AACR Hematologic Malignancies Research Fellowship

The AACR Hematologic Malignancies Research Fellowship represents an effort to encourage and support a postdoctoral or clinical research fellow to conduct basic, translational, clinical, or population sciences research projects focused on hematologic malignancies.

2025 Grantee

Sean E. Healton, MD, PhD

Fellow, Hematology and Medical Oncology
Memorial Sloan Kettering Cancer Center
New York, New York, USA
Investigating Chromatin-Based Mechanisms of B cell Epigenetic Plasticity and Lymphomagenesis

Scientific Statement of Research

Diffuse large B cell lymphomas (DLBCLs) arise from mature B cells that have acquired stem-like properties, enabling them to self-renew and adapt to therapeutic challenges, which can drive disease relapse. The linker histone H1, mutated in up to 40% of DLBCLs, normally sequesters stem cell genes within compact chromatin. H1 loss of function mutations lead to the aberrant expression of these genes, enhancing the fitness and phenotypic plasticity of germinal center B cells, thereby promoting lymphomagenesis. H1 loss results in a striking gain of H3K36me2, a histone H3 modification mediated by NSD2 and associated with open chromatin. Although the role of H3K36me2 is poorly defined, preliminary data suggest it is critical in the acquisition and maintenance of plasticity. Dr. Healton hypothesizes that H1 mutations drive stem-like plasticity through NSD2-mediated H3K36me2 and that therapeutic interference with this epigenetic axis will abrogate DLBCL plasticity, fitness, and relapse potential, substantially improving outcomes for these patients.

Biography

Dr. Healton received his undergraduate degree from Skidmore College where he graduated summa cum laude with highest honors, majoring in Chemistry with a minor in Music. He then obtained his medical and doctoral degrees from Albert Einstein College of Medicine, and studied the roles of linker histones in epigenetic regulation. After completing a residency in Internal Medicine at NYU-Langone Hospital, he began a fellowship in Medical Oncology and Hematology at Memorial Sloan Kettering Cancer Center in 2023. He sees patients in the Lymphoma Division and is conducting research at Weill-Cornell.

Acknowledgment of Support

“I am deeply honored and grateful to receive the AACR Hematologic Malignancies Research Fellowship. This award will support my research into epigenetic mechanisms of lymphomagenesis with the aim of ultimately improving outcomes for patients.”