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The Nakada Lab studies how adult stem cells maintain tissue homeostasis, respond to physiological stress, and become transformed during aging and cancer development. Our research focuses on hematopoietic stem cells (HSCs), the rare blood-forming stem cells that sustain lifelong blood production and regenerate the hematopoietic system following injury, infection, and other stressors. We seek to understand how stem cells adapt to changing environments and how these adaptive programs influence health and disease.

A central goal of our laboratory is to define the molecular mechanisms that regulate stem cell self-renewal, differentiation, and fitness. Using mouse genetics, genome engineering, functional genomics, and epigenomic approaches, we investigate how metabolic pathways, environmental factors, and cellular signaling networks shape stem cell behavior across the lifespan.

One major focus of our research is clonal hematopoiesis, an age-associated condition in which blood stem cells acquire somatic mutations that provide a competitive advantage, leading to the expansion of mutant clones. Clonal hematopoiesis is increasingly recognized as an important risk factor for hematologic malignancies and a broad range of age-related disorders. We are particularly interested in understanding how environmental and lifestyle factors, especially diet, influence the initiation and progression of clonal hematopoiesis.

Our laboratory investigates how dietary composition and metabolic state alter the fitness of mutant hematopoietic stem cells and affect clonal expansion. We seek to determine how interactions between diet, metabolism, and genetic mutations contribute to the development of clonal hematopoiesis and how these processes influence systemic metabolic diseases. By uncovering the mechanisms linking stem cell biology to whole-body metabolism, we aim to identify new strategies to prevent or slow the progression of age-related diseases.

We also study how normal mechanisms that regulate stem cell function are co-opted in leukemia to promote malignant self-renewal and block differentiation. Our long-term objective is to identify fundamental principles that distinguish healthy stem cells from disease-promoting stem cells and to leverage this knowledge to develop therapies that enhance regeneration, combat metabolic disease, and eliminate cancer.