2017

Glenn Foundation for Medical Research and AFAR Grants for Junior Faculty


Sergei Doulatov, PhD

Assistant Professor, University of Washington

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.

More 2017 Recipients of this Grant

Luis Batista, PhD

The impact of progressive telomere shortening on mitochondria function and energy metabolism of human stem cells

Peter Douglas, PhD

Stress-mediated actin phosphorylation in endocytosis and age regulation

Michael Garratt, PhD

Sensory perception of the social environment: regulation of mouse development, metabolism and aging

Vyacheslav Labunskyy, PhD

Endoplasmic Reticulum (ER) stress resistance and longevity

Darcie Moore, PhD

The molecular mechanisms underlying asymmetric segregation of aging factors in mammalian neural stem cells

Vittorio Sebastiano, PhD

Transient reprogramming for efficient cell-autonomous reversal of age-associated phenotypes

Archana Unnikrishnan, PhD

Role of DNA methylation in Dietary Restriction mediated insulin sensitivity

Rui Xiao, PhD

Cold-Shock Proteins (CSPs) in stress response and lifespan modulation

Amir Zarrinpar, MD, PhD

The relationship of gut luminal dynamics and aging-related circadian dysfunction and dysmetabolism