Author Interviews, Duke, Leukemia, Nature / 12.12.2025
Duke and Duke-NUS Scientists Identify Metabolic Vulnerability in AML Using New Computational Approach
MedicalResearch.com Interview with:
[caption id="attachment_71759" align="alignleft" width="200"]
Dr. Matthew Hirschey[/caption]
Matthew Hirschey Ph.D.
Associate Professor of Medicine
Associate Professor of Cell Biology
Associate Professor in Pharmacology and Cancer Biology
Member of the Duke Cancer Institute
Member of Sarah W. Stedman Nutrition and Metabolism Center
Hirschey Lab in the Duke Molecular Physiology Institute,
Duke University
MedicalResearch.com: What is the background for this study? Would you briefly describe AML and why new therapeutic approaches are needed?
Response: Acute myeloid leukemia (AML) is an aggressive blood cancer that begins in the bone marrow and progresses rapidly. While recent advances, particularly the BCL-2 inhibitor venetoclax combined with other agents, have improved outcomes for some patients, many still relapse or don't respond to treatment. The five-year survival rate remains below 30% overall, highlighting an urgent need for new therapeutic strategies.
We know that cancer cells rewire their metabolism to fuel rapid growth, and the mitochondria (the cell's powerhouses) play a central role. However, understanding exactly how different metabolic pathways connect and depend on each other has been challenging. We wanted to develop better tools to map these connections and identify new vulnerabilities we could potentially target.
Dr. Matthew Hirschey[/caption]
Matthew Hirschey Ph.D.
Associate Professor of Medicine
Associate Professor of Cell Biology
Associate Professor in Pharmacology and Cancer Biology
Member of the Duke Cancer Institute
Member of Sarah W. Stedman Nutrition and Metabolism Center
Hirschey Lab in the Duke Molecular Physiology Institute,
Duke University
MedicalResearch.com: What is the background for this study? Would you briefly describe AML and why new therapeutic approaches are needed?
Response: Acute myeloid leukemia (AML) is an aggressive blood cancer that begins in the bone marrow and progresses rapidly. While recent advances, particularly the BCL-2 inhibitor venetoclax combined with other agents, have improved outcomes for some patients, many still relapse or don't respond to treatment. The five-year survival rate remains below 30% overall, highlighting an urgent need for new therapeutic strategies.
We know that cancer cells rewire their metabolism to fuel rapid growth, and the mitochondria (the cell's powerhouses) play a central role. However, understanding exactly how different metabolic pathways connect and depend on each other has been challenging. We wanted to develop better tools to map these connections and identify new vulnerabilities we could potentially target.
Dr. Moyland[/caption]
Cynthia Moylan, MD
Associate Professor of Medicine,
Division of Gastroenterology
Duke University Health System
MedicalResearch.com: What is the background for this study?
Response: Metabolic dysfunction can lead to several health problems including metabolic dysfunction associated steatotic liver disease (MASLD), is driven by different factors, including: a person’s behavioral or lifestyle factors, environmental factors, and genetics. Limited research exists regarding genetic , epigenetic, or other factors that might impact development of metabolic dysfunction and MASLD. Our group has previously shown that alterations in DNA methylation (a type of epigenetic change), identifiable both in liver tissue and in blood, associate with MASLD and its progression to more severe liver disease. Whether DNA methylation that impacts imprinted gene expression also associates with metabolic dysfunction and MASLD risk remains largely unknown.
In this project, we explored imprinted genes: imprinting is a normal process that regulates genes by silencing one parental copy (either the maternal or the paternal) so that only one copy is expressed. Imprinting is an important biological process for development and has a disproportionate impact on disease - in fact, imprinted genes are hypothesized to affect 1-6% of the human genome. We sought to explore how altered DNA methylation of imprint control regions (ICRs) that help ‘control’ these imprinted genes might impact development of metabolic dysfunction in children (and hence potentially even in adults).

