# The role of the histone chaperone Chaf1b in sustaining the Hoxa9-driven AML differentiation block > **NIH NIH K22** · UNIVERSITY OF PENNSYLVANIA · 2020 · $190,620 ## Abstract Project Summary/Abstract I received my undergraduate degree from Cornell University, my PhD in molecular biology from Princeton University, and am currently a postdoctoral researcher and Special Fellow of the Leukemia and Lymphoma Society at Harvard Medical School and Boston Children's Hospital. After studying the molecular basis of breast cancer metastasis in graduate school, I transitioned to the field of epigenetics in the laboratory of Yang Shi for my postdoc. I have received extensive experimental and scholarly training in my postdoc. I learned the rigors of basic chromatin biochemistry in my first postdoctoral project, and recently published a co-first author paper based on this work. This study was featured as the cover article in the journal Cell and reported the identification of a novel metazoan epigenetic DNA modification, N6-methyladenine (6mA). My scholarly training has involved extensive scientific writing and has enabled me to write three successful postdoc fellowship applications (from the NIH, ACS, and LLS), two successful grants for Dr. Shi based on my work (from the Samuel Waxman Cancer Research Foundation and the Harvard Epigenetics Initiative), and one recently published review paper as a co-author in the journal Nature Reviews Molecular Biology. My current postdoctoral research merges my background in cancer biology with my recent training in chromatin biochemistry and focuses on the epigenetic basis of the differentiation block that characterizes acute myeloid leukemia (AML). AML is the most lethal hematological malignancy and is the cause of more than 10,000 annual US death. AML is typically treated by chemotherapy, though patients often relapse and have limited therapeutic options. The promyelocytic subtype of AML can be cured by “differentiation therapy” – induction of differentiation and inhibition of proliferation with retinoic acid – but this approach has been ineffective in other AML subtypes. Recent work has suggested that this block to non-APL AML differentiation is epigenetic in nature. Stable – yet reversible – chromatin alterations are thought to disable myeloid differentiation gene expression programs in these cells. I have recently established a robust genetic screening approach to uncover epigenetic regulators of non-APL AML differentiation programs. These screens have identified the Chaf1b subunit of the Caf-1 histone remodeling complex as a critical regulator of the Hoxa9- driven AML differentiation block. The overall goal of the work proposed in this application is to determine the molecular, chromatin-based mechanisms by which Chaf1b functions to regulate AML cell differentiation. The goal of my first Aim in this proposal is to use biochemical approaches to identify the proteins and long non- coding RNAs (lncRNAs) that associate with Chaf1b and the greater Caf-1 complex in AML cells. I will then focus on determining which of these interacting proteins and RNAs are most critical in recruiting Chaf1b to its... ## Key facts - **NIH application ID:** 9999460 - **Project number:** 5K22CA214849-03 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** Mario Andres Blanco - **Activity code:** K22 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $190,620 - **Award type:** 5 - **Project period:** 2018-09-01 → 2022-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9999460 ## Citation > US National Institutes of Health, RePORTER application 9999460, The role of the histone chaperone Chaf1b in sustaining the Hoxa9-driven AML differentiation block (5K22CA214849-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999460. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*