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Thom Lab Research Overview
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.
- Thom CS, Jobaliya CD, Lorenz K, Maguire JA, Gagne A, Gadue P, French DL, Voight BF. Tropomyosin 1 genetically constrains in vitro hematopoiesis. BMC Biology. 2020. May 14;18(1): 52. PMID: 32408895
- Thom CS, Voight BF. Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes. BMC Med Genomics. 2020 Jun 29;13(1): 89. PMID: 32600345.
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.
- Thom CS, Jobaliya CD, Lorenz K, Maguire JA, Gagne A, Gadue P, French DL, Voight BF. Tropomyosin 1 genetically constrains in vitro hematopoiesis. BMC Biology. 2020 May 14;18(1): 52. PMID: 32408895
- Thom CS, Chou ST, French DL. Mechanistic and translational advances using iPSC-derived blood cells. J Exp Pathol (Wilmington). 2020 1(2): 36-44. PMID: 33768218
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.
- Thom CS, Devine M, Kleinman S, Jensen EA, Lambert MP, Padula MA. Neonatal platelet count trends during inhaled nitric oxide therapy. Br J Haematol. 2020 Feb;188(3): e28-e30. PMID: 31840227
- Thom CS, et al. Extreme thrombocytosis is associated with critical illness and young age, but not increased thrombotic risk, in hospitalized pediatric patients. JThrombo Haemost. 2020 Dec;18(12): 3352-3358. PMID: 32979018
- Thom CS, Brandsma E, Lambert MP. Thrombocytosis in an infant with a TRPV4 mutation: a case report. Platelets. 2021 Apr 3;32(3): 429-431. PMID: 32319342