Control of the MYC super-enhancer complex in FLT3-ITD acute myeloid leukemia
Ended Project Grant Awarded Last action
- Award ID
- F30CA278500
- Recipient
-
Oregon Health & Science University UEI NPSNT86JKN51
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $160,762
Award facts
- Assistance listing
- 93.398 Cancer Research Manpower
- Completion date
- Place of performance
- Oregon, USA
Award details come from USAspending.gov.
Description
- Abstract
- Acute myeloid leukemia (AML) is an aggressive blood cancer with a 5-year expected survival rate of less than 30%. Internal tandem duplications (ITD) of FMS-like tyrosine kinase 3 (FLT3) is a common mutation in AML and is a molecular driver of immature blood cell proliferation. Despite advances in the development of FLT3 kinase inhibitors, remissions are short-lived. I have previously shown that inhibition of the epigenetic regulator lysine-specific demethylase 1 (LSD1) enhances the efficacy of FLT3 inhibitors in FLT3-ITD AML. The drug combination induces leukemic cell death by disrupting regulatory binding at the MYC blood-specific super- enhancer complex (benc), resulting in a loss of activity and expression of the MYC proto-oncoprotein. In aim 1, i will use single cell chromatin accessibility sequencing and high-resolution epigenetic profiling of primary AML samples to define the transcription factor regulators of the MYC benc in FLT3-ITD AML. In aim 2, i will use activating crispr technology and drug sensitivity assays to identify the individual MYC benc enhancer modules that are critical for the activity of combined FLT3 and LSD1 inhibition. Successful completion of these studies will determine the molecular control of the MYC benc in FLT3-ITD AML, nominating novel targets and enabling personalization of dual FLT3 and LSD1 inhibition for patients with FLT3-ITD AML. My goal is to manage an independent systems biology research group that investigates molecular leukemia biology and targeted leukemia therapies while simultaneously practicing as a hematologist oncologist at an academic research institute. This application proposes a comprehensive and interdisciplinary training plan within a prominent academic medical and research institution that seamlessly integrates with the research proposal and provides essential training in computational and molecular cancer biology. I will receive guidance in drug sensitivity and functional genetic techniques as well as access to one of the largest AML patient biorepositories in the world from my sponsor, DR. Brian druker, a pioneer in the field of targeted leukemia therapy and director of the knight cancer institute. I will be supported in analysis of single cell sequencing data from my CO-sponsor, DR. Emek demir, the section head of computational biology at the knight cancer institute. I will learn to apply high-resolution epigenetic profiling techniques to investigate epigenetic regulatory mechanisms in leukemia from my CO-sponsor, DR. Theodore braun, a physician-scientist and assistant professor of hematology & medical oncology. I will be trained in the use of single cell chromatin accessibility sequencing from a leader in single cell sequencing technologies, DR. Andrew adey. I will learn to use integrative systems biology techniques to study targeted leukemia therapies from my thesis advisory committee member, DR. Laura heiser. I will learn to design and test my hypotheses in the context of therapeutic responses in cancer from my thesis advisory member, DR. Naoki oshimori.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$9,122 | |
| Amendment | -$20,446 | |
| Amendment | -$20,446 | |
| Amendment | $52,694 | |
| Amendment | $52,694 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $52,694 | |
| Amendment | $0 | |
| Original award | $52,694 |
Quick answers
Who received award F30CA278500?
F30CA278500 was awarded to Oregon Health & Science University by National Cancer Institute (National Institutes of Health) on June 1, 2024.
How much is award F30CA278500 worth?
$160,762 has been obligated on F30CA278500.
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