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:
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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.
Ben Petrazzini[/caption]
Ben Omega Petrazzini, B.Sc.
Associate Bioinformatician
Dr. Callaghan[/caption]
Bridget Callaghan Ph.D.
Assistant Professor of Psychology
UCLA
Dr. Callahan studies interactions between mental and physical health across development.
MedicalResearch.com: What is the background for this study?
Response: A growing body of evidence links the gut microbiome to brain and immune functioning, and changes to that community of microorganisms is likely among the ways that hardship affects children’s socioemotional development.
Limited evidence in humans has demonstrated the adversities experienced prenatally and during early life influence the composition of the gut microbiome, but no studies had examined whether stress experienced in a mother's own childhood could influence the microbiome of the next generation of children.
Dr. Tsirigos[/caption]
Aristotelis Tsirigos, Ph.D.
Professor of Medicine and Pathology
Co-director, Precision Medicine
Director, Applied Bioinformatics Laboratories
Dr. den Hoed[/caption]
Marcel den Hoed, PhD
Researcher,Department of Immunology, Genetics and Pathology
Uppsala University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In this paper we performed a multi-ancestry meta-analysis of 51 genome-wide association studies, in data from over 700,000 individuals. This yielded 11 DNA regions that are robustly associated with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), and 88 DNA regions for self-reported leisure screen time (LST).
Around half of the identified DNA regions are also associated with objectively assessed physical activity traits in data from the UK Biobank. Causal inference using a Mendelian randomization approach subsequently showed bidirectional causal effects between LST and body mass index (BMI), with the effect of LST on BMI being 2-3-fold larger than vice versa. Less LST and more MVPA protect from diabetes, attention deficit hyperactivity disorder, depression, and earlier age at death, with all causal effects of MVPA and leisure screen time being mediated or confounded by BMI. Further analyses showed that DNA regions associated with LST are more often located close to genes whose expression in skeletal muscle is altered by strength training than expected by chance, suggesting that these genes may influence the likelihood of adopting an active lifestyle by influencing the response to training.
Dr. Giebultowicz[/caption]
Dr. Jaga Giebultowicz
Professor Emeritus,
Department of Integrative Biology
Oregon State University
Corvallis, OR 97331
MedicalResearch.com: What is the background for this study? Where is blue light commonly found?
Response: Our study in short-lived model organism Drosophila revealed that cumulative, long-term exposure to blue light impacts brain function, accelerates the aging process and significantly shortens lifespan compared to flies maintained in constant darkness or in white light with blue wavelengths blocked.
Blue light is predominantly produced by the light-emitting diodes (LEDs); it appears white due to the addition of yellow fluorescent powder which is activated by blue light. LEDs has become a main source of display screens (phones, laptops, desktops, TV), and ambient lights. Indeed, humans have become awash in LEDs for most of their waking hours.
Dr. Piantino[/caption]
Juan Piantino, M.D., MCR
Assistant Professor of Pediatrics
Division of Neurology, School of Medicine
Director, Inpatient Child Neurology
Oregon Health Sciences University
MedicalResearch.com: What is the background for this study?
Response: Astronauts are exposed to several stressors during spaceflight, including radiation, lack of gravity, and sleep deprivation. The effects of those stressors on the brain remain unknown. Is it safe to travel to space? For how long can humans survive in space? What are the effects of spending months under zero gravity? With more extended missions, and an increased number of civilians traveling to space, there is increased interest in understanding what happens to our brains when we leave earth.
Dr. Anderson[/caption]
Dr. Weston B Anderson PhD
Postdoctoral Reasearch Scientist
International Research Institute for Climate and Society
The Earth Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We find that while drought continues to be a consistent trigger of food crises in Sub-Saharan Africa, protracted conflict has become relatively more important over the last decade.
We furthermore find that pastoral livelihoods have taken longer to return to food secure conditions following droughts as compared to agricultural livelihoods.
Prof. Monsonego Ornan[/caption]
Efrat Monsonego Ornan, Ph.D
Head of School of Nutritional Sciences
Institute of Biochemistry and Nutrition
The Robert H. Smith Faculty of Agriculture,
Food and Environment
The Hebrew University of Jerusalem
MedicalResearch.com: What is the background for this study?
Response: Food supplies in recent decades have been dominated by heavily processed, ready-to-eat products. Essentially, 75% of all world food sales are of processed foods. Over the past 30 years, children’s ultra-processed food intake has increased markedly, with 50% of the children in the US consuming these foods. Only in the US does UPF comprise 58% of energy intake, of which 90% is derived from added sugars. This reflects children’s excessive consumption of food and drink that are high in fat and refined sugars but do not provide appropriate levels of the proteins, vitamins and minerals required for growth.
The negative health outcomes of excessive consumption of Ultra-processed food are well known, include obesity, metabolic syndrome and diabetes, and considered as the current world epidemic; the fact that children, during their postnatal development period (birth to adolescent), are the target of the Ultra-processed food industry is very disturbing in terms of public health. Bone development and growth are the characteristic phenomena of the childhood period. Yet, in spite of the huge importance of nutrition to bone development, the impact of Ultra-processed food consumption on skeleton development during childhood has never been studied directly, and this was the purpose of our study.
To this end, we used young rats which are an excellent pre-clinical model for growth and fed them with either the recommended diet for their age or a diet comprised of a typical Ultra-processed meal (a roll, hamburger, tomatoes, lettuce, ketchup and French fries) and a caloric soft drink. 
