Projects
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How do tropomyosins regulate hematopoiesis?
Our recent work employed machine learning algorithms to identify novel blood trait-regulatory sites from human GWAS data, including SNPs in the TPM1 gene locus.
People with this polymorphism express less TPM1 and have higher platelet counts.
We used genome-edited iPSCs and mouse models to confirm that TPM1 normally constrains in vitro hematopoiesis. Ongoing work aims to define mechanisms responsible for this effect as well as additional cell types affected by TPM1 loss.
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Can we leverage human genetics data to discern cell-intrinsic vs extrinsice regulatory factors?
Blood cell development relies on cell-intrinsic gene programs, and also responds to external stimuli. Human GWAS data alone cannot distinguish between intrinsic and extrinsic factors.
We use statistical genetics, including colocalization and Mendelian randomization approaches, to define cells and factors that regulate hematopoiesis and other human traits.
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Can we define blood trait-disease relationships and pathophysiology using human genetic data?
Platelets and other blood cells impact complex disease. In turn, systemic disease can alter blood cell development and function.
We use a combination of human genetics and cellular systems to define genes and mechanisms that dictate these trait relationships.
Current and future projects
We have open positions for graduate students, fellows, and post-docs!
Training machine learning algorithms to recognize blood trait-specific epigenetic signals and regulatory genomic loci.
Expanding Mendelian randomization and genetic colocalization pipelines to understand blood trait-disease links
Developing single cell analyses to define hematopoietic pathways in iPSCs and human tissues.
Developing in vivo and in vitro models to explore how tropomyosins and actin regulate blood cell formation, differentiation, and function