Rodriguez Fraticelli, Alejo E
ICREA Research Professor at Institut de Recerca Biomèdica (IRB Barcelona).
Life & Medical Sciences
Short biography
Research interests
Hematopoiesis has long been modeled as a stepwise hierarchical process, where all blood cells arise from a single group of rare multipotent hematopoietic stem cells (HSCs). In the past 5 years, I have made major contributions that have challenged this paradigm, revealing an extensive heterogeneity among individual HSCs and the differentiation trajectories that they undertake. My lab is interested in uncovering the determinants of this variation, and their consequences for human disease.
To study functional heterogeneity in stem cells, I developed a variety of genetic tools that allow the simultaneous recording of the progeny of thousands of single stem/progenitor cells (i.e. their single-cell lineages) in vivo, at unprecedented resolution (Rodriguez-Fraticelli et al. Nature 2018). My results highlighted the remarkable differences between stem cell behaviors in situ. This was a paradigm-shifting study that prompted a completely new view of blood cell hierarchies in the field (Laurenti et al. Nature 2018).
More recently, I have been developing new methods to read out recorded lineages using single-cell profiling approaches. This analysis resulted in a series of ground-breaking discoveries in the field of hematopoiesis. Strikingly I identified specific gene programs that determine stem cell fates, but these transcriptional programs are insufficient to fully predict stem cell behavior on their own (Rodriguez-Fraticelli et al. Nature 2020; Weinreb*, Rodriguez-Fraticelli* et al. Science 2020; Bowling et al. Cell 2020).
Since joining IRB Barcelona, my lab has been applying these technologies to understand how differences in stem cell self-renewal behaviors influence their response to leukemic mutations and aging. We are currently writing two different manuscripts based on these findings (Quach et al. and Singh et al.). I have presented these findings at a recent conference (FASEB Meeting 2021) and received invitations to submit from editors of top journals in the field.