Alexander Jais
Groupleader of the Junior Research Group "Diet-Induced Metabolic Alterations"Academic Career
During his PhD research, Dr. Alexander Jais identified the enzyme heme oxygenase-1 (HO-1) as a strong positive predictor of metabolic disease by intersecting patient data with genetic evidence from five tissue-specific HO-1 deletion mouse models (Jais et al., Cell 2014). His research identified a novel pathomechanism in obesity-induced inflammation, and these results have substantial implications for the stratification of healthy and unhealthy obesity, highlighting the prognostic value of HO-1 for detecting early disease onset. During his postdoctoral research, he revealed that HFD feeding suppresses glucose transporter (GLUT)-1 expression in vascular endothelial cells of the blood-brain barrier, evoking a compensatory recruitment of endothelial-associated macrophages to release VEGF to counteract downregulated GLUT-1 expression (Jais et al., Cell 2016). These findings suggest that metabolic inflammation may develop as a compensatory mechanism to restore transiently reduced brain glucose availability upon consumption of a hypercaloric palatable HFD. Furthermore, he demonstrated that prepronociceptin (PNOC)-expressing neurons in the ARC are activated upon HFD consumption to promote hyperphagia, making them an attractive target for the treatment of obesity and associated metabolic diseases (Jais et al., Neuron 2020).
During his PhD and postdoctoral research, Dr. Jais also participated in highly collaborative projects that led to groundbreaking discoveries, such as the identification of the anaplastic lymphoma kinase (ALK) as a thinness gene and the characterization of a critical role for the enzyme cofactor tetrahydrobiopterin (BH4) in T cell biology (Orthofer et al., Cell 2020; Cronin et al., Nature 2018).
Research Areas and Expertise
Neurobiology and Metabolic Research
Dr. Jais specializes in the intersection of neurobiology, metabolism, and immunometabolism, with a strong focus on how the central nervous system (CNS) regulates energy homeostasis. His research seeks to uncover the neural mechanisms that govern the brain's interpretation and integration of nutritional, hormonal, and sensory signals to control feeding behavior, energy expenditure, and glucose metabolism.
Utilizing advanced techniques such as chemogenetics, optogenetics, in vivo imaging, and single-cell transcriptomics, Dr. Jais examines the structure and function of specific neuronal populations activated by palatable, energy-dense foods. Furthermore, his work investigates how chronic overnutrition can lead to maladaptive remodeling of these neurocircuits, contributing to obesity and related metabolic disorders.
Important Career Steps
Principal Investigator
Principal Investigator of the Helmholtz Young Investigator Group "Diet-Induced Metabolic Alterations" at the Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, based at the University of Leipzig
Postdoctoral Fellow
Postdoctoral Fellowship at the Max Planck Institute for Metabolism Research in Cologne, Germany, in the laboratory of Prof. Jens Brüning, focusing on the neuronal control of metabolism
Doctoral Researcher
Doctoral Researcher at the Medical University of Vienna under the supervision of Dr. Harald Esterbauer, Department of Laboratory Medicine, focusing on the molecular mechanisms of metabolic inflammation
Honors and Awards
EFSD / Novo Nordisk Foundation Future Leaders Programm
2022Award of Excellence
Austrian Federal Ministry of
Science Research and Economy
2014Sanofi-Aventis Prize
Sanovi-Aventis, Austria
2014
Newest publication
See all2025 Cell Reports
Short-term transition to high-fat diet (HFD) feeding causes rapid changes in the molecular architecture of the blood-brain barrier (BBB), BBB permeability, and brain glucose uptake. However, the precise mechanisms responsible for these changes remain elusive. Here, we detect a rapid downregulation of Notch signaling after short-term HFD feeding. Conversely, Notch activation restores HFD-fed mouse serum-induced reduction of Glut1 expression and glycolysis in cultured brain microvascular endothelial cells (BMECs). Selective, inducible expression of the Notch intracellular domain (IC) in BMECs prevents HFD-induced reduction of Glut1 expression and hypothalamic glucose uptake. Caveolin (Cav)-1 expression in BMECs is increased upon short-term HFD feeding. However, NotchICBMECs mice display reduced caveola formation and BBB permeability. This ultimately translates into reduced hypothalamic insulin transport, action, and systemic insulin sensitivity. Collectively, we highlight a critical role of Notch signaling in the pleiotropic effects of short-term dietary transitions on BBB functionality.