Sergei Doulatov, Ph.D.

Doulatov lab seeks to understand how genetic alterations in normal hematopoietic stem cells (HSCs) drive the development of myeloid neoplasms, including myelodysplastic syndromes (MDS) and acute leukemias. We are interested in understanding the importance of order and sequence of premalignant somatic mutations and their impact on HSC differentiation and self-renewal. We utilize primary human cells and induced pluripotent stem cells (iPSCs) to create powerful models of hematological disorders (Doulatov et al. Sci Transl Med 2017). iPSCs are generated by reprogramming of MDS and AML patient samples, becoming a source of patient-specific HSCs. By combining reprogramming with genome sequencing and gene editing, we aim to reconstruct how pathogenic mutations cooperate to drive malignant transformation and develop new therapeutic interventions.

We are also interested in the biology of normal human hematopoiesis and erythropoiesis, with the focus on autophagy and mitophagy, key metabolic pathways for recycling damaged cellular components implicated in stem cell function and aging. Current goals involve understanding the role of autophagy in different hematopoietic cell types, defining cell-type specific molecular regulators of autophagy and mitophagy, and development of autophagy therapeutics.