Deciphering the molecular mechanisms underlying human evolutionary adaptation to hypoxia

Multicellular organisms critically rely on systems such as red blood cell production (erythropoiesis) to sense oxygen availability and ensure a continuous systemic supply.

Yet, the precise underlying molecular mechanisms and their regulatory dynamics are not well understood.In this project, I will use the lens of human evolution to decipher gene regulatory networks that govern cellular systems functions responsible for Tibetan adaptation to high-altitude hypoxia.

This low oxygen environment poses extreme challenges to human physiology, yet Tibetans have genetically adapted and show increased fitness compared to non-adapted neighbours.

Investigating this natural experiment can shed light onto fundamental mechanisms regulating biological processes that control oxygen homeostasis.

To this end, I will develop a novel interdisciplinary approach using human kidney organoids to model erythropoiesis regulation in genetically adapted backgrounds and apply state of the art genome engineering and single cell high resolution technologies as readouts.

This innovative interdisciplinary approach will elucidate the genetic and regulatory mechanisms that are fundamental in hypoxia physiology.

New insights may shed light on medically relevant hypoxia and the next generation of regenerative medicinal approaches to better human health.