Grace Ozog
Pronouns: she/her
Research Mentor(s): Andrew Muntean
Co-Presenter:
Research Mentor School/College/Department: Pathology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 5 – 3:40pm – 4:30 pm
Room: League Ballroom
Authors: Grace Ozog, David Hu, Nirmalya Saha, Lauren Lachowski, Andrew Muntean
Presenter: 5
Abstract
MLL-rearranged (MLL-r) leukemia is a subgroup (~10%) of acute myeloid leukemia characterized with intermediate to poor prognosis. In MLL-r leukemias, the MLL gene (on chromosome 11) is fused to another fusion partner and creates the pathogenic MLL-r fusion protein. Over 100 different fusion partners have been identified, with the most common fusion partners (ENL, AF9, AF4, AF10, and ELL) accounting for over 80% of MLL-r cases. It has been demonstrated that these common fusion partners are part of the super elongation complex (SEC), which is misdirected to and dysregulates the expression of pro-leukemic targets (such as Hoxa9 and Meis1) in MLL-r leukemia. In my project, I specifically focus on the fusion partner ENL. ENL is a YEATS epigenetic reader domain containing protein that recognizes the histone H3K9, K18, and K27 acetyl marks. Previously, the Muntean lab has demonstrated the inclusion and importance of the YEATS domain in MLL-ENL fusion proteins in MLL-ENL leukemogenesis. In addition to the YEATS domain, the ENL protein also has the Anc1-homology domain (AHD) and the intrinsically disordered regions (IDR). The AHD interacts with SEC components and is necessary for MLL-ENL leukemogenesis. The IDR of wild type ENL has been shown to affect SEC functions through a process called liquid-liquid phase separation. However, the role of IDR and how it contributes to MLL-ENL leukemogenesis is unclear. To understand the contribution of ENL IDR in MLL-ENL leukemogenesis, I will generate MLL-ENL fusion constructs in the presence and absence of ENL IDR and ask how these constructs impact MLL-ENL cell proliferation and MLL-ENL leukemogenesis in vivo. I will also look at the expression of key proleukemic target genes such as Hoxa9 and Meis1. In summary, my project will help elucidate how important the ENL IDR is in MLL-ENL mediated leukemogenesis program.
Interdisciplinary, Natural/Life Sciences
