 Hello, my name is Mariana Parabichka and I am a research associate at the Galat Laboratory, which is located at the Simpson Quarry Biomedical Research Center and affiliated with Anne and Robert H. Lurie Children's Hospital and Northwestern University-Findberg School of Medicine. On behalf of all the authors, I would like to say thank you for the opportunity to present this research. Hello, my name is Ekaterina Galat. I am also a research associate in the Galat Laboratory. Together with Mariana, we are the lead co-authors on our paper titled Down Syndrome-induced pluripotence stem cell model in the thylial insights into tumor development. My name is Vasily Galat and I am head of the lab. My lab has a long-standing interest in disease modeling. In fact, we are the first to establish embryonic stem cells from human embryos with genetic disease. These days, we are using reprogramming technology to develop patient-specific induced pluripotence stem cells or IEPCs. These stem cells can be differentiated into different type of cells and used for research and testing. This concept is known as a disease in the dish. The Galat Laboratory has several ongoing projects involving hematopoietic differentiation. For instance, we study natural killer cells produced from IEPCs for immune therapy applications. In this particular paper, we are presenting our investigation of IEPCs derived in the thylial cells. When the thylial cells play a pivotal role in blood formation and we shoot them to study trisomy, chromosome 21 implication on leukemia development in down syndrome patients. And the thylial cells are not easily attainable from patients. This is why our endothelial IPAC model proves to be so useful. While deriving endothelial cells from down syndrome patients, we noticed that down syndrome proliferative response to vascular endothelial growth factor differed from control IPACs. This finding coupled with clinical data showing that down syndrome patients have high incidence of leukemia and decreased solid tumor prevalence motivated us to further analyze this down syndrome endothelial progenitors. For this study, we performed endothelial derivation, bioinformatic analysis and functional assays. Regarding the bioinformatic component, we utilized various cancer databases and carried out extensive pathway analysis. The functional assays targeted proliferation, migration and inflammatory response, which are processes that tumors employ to create a favorable niche for growth in order to transition into a more invasive phenotype. Our analyses revealed several notable aspects. For example, we observed an increased expression in leukemia-associated oncogenes. So for example, gata 2 and notch 1, and decreased expression of genes involved in regulating inflammation, such as IL-6, IL-8, CCl2. And we believe that this genetic profile is contributing toward a leukemia- conducive microenvironment. And importantly, most of our identified endothelial genes have not been previously highlighted in down syndrome research, which is predominantly centered around genes expressed on chromosome 21. I would say that one of the most challenging aspects about this study was the optimization of endothelial derivation to ensure that our endothelial progenitors demonstrate the appropriate molecular and phenotypic characteristics. At the time when this study was initiated, an efficient endothelial derivation method was not available. As a result, we dedicated a significant amount of our time to establishing a robust endothelial differentiation protocol. A surprising aspect of this study was that the upregulated leukemia-associated oncogenes and the differentially expressed genes linked to proliferation, migration, and inflammatory response were actually not located on chromosome 21. And this significant finding emphasizes how trisomy 21 is capable of leading genome-wide alterations that result in down syndrome endothelial dysfunction and increased leukemic susceptibility. And we actually observed similar genome-wide dysregulation in a recently published parallel study that incorporates mesodermal cells. This work shows that processes underlying connective tissue impairment in down syndrome patients also potentially hinder solid tumor progression. So overall, down syndrome provides a unique, nontraditional lens to study tumor development. We defined a list of candidate gene of interest. The next step of our investigation would be to perform in vivo verification of these genes. If our results are confirmed, we might have new gene targets for leukemia treatment, which is very exciting. Thank you for your attention. Please read our paper and contact us with any questions you may have. Thank you again.