Summary We seek to decipher the contribution of RUNX1 to the phenotypes seen in individuals with Down syndrome. RUNX1 is a chromosome 21 encoded transcription factor involved in blood differentiation, a process known to be altered in individuals with Down syndrome. Since transcription factors bind to DNA and alter RNA polymerase activity we will determine if those two functions of RUNX1 are altered in individuals with Down syndrome. We will also determine if drugs that increase or inhibit RUNX1 function behave differently in cells with an extra copy of chromosome 21. Finally, we will determine how much of the altered blood differentiation seen in Down syndrome is caused by RUNX1 by dosage normalizing RUNX1 in a trisomy background (e.g.two copies in a trisomy cell line). We will then differentiation of iPSCs into embryoid bodies and blood cells. Collectively this work will shed insights into the functions of RUNX1 and how it is altered in Trisomy 21.