Abstract

Dynamic adaptability of the vascularendothelium in health and disease

Aquiescent, resilient layer of blood vessel-lining endothelial cells (ECs) isvital for maintaining organ function and enabling healthy aging. Much has beenlearnt in recent years about the mechanisms controlling the resilient ECphenotype and how its dysregulation results in disease initiation. Yet, little is known if and how mechanisms of vascular resilience are affected byenvironmental rhythmic stimuli (extrinsic (e.g., light-dark, feeding-fasting)or intrinsic (e.g., blood pressure, hematopoiesis)). Performing day/night analyses of organotypically differentiated ECs, we identified distinctorgan-specific time-of-the-day dependent transcriptomic programs of resting ECsin adult mice. These translate functionally into temporal vascular adaptationsduring the day that critically sustain steady-state tissue health and function. Our ongoing work with EC-specific clock gene targeting infers circadian determinants of vascular health in liver physiology.

Short Bio

Dr.Mahak Singhal is a Junior Research Group Leader at the European Center for Angioscience (ECAS), part of the Medical Faculty at Heidelberg University. Dr. Singhal completed his Ph.D. in Biosciences at Heidelberg University and DKFZ, under the supervision of Hellmut Augustin. His doctoral research focused on how blood and lymphatic vessels interact with tumor cells. His research earned him the Helmholtz Doctoral Prizein 2020 for outstanding research in health sciences across all Helmholtzcenters in Germany. After a brief postdoctoral fellowship, he established his independent junior research group at ECAS in 2022. His research group explores how endothelial cells sense and respond to environmental and circadian cues. Dr. Singhal was awarded a 2025 European Research Council (ERC)Starting Grant, funding for his project on vascular rhythms and their impact on organismal health.

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