The focus of our lab is to understand how disruptions of the circadian system, such as in shift work, leads to disease. We are particularly interested in metabolic and mental co-morbidity as we believe circadian malfunction is a common denominator linking these health problems.
Like most other living organisms, humans have evolved to function in harmony with the day/night cycles. The biological processes following a ̴24-hour cycle are termed circadian (from the latin words Circa=about and Diem=day). Circadian rhythms are controlled by a genetically encoded “molecular clock” that exists in every nucleated cell and thus, in every organ. At its core, the molecular clock consists of a transcriptional-translational feedback loop regulating the rhythmic expression of thousands of genes. The clock in different tissues forms a network that communicates to align bodily functions with the time of day. Circadian disruption is caused by untimely light exposure, food intake and stress. Modern societies exist with artificial light at night, 24-hour access to hypercaloric foods and chronic stress.
Our research focuses on understanding how environmental factors are integrated by the circadian system in specific organs and subsequently influencing rhythms in distant tissues. Circadian inter-organ communication involves several processes including metabolic signaling. The central clock is the main driver of systemic metabolic rhythms by controlling appetite and energy expenditure while the clocks in metabolically active organs, such as the liver and fat tissue, contribute to regulate metabolic rhythms by integrating nutritional cues.
The circadian clock is tightly coupled with metabolism, as specific metabolites act as substrates and co-substrates for epigenetic regulators; factors changing the DNA structure without changing the sequence. Hence, circadian metabolic signaling from one organ can control rhythmic gene expression in a distant tissue. Thus, different tissue clocks cooperate to align behavioral and physiological rhythms to the time of day. Our project aims to delineate these mechanisms and how they relate to metabolic and mental health.
An overview of the research program
Paul Petrus did his PhD at Karolinska Institutet studying metabolism and adipose tissue biology. After his PhD defense he pursued a Postdoc in Chronobilogy at University of California, Irvine (UCI) between 2019-2022. Paul moved back to Karolinska Institutet in 2022 and started his own group focusing on circadian biology.
As postdoctoral researcher in the Petrus lab, Santiago Cortasa studies the effects of peripheral metabolic rhythms on hypothalamic function and behavior.
Santiago graduated from Favaloro University in Biological Sciences in 2015 with his thesis on learning and memory, testing the parameters of Contextual Pavlovian Conditioning. He worked at Maimonides University from 2016 to 2022 on his doctoral thesis in Reproductive Neuroendocrinology. During his PhD, Santiago was able to determine the interaction of prolactin with different tissues such as the hypothalamus, the pituitary gland and the ovaries.
As a postdoctoral researcher in the Petrus lab, Christina Savva joined studies the effects of stress on circadian regulation of metabolism.
Christina obtained her PhD at Karolinska Institutet from the Department of Medicine, Huddinge (MedH), where she studied the effects of maternal obesity on offspring metabolism with focus on sex differences in liver and adipose tissue. Previously, she completed a Master’s thesis at MedH, where she studied the estrogen receptor beta regulation of lipid homeostasis in female and male mice.
Ivan Vlassakev's research is primarily focused on circadian regulation of adipose tissue and liver crosstalk.
Ivan is a MSc Nutritional Sciences graduate student with experience in the research areas of human physiology, metabolism, and circadian rhythms. His hobbies are skiing, gym, and football. He also is a helicopter pilot.
- Novo Nordisk foundation
- The Wenner-Gren foundations
- Åke Wiberg foundation
Tryptophan metabolism is a physiological integrator regulating circadian rhythms.
Petrus P, Cervantes M, Samad M, Sato T, Chao A, Sato S, Koronowski KB, Park G, Alam Y, Mejhert N, Seldin MM, Monroy Kuhn JM, Dyar KA, Lutter D, Baldi P, Kaiser P, Jang C, Sassone-Corsi P
Mol Metab 2022 10;64():101556
The central clock suffices to drive the majority of circulatory metabolic rhythms.
Petrus P, Smith JG, Koronowski KB, Chen S, Sato T, Greco CM, Mortimer T, Welz PS, Zinna VM, Shimaji K, Cervantes M, Punzo D, Baldi P, Muñoz-Cánoves P, Sassone-Corsi P, Benitah SA
Sci Adv 2022 07;8(26):eabo2896
Antibiotic-induced microbiome depletion remodels daily metabolic cycles in the brain.
Smith JG, Sato T, Shimaji K, Koronowski KB, Petrus P, Cervantes M, Kinouchi K, Lutter D, Dyar KA, Sassone-Corsi P
Life Sci 2022 Aug;303():120601
Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms.
Greco CM, Koronowski KB, Smith JG, Shi J, Kunderfranco P, Carriero R, Chen S, Samad M, Welz PS, Zinna VM, Mortimer T, Chun SK, Shimaji K, Sato T, Petrus P, Kumar A, Vaca-Dempere M, Deryagin O, Van C, Kuhn JMM, Lutter D, Seldin MM, Masri S, Li W, Baldi P, Dyar KA, Muñoz-Cánoves P, Benitah SA, Sassone-Corsi P
Sci Adv 2021 Sep;7(39):eabi7828
Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.
Petrus P, Lecoutre S, Dollet L, Wiel C, Sulen A, Gao H, Tavira B, Laurencikiene J, Rooyackers O, Checa A, Douagi I, Wheelock CE, Arner P, McCarthy M, Bergo MO, Edgar L, Choudhury RP, Aouadi M, Krook A, Rydén M
Cell Metab 2020 02;31(2):375-390.e11
Transgenerational Epigenetic Mechanisms in Adipose Tissue Development.
Lecoutre S, Petrus P, Rydén M, Breton C
Trends Endocrinol Metab 2018 10;29(10):675-685
Adipocyte Expression of SLC19A1 Links DNA Hypermethylation to Adipose Tissue Inflammation and Insulin Resistance.
Petrus P, Bialesova L, Checa A, Kerr A, Naz S, Bäckdahl J, Gracia A, Toft S, Dahlman-Wright K, Hedén P, Dahlman I, Wheelock CE, Arner P, Mejhert N, Gao H, Rydén M
J Clin Endocrinol Metab 2018 02;103(2):710-721