The objective of this funding program is to promote both basic and translational biomedical research, by bringing together scientists and physicians. The expectation is that this program will facilitate the incorporation of novel approaches from the bench to clinical applications.
Tumor microbiome and Glioblastoma: Characterization, effects and translational opportunities
Identifying microbial determinants of response and resistance to targeted therapy in melanoma
Mutations in the BRAF gene occur in over half of melanoma tumors and result in constitutive signaling of the mitogen activated protein kinase (MAPK) pathway leading to enhanced cellular proliferation and survival. Treatment with MAPK pathway inhibitors targeting this genetic abnormality is associated with clinical benefit in the majority of patients with BRAF-mutant melanoma. However, relapse is almost universal.
Targeting mutant p53 in glioblastoma by an exosome-based therapy
The tumor suppressor p53 is commonly mutated in glioblastoma, conferring it with aggressive oncogenic features. Consequently, we aimed to develop a new therapy approach for glioblastoma in which anti- mutant p53 drugs will be packaged into exosomes which then be delivered to patients for treatment. Previously, we were able to show that gliomas readily take up MSCs-derived exosomes and by that we were able to specifically change the gene expression and influence the biological behavior of glioma cells.
EPCR and TM Guide Hematopoetic Stem Cell Homing to the Bone Marrow without Niche Clearance
Bone marrow (BM) recognition, homing and lodgment of long term repopulating hematopoietic stem cells (LT HSCs) are essential first steps for durable blood cell production during embryonic development and in clinical stem cell transplantation. Rare, BM retained LT HSCs endowed with the highest repopulation potential highly express EPCR (endothelial protein c receptor) and PAR1, which control LT HSC retention and chemotherapy resistance by limiting nitric oxide levels. We found that transplanted EPCR+ LT HSCs preferentially home to the BM, in contrast to immature progenitors.
Omental fat-mediated chemoresistance to gastric cancer originating metastases
Omental spread is common in gastric adenocarcinoma, representing an advanced stage that harbors poor prognosis mostly due to resistance to systemic therapy. We have shown previously that factors secreted by fresh human omental-fat specimens induce chemoresistance of gastric cancer cells. In this project, we will further characterize the effects that omental-fat secreted factors have on the chemoresistance of gastric cancer. In vitro co-culture system will be used to systematically assay the effect of the different omental-fat secreted factors on chemoresistance.
