Olaparib
  • HMGA2 interacts with PARP1 and reduces PARP1 trapping at DNA damaged sites
  • HMGA2 enhances PARP1 activity and supportive mitochondrial and metabolic changes

A2: C1Q-Tumor Necrosis Factor related Peptide 8 (CTRP8) is a new ligand of the relaxin receptor RXFP1

KEY FINDINGS

  • CTRP8 is a novel RXFP1 agonist expressed in human glioblastoma (GBM) cell lines and patient GBM cells
  • CTRP8 promotes PI3K and PKCδ/τ signaling and enhanced Cathepsin-B secretion
  • CTRP8 peptides enhance the motility and matrix invasiveness of patient GBM cells

A3: CTRP8 promotes STAT3 mediated resistance to Temozolomide in GBM cells

KEY FINDINGS

  • CTRP8-RXFP1 interaction activates the STAT3 pathway
  • CTRP8 reduces Temozolomide (TMZ) induced DNA damage by increasing the expression and activity of N-methylpurine DNA glycosylase (MPG)
  • CTRP8 promotes resistance to apoptosis under TMZ treatment

A4: Mechanisms of therapeutic resistance in cancer (stem) cells with emphasis on thyroid cancer cells.

REVIEW

This review highlights mechanisms of therapy resistance in heterogeneous solid tumors that are linked to epithelial-mesenchymal transition, DNA repair capabilities, autophagy and endoplasmic reticulum stress.

A5: Role of cell death mechanisms and unfolded protein response in glioblastoma (GBM) chemoresistance

REVIEW

In this review, we summarize the impact of DNA alkylating drugs, like the GBM standard treatment drug Temozolomide, on resistance mechanisms initiated by GBM, with a particular emphasis on cell death mechanisms, endoplasmic reticulum stress and unfolded protein responses.

A6: Modulation of Wnt/β-catenin signaling promotes blood-brain barrier phenotype in cultured brain endothelial cells

KEY FINDINGS

This work was done in collaboration with Dr. Don Miller, Dept. of Pharmacology, University of Manitoba.

  • TGF inhibitor-mediated blocking of intrinsic Wnt/β-catenin signaling in hCMEC/D3 human brain endothelial cells diminished electrical impedance and caused a reduction in the expression of selected junctional and transporter proteins.
  • Exogenous activation of Wnt signaling improved barrier function. This was associated with the reduction of the plasmalemma vesicle-associated protein PLVAP

A7: A novel microfluidics device to monitor and quantify chemotaxis of tumor cells

KEY FINDINGS

This work is done with our collaborator Dr. Francis Lin, Professor, Dept. of Physics and Astronomy, University of Manitoba. The new radial microfluidics device can run eight chemotaxis experiments simultaneously with monitoring and quantification at the single cell level.

A8: Unlocking bone for proteomic analysis

KEY FINDINGS

This work was done in collaboration with Dr. Claudius Mueller and Dr. Virginia Espina, George Mason University, Fairfax, Virginia, USA.

  • A new fixative (theralin) was developed that is superior to formalin for the fixation of bone tissue. It simultaneously fixes and decalcifies bone tissues.
  • Theralin is superior to formalin in preserving histological structure, protein and DNA for histomorphological studies in specimens of osteosarcoma and bone metastatic tissues.