I have been fortunate enough to conduct research at the University of Texas Institute of Geophysics in high school, and while I enjoyed my work there I knew I wanted to work in a wet lab. Using CURF’s Research Directory I was able to find the Poncz Lab out of the Division of Hematology at CHOP. Our lab as a whole seeks to understand the mechanisms that govern hematopoiesis and megakaryopoiesis. In my current project with Dr. Brian Estevez, I am attempting to understand the processes that are dysregulated in Familial Platelet Disorder with predisposition to Acute Myelogenous Leukemia (FPD/AML), an autosomal dominant disorder caused by a mutation to the RUNX1 transcription factor, while attempting to further characterize the patient phenotype in patient-derived iPS cell culture. Penn is a truly unique place that is the focal point of research and intellectual discourse in all fields. We are truly fortunate to have a multitude of opportunities and resources at our disposal. The only problem is determining which path of research is right for you and using Penn’s resources to get started on that path. That’s what CURF and I am here to help you do. Please feel free to contact me if you are interested in research, especially in the biomedical field!
- University Scholars C’21
- Research Assistant, Poncz Lab, Division of Hematology, Children’s Hospital of Philadelphia
- Woodrow Wilson Undergraduate Research Fellowship at Johns Hopkins University (turned down)
- Research Assistant, University of Texas Institute for Geophysics
- Research Assistant, Diabetes Research Center, Children’s Hospital of Philadelphia
2018 UScholars Progress Report
Update on research project:
Familial Platelet Disorder with predisposition to Acute Myeloblastic Leukemia, or FPD/AML, is an autosomal dominant disorder characterized by thrombocytopenia, platelet dysfunction, and a lifelong risk of developing cancer. As a result of the first two defects, patients tend to be predisposed to bleeding and experience more bleeding than patients without the disorder. However, this bleeding tends to be more severe than is to be expected based on the degree of thrombocytopenia. The three defects described above are the result of mutations in the RUNX1 gene, which encodes a transcription factor of the same name. RUNX1 acts at many stages in megakaryocyte development, initiating definitive hematopoiesis and promoting megakaryopoiesis. FPD/AML manifests in-vitro as a megakaryocyte production defect, with the megakaryocyte-platelet axis unaffected in murine models. Our investigation of FPD/AML aims to discover pharmaceutical compounds that correct RUNX1 expression and/or activity, thereby correcting the platelet and hematopoietic progenitor cell defect and to identify points of dysregulation in associated cytokine pathways.
Previous work done in house has shown that the administration of RepSox, a TGFβR1 inhibitor, improves megakaryocyte yields in patient derived induced-pluripotent stem cells, suggesting the involvement of the TGFβ family of cytokines in FPD/AML. The TGFβ family constitutes a multifunctional set of cytokines that regulate a massive array of cellular processes during development and beyond. With respect to hematopoiesis, TGFβ plays an important role in regulating hematopoietic stem cell (HSC) behavior, particularly quiescence and self-renewal. Several molecular mechanisms have been proposed to account for TGFβ-mediated growth inhibition, including alteration in receptor expression and upregulation of cyclin-dependent kinase inhibitors such as p21 and p27. Preliminary data has shown p21 levels to be upregulated four to five times in patient-derived cells relative to isogenic controls. My current work focuses on better understanding the role of cell cycle modulators, namely p21, in FPD/AML.