Sergei Doulatov
Sergei Doulatov - PhD
AFAR Research Grants for Junior Faculty - 2017
Sergei Doulatov

Sergei Doulatov - PhD

Assistant Professor - University of Washington
Washington, USA


AFAR Research Grants for Junior Faculty - 2017

The role of autophagy in human hematopoietic stem cell aging

Blood production is maintained by hematopoietic stem cells (HSCs), or blood stem cells. But the regenerative potential of HSCs declines with age, leading to an increased incidence of blood disorders such as myelodysplastic syndromes and leukemias.

Dr. Doulatov believes that one of the pathways maintaining the health of HSCs and other types of stem cells is autophagy, the digestion of cellular parts by enzymes of the same cell. Autophagy is responsible for degrading and recycling damaged macromolecules and organelles, and is thought to be a key metabolic pathway in lifespan extension.

Dr. Doulatov hypothesizes that during aging, HSCs need autophagy to recycle damaged organelles. Therefore, stimulating autophagy can rejuvenate aged stem cells. He and his team found a small molecule called SMER28 that can stimulate autophagy. The team will inactivate key autophagy genes in young and older HSCs, then test the genes’ function by transplanting them into special strains of mice (models for human bone marrow transplantation). They predict that HSCs from older donors will fail to transplant if they turn down autophagy.

The team will then use genetic methods and small molecules such as SMER28 to turn up the levels of autophagy in these older HSCs. Dr. Doulatov predicts that old HSCs will be “rejuvenated” after transplant. Even if the effect is temporary, it could still be valuable for older patients who donate or receive marrow transplants, and would open the possibility of staving off age-related decline in other tissues.

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