Cisplatin is one of the oldest and most widely used drugs for the treatment of cancer, but the use of the drug is limited both by severe dose-dependent side effects and by inherent or acquired resistance to treatment, which limits its efficacy. Although various derivatives of cisplatin have been synthesized and approved, they have not been able to effectively overcome the resistance to most cancers, so the need for a new molecule still exists.
In her research, Yaara will engage in a new derivative of cisplatin and its effects and mechanism of activity in various types of cancer cells. The derivative will be based on cisplatin, to which two inhibitors will be picked up for different cellular pathways, known to be over-activated in resistant cancer cells. The first path is a pathway that is responsible for gene expression of protective proteins and neutralizing toxins in cells, and the second path is responsible for DNA compression, and the combination of inhibitors with cisplatin in a single molecule has the potential for increased and more effective activity of cisplatin, Which will also provide a solution for cancer patients who are currently receiving treatment with severe side effects, and also for patients who are currently not treated with cisplatin.
Allergic inflammation (AI) is a reaction that occurs in diseases such as asthma, atopic dermatitis, and food allergy. In genetically predisposed (atopic) subjects, repeated allergen exposure can lead to chronic AI, which is still an important unmet clinical need. Therefore, it is most important to develop new therapeutical strategies against allergic inflammation, involving for example inhibitory receptors (IRs) and resolution pathways.
Part of my research focuses on the inhibitory receptor CD300a and its role in resolution of inflammation. The particularity of this receptor lies in its ability to bind lipids, especially phosphatidylserine expressed on the membrane of activated or apoptotic cells. The hypothesis is that modulation of this receptor, as expressed by the cardinal cells of allergy, mast cells and esoinophils, might positively influence the course of inflammation. This study involves the use of CD300a KO mice.
Secondly, I study the pro-resolutory lipid mediators Resolvin D1 and Lipoxin A4, their effect on and their production from mast cells and eosinophils and their co-culture. Preliminary results show that these molecules, once bound to their surface receptors, can decrease the inflammatory signals and production of pro-inflammatory mediators.
Ongoing projects are focusing on investigating whether mast cells might have a pro-resolutory role in AI in vitro and in vivo.
This research is conducted in collaboration with Bruce D. Levy's laboratory at the Brigham and Women's Hospital, Harvard Medical School, Boston.
Reproduction is a fundamental process that enables the survival of species. However, in humans this process is relatively ineffective, leaving 20-30% of couples temporarily, and 10% of couples permanently childless. Previous research that was done, shows that metabolic changes (i.e. changes in the concentration of small molecules) play central roles in embryo development and blastocyst implantation. However, only fragments of the metabolic network and the mechanisms regulating these processes are known to date.
In her work, Reut is studying the metabolism and metabolic interactions between different populations of pre-implantation embryonic cells and during the differentiation of these cell populations.
Reut found distinct metabolic changes that are important for the early differentiation of embryonic cells and is working on deciphering the complex metabolic pathways that cause these changes.
In future projects, Reut would like to explore the metabolic influence on differentiation of embryonic stem cells to fully differentiated cells and to explore the metabolic interactions between cell populations in the pre-implanted embryo. She hopes to suggest new mechanisms that will better explain processes during embryo development. Potentially she hopes to offer pharmaceutical-metabolic interventions that will elevate blastocyst implantation rates.