Review: Trends Endocrinol Metab, coauth.: W.Wahli

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Increased hepatic gluconeogenesis and type 2 diabetes mellitus

Emma Barroso 1, Javier Jurado-Aguilar 1, Walter Wahli 2, Xavier Palomer 1, Manuel Vázquez-Carrera 3

. 2024 Dec;35(12):1062-1077.

Abstract

Abnormally increased hepatic gluconeogenesis is a significant contributor to hyperglycemia in the fasting state in patients with type 2 diabetes mellitus (T2DM) due to insulin resistance. Metformin, the most prescribed drug for the treatment of T2DM, is believed to exert its effect mainly by reducing hepatic gluconeogenesis. Here, we discuss how increased hepatic gluconeogenesis contributes to T2DM and we review newly revealed mechanisms underlying the attenuation of gluconeogenesis by metformin. In addition, we analyze the recent findings on new determinants involved in the regulation of gluconeogenesis, which might ultimately lead to the identification of novel and targeted treatment strategies for T2DM.

FASEB J, group Michalik

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Transcriptional and functional regulation of cell cycle and UV response by PPARβ in human skin epidermal cells

Thanh Nhan Nguyen 1, Carine Winkler 1, Stefanie Ginster 1, Stéphanie Claudinot 1, Liliane Michalik 1, Paris Jafari 1

. 2024 Dec 15;38(23):e70212.

Abstract

Solar radiation is the main source of human exposure to UV rays, which is the major carcinogen in skin cancers by inducing DNA damage. Skin cells repair these damages by activating the DNA damage response (DDR) to safeguard genome integrity, thereby preventing skin cancers. Peroxisome proliferator-activated receptor beta (PPARβ), a druggable transcription factor, is involved in the development of UV-dependent skin cancers, although its role is not mechanistically elucidated. We showed previously that PPARβ knockout (KO) mice are less prone to UV-induced skin cancers. Here, we report that PPARβ directly regulates gene expression programs associated with cell cycle and DNA repair pathways in normal human epidermal keratinocytes (NHEK). The loss of function of PPARβ in human keratinocytes led to a downregulation in the expression of key cell cycle regulators, including cyclins and cyclin-dependent kinases (CDKs). Simultaneously, it upregulated the expression of p21 protein, a known CDK inhibitor. These molecular alterations resulted in a significant reduction in cell proliferation and induced cell cycle arrest at the G2/M phase. Moreover, the absence of functional PPARβ disrupted the expression and activation of the ataxia telangiectasia and Rad3-related (ATR) pathway, a critical component of the cellular response to UV-induced DNA damage. The alterations in the ATR pathway likely contributed to an increased apoptotic response of NHEK to UV radiation. Using a mouse melanoma model, we demonstrated that the depletion of PPARβ decreases tumorigenicity of melanoma cells and delays tumor formation. Our data suggest that PPARβ inhibition could be considered as a therapeutic target for the prevention of UV-induced skin cancers, by regulating cell proliferation, attenuating DDR, and eliminating skin cells with high UV-induced mutational burden.

Welcome Melvin Poirier !

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Hello, my name is Melvin POIRIER. I am honored to join Professor Lluis Fajas’ laboratory as an intern to complete my Master’s degree in Health Biology at the University of Tours in France. Before this Master’s program, I obtained a Bachelor’s degree in health Biology with a specialization in Neuroscience. This academic and personal journey has allowed me to discover a real interest in neuroscience and reproductive biology. I am therefore fortunate to have the opportunity to work at the CIG on fertility.

On the side, I have a true passion for hiking and canicross

Welcome Manon Agostini !

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Hello ! My name is Manon Agostini, and I am excited to join Pr. Gatfield’s team for a six-month internship, working on Lisa Bertrand’s project. My research will focus on the process of re-initiation and the involvement of specific factors in this mechanism.

I am originally from Paris. I first did my Bachelor’s degree in Health Biology at the University of Paris-Est Créteil. During this time, I completed an internship at the GLY-CRRET laboratory, studying the role of glycosaminoglycans in osteoarthritis. I then pursued the first year of my Master’s degree at the University of Paris-Saclay, specializing in Genetics, Cell Biology, and Molecular Biology. There, I had the opportunity to do an internship at the NeuroPSI laboratory, where I studied the circadian rhythms of Drosophila larvae.

Currently, I am in the second year of my Master’s program at Sorbonne University, specializing in RNA Genetics and Biochemistry. My goal is to further specialize in the regulation of genome expression by non-coding RNA. Outside of academics, I enjoy drawing, painting, and art in general, as well as hiking and discovering new places. I am thrilled to be part of this team and to contribute to this project. I look forward to meeting and collaborating with everyone !

Welcome to Olivier Messina

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Hi, everyone! I am Olivier Messina, a French biologist with an interest in understanding the relationship between 3D genome organization and transcription. I completed my PhD in Marcelo Nollmann’s lab in Montpellier, France (2019–2024), focusing on the fascinating field of chromatin architecture. During my doctoral research, I contributed to the development of HiM, a microscopy technique designed to trace chromatin architecture across different cell types. I applied HiM to investigate chromatin folding, particularly the communication between cis-regulatory elements in the regulation of gene expression during early Drosophila embryogenesis and in the Drosophila brain. Additionally, I adapted HiM in combination with sophisticated bioinformatics methods to explore chromosome architecture and transcription at the single-cell level in mouse and human tissues. 

I joined Maria Cristina Gambetta’s lab in January 2025 as a postdoctoral researcher, where I will be studying the regulatory role of long-range chromatin interactions between promoter pairs in fully differentiated Drosophila neurons using microscopy- and sequencing-based methods (Hi-C, Micro-C).

Welcome Mira Brazane !

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“Mira obtained her bachelor and later Masters in microbiology from the university of Bejaia in Algeria. She moved to France where she specialized in molecular and cell biology following a masters at Sorbonne université in Paris. She then did a four year PhD under the supervision of Pr. Clément Carré at Sorbonne Université. She studied the molecular functions of the RNA methyltransferase FTSJ1 in gene regulation and neural development. Mira joined the Roignant group in January 2025 to study the dynamics and functions of RNA methylation in Drosophila melanogaster.”