Thom Lab Research Overview

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The Thom Lab aims to use human genetics data, from population-level genome-wide association studies to single cell analyses to discover novel genomic regions and genes that impact hematopoiesis. We are keen to incorporate iPSC-based data to tailor our genomics strategies on in vitro hematopoietic biology. Objectives include constructing blood trait-specific prediction models using machine learning techniques; using genetic colocalization strategies to pinpoint genomic loci and genes governing blood and disease traits; and using Mendelian randomization strategies to explain relationships between blood and disease traits.

Regulation of actin cytoskeletal dynamics is critical to many important cellular processes. Hematopoietic progenitor cells are derived from specialized hemogenic endothelial cells during in vitro and in vivo development. We aim to define the role of tropomyosins, particularly Tropomyosin 1, during formation of hematopoietic progenitor cells, red blood cells, and platelets using induced pluripotent stem cell and conditional animal models. Since tropomyosins are key actin regulatory molecules, we anticipate these models will reveal novel insights into the role of actin biology during these cellular transitions.

There are stark contrasts between platelets and other blood cells in neonates, as compared with older children and adults. These differences are clinically important, since blood products donated by adults are routinely transfused into neonates. We aim to reveal mechanisms governing neonatal hematopoiesis and understand differences in blood cell functions through single cell analysis of murine models and ex vivo human tissues with goals to understand why infant blood cells are so different, and to better anticipate and mitigate complications associated with current transfusion practices.