This week we profile a recent publication in Cell Stem Cell from Dr. Andreea Reilly (pictured, right) and the laboratory of Dr. Sergei Doulatov (left) at UW and the Institute for Stem Cell and Regenerative Medicine.
Can you provide a brief overview of your lab’s current research focus?
My lab at the University of Washington investigates the genetic basis of clonal progression from normal hematopoietic stem cells (HSCs) to premalignant and malignant hematopoiesis. We use iPSCs and primary HSCs to develop human cell models of myelodysplastic syndromes and myeloid leukemias. Our recent focus has been on mechanisms by which spliceosome mutations alter hematopoiesis, and the role of 5q deletions/lamin B1 in progression from normal HSCs to high-risk leukemias.
What is the significance of the findings in this publication?
Abnormal nuclear morphology is a hallmark of most cancers, widely used in cancer diagnosis. In our paper we discover that aberrant nuclear shape in blood cancers is caused by deletion of a gene called lamin B1. Lamins are proteins that line the inside of the nucleus, and are mutated in inherited disorders, such as progeria. We show that lamin B1 deletion causes changes in stem cell function, nuclear shape, and leukemia progression. Our paper discovers that the lamin B1 gene is responsible for the abnormal nuclei that have puzzled and helped pathologists recognize cancers over the past century. It also shows that the presence of nuclear changes may be an early biomarker of blood cancers, which may allow for earlier diagnosis and treatment of leukemias.
What are the next steps for this research?
We are pursuing a lot of exciting directions. We want to understand how lamin B1 loss contributes to the evolution of a very aggressive type of leukemia marked by widespread chromosomal abnormalities. We also want to know the mechanisms by which lamin B1 regulates HSC fate and lineage commitment, which we think involves very fine changes in chromatin organization. Lastly, we are curious about the interplay between nuclear shape and chromatin organization. We do have an open postdoc position, so if you are interested in this research please apply directly by sending your CV.
If you’d like us to mention your funding sources, please list them.
First and foremost, I will acknowledge the two amazing postdocs: Andreea Reilly who drove this project with the help from J. Philip Creamer. I would especially like to thank the DP2 award from the NIH Common Fund, and the Kuni Foundation for their generous support which gave us the freedom to explore these exciting ideas.
