Cancelas Lab Research

The Cancelas Lab has been instrumental in elucidating the cellular and molecular mechanisms of hematopoietic cells, focusing on the Rho family of GTPases in health and disease. The team has provided critical insights into physiological cell-autonomous and microenvironment/cytokine signaling mechanisms, as well as metabolic and mitochondrial-dependent processes in myeloid progenitor migration and bone marrow retention. Their key findings have been published in high-impact journals (Gu Y et al., Science 2003; Cancelas JA et al., Nat. Med. 2005; Sengupta A et al., PNAS 2011; Gonzalez-Nieto D et al., Blood 2012; Taniguchi-Ishikawa et al., Nature Comm. 2013; Chang KH et al., Cell Reports 2014).

The lab has also defined mechanisms regulating oncogenic tyrosine kinase signals in leukemic progenitors, uncovering both intrinsic and microenvironment-dependent pathways through Rho GTPases (Yamada Y et al., Blood 2006; Thomas EK et al., Cancer Cell 2007; Kesarwani M et al., Nat. Med. 2017; Hegde S et al., Leukemia 2021).

Through the study of hematopoietic differentiation of human iPSCs from patients with Severe Congenital Neutropenia (SCN), the lab revealed pathogenetic mechanisms of neutropenia linked to ELANE mutations. These studies demonstrated the role of neutrophil elastase mislocalization, ER stress, and apoptosis, alongside non-cell-autonomous effects leading to monocytosis (Tidwell T et al., Blood 2014; Nayak RC et al., JCI 2015). The team has also pioneered methods for characterizing iPSCs and optimized cryopreservation and delivery techniques for functional lymphocyte populations (Salomonis N et al., Stem Cell Reports 2016; Daily K et al., Scientific Data 2017).

The translational research group has optimized methods for progenitor and granulocyte transfusions in neutropenic patients, validated platelet and red cell storage methods in clinical trials, and developed strategies to prevent cold storage platelet damage (Cancelas JA et al., Transfusion 2014, 2022; Slichter S et al., Transfusion 2018). The team has generated first-in-human clinical data for various biological therapies and continues to explore innovative solutions for blood product storage and lyophilized platelets (Ohanian M, Cancelas JA et al., Am. J. Hematol. 2021).