AACR-PCWG Across the Map: Researcher Spotlight
In this feature, Samrat Roy Choudhury, PhD, shares how his laboratory is working to turn the molecular biology of high-risk, fusion-driven pediatric AML into new therapeutic opportunities, from understanding unusual enhancer biology to identifying vulnerabilities that persist after treatment resistance emerges.
Beyond the science, he discusses how Little Rock helped shape his research path, what he wishes funders better understood about pediatric cancer, and why writing fiction has become an important creative outlet.
RESEARCH
What are you most excited about with respect to your research?
I am most excited by the possibility that epigenetic changes often treated as markers of disease can actively sustain oncogenic transcription and therapeutic resistance. In fusion-driven pediatric acute myeloid leukemia (AML), our work has uncovered an unusual pattern of DNA hypermethylation at cis-regulatory elements (CREs), particularly enhancers, where methylation coexists with transcriptionally permissive chromatin rather than simply marking gene repression. We are now asking how these altered regulatory elements engage target promoters through long-range chromatin interactions and whether disrupting these epigenetic dependencies can reveal new therapeutic vulnerabilities.
What emerging opportunities might your laboratory or research program explore next?
One emerging opportunity is to map and functionally interrogate the epigenomic architecture of CREs in high-risk AML, including their methylation, chromatin state, and long-range contacts. We are particularly interested in whether methylation at distal regulatory elements coordinates broader transcriptional programs and alters drug sensitivity or surface-antigen expression relevant to immunotherapy. In parallel, we are exploring previously unappreciated kinase dependencies that persist in therapy-resistant AML, with the goal of identifying vulnerabilities that remain actionable after resistance emerges.
What is one of your favorite scientific papers?
One paper I particularly value is Wilson et al., Leukemia (2022), “Focal disruption of DNA methylation dynamics at enhancers in IDH-mutant AML cells.” They identified focal hypermethylation preferentially at active enhancers, including regions with three-dimensional regulatory connectivity, without corresponding loss of H3K27ac or reduced expression of linked genes. This provides an intriguing counterpoint to our work in fusion-driven AML, where enhancer-associated methylation also coexists with transcriptionally permissive chromatin. Together, these observations underscore that enhancer methylation occurs in distinct regulatory contexts and that its functional consequences remain an important unresolved question in leukemia biology.
VISION
If you had unlimited resources, what is one clinical trial, experiment, or policy that you would enact today?
I would build on existing master-trial frameworks to establish a global adaptive precision-medicine platform specifically for rare, fusion-driven pediatric leukemias. Children would enter fusion-defined molecular cohorts and undergo rapid genomic and transcriptomic profiling integrated with functional drug-sensitivity and surface-antigen testing. Treatment could be reassessed as the disease evolves, while trial arms could open or close as evidence accumulates; an international structure would aggregate enough patients to study molecular subtypes that are otherwise too rare for conventional trials.
What is something unique about the way that you approach making an impact in pediatric cancer research?
For many high-risk, fusion-driven pediatric leukemias, direct pharmacologic inhibition of the fusion itself is not currently feasible. My approach is to identify the proteins and pathways required to establish and sustain the fusion-driven leukemic state, and then determine which of those dependencies are therapeutically tractable. This shifts the focus from a difficult-to-drug fusion protein to essential, therapeutically tractable dependencies of the fusion-driven leukemic state.
What would you want policymakers or funders to understand about the state of pediatric cancer research today?
Pediatric cancers cannot simply be approached as smaller versions of adult cancers. Many are biologically distinct, rare, and further divided into molecular subtypes with very small patient populations, making both research and clinical trial development unusually difficult. I would like to see a sustained, dedicated federal funding stream for childhood cancers, with particular support for rare and high-risk diseases that are unlikely to attract substantial commercial investment. Such funding is essential for the multi-institutional studies, shared resources, and collaborative trials needed to make meaningful progress.
What are the main challenges that remain to be addressed in your field, and how is your work helping to address them?
One of the biggest challenges in pediatric AML is that we can now define many high-risk leukemias at remarkable molecular resolution, but for too many children that information still does not change treatment. Fusion-defined subtypes are rare, often lack direct inhibitors, and treatment resistance remains a major problem. My laboratory is trying to close that gap by identifying what these leukemias depend on to grow and survive, and whether those dependencies can be converted into tractable therapeutic targets. Progress will also require broader access to patient samples, disease-relevant models, and multi-institutional collaborative infrastructure.
LIFE
What is one interesting thing about you that nobody would guess?
Outside the laboratory, I write fiction, often exploring illness, memory, stigma, and the human experiences that sit behind medicine. My story The Time of the Stopped Clock recently won the Paulette and Jay Mehta Award in Creative Writing, and my earlier story, The Forsaken Thread, received an honorable mention the previous year. Writing gives me a way to explore parts of illness and medicine that do not fit neatly into a dataset.
What is one unexpected way that your location opened an opportunity for you?
One unexpected opportunity in Little Rock has been having both my laboratory and office embedded within the Arkansas Children’s Research Institute. Working in a pediatric research environment every day shifted my broader background in cancer epigenetics toward questions directly relevant to childhood leukemia and created natural opportunities to interact with pediatric investigators and clinicians. That setting helped shape the disease focus of my laboratory and keeps the questions we ask closely connected to the clinical realities of pediatric cancer.
Biography
Samrat Roy Choudhury, PhD, is an Assistant Professor in the Department of Pediatrics at the University of Arkansas for Medical Sciences and leads a research laboratory at Arkansas Children’s Research Institute. He received his PhD in Biotechnology from the University of Calcutta, India, and subsequently completed postdoctoral training in biological engineering at Purdue University. At Purdue, he developed and applied optogenetic and CRISPR-based approaches for locus-specific epigenome editing, including targeted manipulation of DNA methylation. He later joined the Division of Hematology and Oncology at UAMS, where he extended this work into cancer epigenomics, studying how DNA methylation and chromatin states regulate aberrant gene expression in multiple myeloma.
Dr. Roy Choudhury established his independent laboratory in 2020, where his research now focuses on fusion-driven acute myeloid leukemia. His group investigates how oncogenic fusions reshape transcriptional and epigenetic programs and create dependencies that can be therapeutically exploited. A major focus is CBFA2T3–GLIS2-positive pediatric AML, where the laboratory studies enhancer-associated DNA methylation and chromatin regulation. The laboratory also studies KMT2A-rearranged AML, with emphasis on therapeutically tractable signaling and transcriptional dependencies that persist in resistant disease. His long-term goal is to translate the biology of rare, high-risk fusion-driven leukemias into more precise therapeutic strategies.