I completed my Ph.D. in 2012, a joint project of Medical School of University of Patras and National Institute of Medical Research (current Francis Crick Institute) at London. I studied the role of the cell cycle regulator Geminin in T cell differentiation and hemopoietic system development using conditional knock-out in vivo models, microarrays gene expression, and ChIP, to understand molecular mechanisms regulating proliferation and cell fate decisions. My Ph.D. research, which led to publications in Journal of Immunology, Cell Cycle, and Development, further raised my interest in basic molecular mechanisms that guide the differentiation of normal hemopoietic cells and on how deregulation of these mechanisms lead to hematological diseases.
I consequently joined Professor Vyas group as a postdoctoral scientist to study and further understand how hemopoietic stem and progenitor cells loose potentiality and differentiate during hemopoiesis in human. In parallel the access in one of the largest collections of Acute Myeloid Leukemia (AML) patient samples allowed me to characterize heterogeneous progenitor populations in AML.
In normal human hemopoiesis, multiple progenitor populations produce lymphoid and myeloid cells. We demonstrated that there are at least three functionally and transcriptionally distinct lympho-myeloid progenitor populations (LMPP, MLP and GMP) at the clonal level. By combining state-of-the art FACS sorting, single cell functional assays and single-cell RNA sequencing analysis we have shown that the majority of the progenitors have uni-lineage myeloid or lymphoid potential with rarer bi- and multi-lineage progenitors present within the heterogeneous populations of LMPP, MLP and GMP. The transcriptional heterogeneity of single LMPPs, MLPs and GMPs was also characterized at the single cell level and in total the results of this study were published in Nature Immunology.
Going forward I am interested in developing improved in vivo models that will allow us to better understand the function of normal and leukemic hemopoietic stem and progenitor cells at the single cell level as well understanding the role of different cell components of the human bone marrow microenvironment in health and disease.
A NOVEL MODEL OF HUMAN LYMPHO-MYELOID PROGENITOR HIERARCHY BASED ON SINGLE CELL FUNCTIONAL AND TRANSCRIPTIONAL ANALYSIS
Karamitros D. et al, (2017), HAEMATOLOGICA, 102, 20 - 20
Concise Review: Geminin-A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells.
Patmanidi AL. et al, (2017), Stem Cells, 35, 299 - 310
Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage.
Quek L. et al, (2016), J Exp Med, 213, 1513 - 1535
Whole transcriptome data analysis of mouse embryonic hematopoietic stem and progenitor cells that lack Geminin expression.
Patmanidi AL. et al, (2016), Data Brief, 7, 889 - 893
CLONAL STRUCTURES OF LEUKAEMIA STEM CELL POPULATIONS IN MYELOID BLAST PHASE CHRONIC MYELOID LEUKAEMIA
Karamitros D. et al, (2016), HAEMATOLOGICA, 101, 234 - 235