Research Projects
Genetic variation rarely influences a single phenotype. Instead, inherited variants often exert pleiotropic effects, shaping multiple traits through both shared and distinct molecular and cellular mechanisms. Our laboratory seeks to understand how hematopoietic function serves as a central biological conduit through which genetic variation influences diverse physiological processes and disease outcomes.
Through hematopoiesis, hematopoietic stem cells (HSCs) continuously regenerate the blood system, producing more than 100 billion blood cells each day to maintain immune surveillance, tissue homeostasis, and systemic communication between organs. We hypothesize that pleiotropic genetic variation establishes hematopoietic states that influence immune function, metabolism, cardiovascular biology, and neurocognitive function, thereby linking multiple complex human traits and diseases. Importantly, these relationships are bidirectional, whereby physiological and disease states also remodel hematopoietic function, creating dynamic feedback between the hematopoietic system and peripheral organs throughout life. This reciprocal communication is particularly evident in neuroimmune interactions, through which the hematopoietic and nervous systems continuously influence one another to regulate normal physiology and disease susceptibility.
We integrate population-scale human genetics, single-cell genomics, multi-omic profiling, and functional experimental models to define the molecular and cellular mechanisms linking hematopoietic function to health and disease.
Our primary disease focus is type 1 diabetes (T1D), an autoimmune disease that exemplifies this systems-level biology. Beyond autoimmune destruction of pancreatic β-cells, T1D is frequently accompanied by alterations in blood cell traits, metabolic dysfunction, cardiovascular complications, and changes in neurocognitive function. We use T1D as a model system to understand how hematopoietic function contributes not only to disease susceptibility but also to the broader constellation of physiological changes, disease comorbidity, and long-term complications.
Our ultimate goal is to establish a systems-level framework in which hematopoietic function integrates genetic variation with environmental and physiological signals to shape human health across multiple organ systems. By identifying the molecular and cellular mechanisms that underlie genetic pleiotropy, we aim to uncover therapeutic strategies that transcend traditional disease boundaries and advance precision medicine.