Cyrielle Billon

• PhD
• PostDoc Position at University of Health Sciences and Pharmacy

Background Cancer creates an immunosuppressive environment that hampers immune responses, allowing tumors to grow and resist therapy. One way the immune system fights back is by inducing ferroptosis, a type of cell death, in tumor cells through CD8 ⁺ T cells. This involves lipid peroxidation and enzymes like lysophosphatidylcholine acyltransferase...

Autophagy is an essential self-degradative and recycling mechanism that maintains cellular homeostasis. Estrogen receptor-related orphan receptors (ERRs) are fundamental in regulating cardiac metabolism and function. Previously, we showed that ERR agonists improve cardiac function in models of heart failure and induce autophagy. Here, we characteri...

BACKGROUND Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are...

Physical exercise induces physiological adaptations and is effective at reducing the risk of premature death from all causes. Pharmacological exercise mimetics may be effective in the treatment of a range of diseases including obesity and metabolic syndrome. Previously, we described the development of SLU-PP-332, an agonist for the ERRa, b and g nu...

The nuclear receptor (NR) superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiological processes. In this review, we will summarize and discuss recent progress in NR biology and drug development derived from the integration of various approaches, including biophy...

Estrogen-related receptors (ERR) are an orphan nuclear receptor sub-family that play a critical role in regulating gene transcription for several physiological processes including mitochondrial function, cellular energy utilization and homeostasis. They have also been implicated to play a role in several pathological conditions. Herein, we report t...

Repetitive physical exercise induces physiological adaptations in skeletal muscle that improves exercise performance and is effective for the prevention and treatment of several diseases. Genetic evidence indicates that the orphan nuclear receptors estrogen receptor-related receptors (ERRs) play an important role in skeletal muscle exercise capacit...

Autophagy is an essential self-degradative and recycling mechanism that maintains cellular homeostasis. Estrogen receptor-related orphan receptors (ERRs) play fundamental role in regulation of cardiac metabolism and function. Previously, we showed that ERR agonists improve cardiac function in models of heart failure and induce autophagy in cardiomy...

Repetitive physical exercise induces physiological adaptations in skeletal muscle that improves exercise performance and is effective for the prevention and treatment of several diseases. Here we report the identification of a synthetic agonist for the orphan nuclear receptor ERRα (estrogen receptor-related receptor α), SLU-PP-332, that activates a...

Non-alcoholic fatty liver (NAFLD) over the past years has become a metabolic pandemic linked to a collection of metabolic diseases. The nuclear receptors ERRs, REV-ERBs, RORs, FXR, PPARs, and LXR are master regulators of metabolism and liver physiology. The characterization of these nuclear receptors and their biology has promoted the development o...

Cardiac metabolic dysfunction is a hallmark of heart failure. Estrogen related receptors ERRα and ERRγ are essential regulators for cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for heart failure. However, no natural or synthetic ERR agonist is available to demonstrate their pharmacological effect in...

Nuclear Estrogen receptors (ER) are cytoplasmic proteins; translocated to the nucleus to induce transcriptional signals after getting bound to the estrogen hormone. ER activation implicated in cancer cell proliferation of female reproductive organs. Thus, the discovery of ER antagonists is a reliable strategy to combat estrogen-dependent breast can...

Introduction: Estrogen receptor-related orphan receptors ERRα and ERRγ are essential regulators for cardiac metabolism. Mice lacking ERRα and ERRγ develops lethal cardiomyopathy and heart failure. Therefore, activation of ERR is a potential therapeutic intervention for HF treatment. However, no natural or synthetic ERR agonist is available to demon...

The estrogen related receptors (ERRs) are a subgroup of nuclear receptors that play a role in regulation of cellular metabolism. Prostate cancer (PCa) cells display altered metabolic signatures, such as the Warburg effect, and the ERRs have been implicated in driving this phenotype. Despite the lack of a known endogenous ligand, synthetic ligands t...

TLX is an orphan nuclear receptor that plays a critical role in both embryonic and adult neurogenesis, as well in the pathogenesis of glioblastomas. TLX functions predominately as a transcriptional repressor, but no natural ligands or high-affinity synthetic ligands have been identified. Here, we describe the identification of natural and synthetic...

Estrogen Related Receptors (ERRs) are key regulators of energy homeostasis and play important role in the etiology of metabolic disorders, skeletal muscle related disorders, and neurodegenerative diseases. Among the three ERR isoforms, ERRα emerged as a potential drug target for metabolic and neurodegenerative diseases. Although ERRβ/γ selective ag...

Numerous mutational studies have demonstrated that circadian clock proteins regulate behavior and metabolism. Nr1d1(Rev-erbα) is a key regulator of circadian gene expression and a pleiotropic regulator of skeletal muscle homeostasis and lipid metabolism. Loss of Rev-erbα expression induces muscular atrophy, high adiposity, and metabolic syndrome in...

Numerous mutational studies have demonstrated that circadian clock proteins regulate behavior and metabolism. Nr1d1(Rev-erb a ) is a key regulator of circadian gene expression and a pleiotropic regulator of skeletal muscle homeostasis and lipid metabolism. Loss of Rev-erb a expression induces muscular atrophy, high adiposity, and metabolic syndrome...

Many gut functions are attuned to circadian rhythm. Intestinal group 3 innate lymphoid cells (ILC3s) include NKp46 ⁺ and NKp46 ⁻ subsets, which are RORγt dependent and provide mucosal defense through secretion of interleukin-22 (IL-22) and IL-17. Because ILC3s highly express some key circadian clock genes, we investigated whether ILC3s are also att...

Hutchinson‐Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease. Mouse models have been instrumental for understanding HGPS mechanisms and for testing therapies, which to date have had only marginal benefits in mice and patients. Barriers to developing effective therapies include the unknown etiology of progeria mice early deat...

RAR-related orphan receptor g(RORg) is a nuclear receptor that plays an essential role in the development of T helper 17 (TH17) cells of the adaptive immune system. The NLRP3 inflammasome is a component of the innate immune system that processes interleukin (IL)-1β into a mature cytokine. Elevated activity of the NLRP3 inflammasome contributes to t...

Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrop...

Background & aims: The innate immune system responds not only to bacterial signals, but also to non-infectious danger-associated molecular patterns that activate the NLRP3 inflammasome complex after tissue injury. Immune functions vary over the course of the day, but it is not clear whether these changes affect the activity of the NLRP3 inflammaso...

Objective Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. Methods Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism wer...

The retinoic acid receptor-related receptor α (RORα) is a nuclear receptor that plays an important role in regulation of metabolism and the immune system. Genetic deletion of the receptor yields mice with significant cerebellar developmental issues associated with severe ataxia. Although many metabolic studies have been performed in these models, t...

Blood glucose and inflammatory parameters in male EIIARORα WT and EIIARORα KO mice under chow diet. (A) Fasted blood glucose level from males EIIARORα WT (white bar, n = 7) and EIIARORα KO (black bar, n = 7) after 10 weeks of high fat diet (HFD). (B) Blood IL-1b level in the males EIIARORα WT (white bar, n = 7) and EIIARORα KO (black bar, n = 7) af...

Food intake and activity of single-housed EIIARORα WT and EIIARORα KO mice. (A) Food intake of single-housed 12-week-old males EIIARORα WT (white bar, n = 8) and EIIARORα KO (black bar, n = 8) littermates under chow diet over a month. (B) Recording of single-housed 12-week-old males EIIARORα WT (white triangle, n = 8) and EIIARORα KO (black square,...

(A) Fasted blood glucose level from 13-month-old EIIARORα WT males (white bar, n = 6) and EIIARORα KO (black bar, n = 7) mice fed with normal chow diet. (B) Splenocytes from 15-month-old males EIIARORα WT (white bar, n = 6) and EIIARORα KO (black bar, n = 7) littermates were analyzed by flow cytometry for Th1 [CD3+CD4+IFNγ+ (left panel)], or regula...

Objective: Cardiovascular diseases (CVDs) are the leading cause of mortality in Western countries. Atherosclerosis is a multi-step inflammatory disease characterized at early stages by accumulation of cholesterol in the arterial wall followed by recruitment of immune cells. We sought to determine if pharmacological suppression of RORα/γ activity is...

Autism is a developmental disorder of the nervous system associated with impaired social communication and interactions as well excessive repetitive behaviors. There are no drug therapies that directly target the pathology of this disease. The retinioic acid receptor-related orphan receptor α (RORα) is a nuclear receptor that has been demonstrated...

Resistance to thyroid hormone (RTH) is a rare genetic disease caused by reduced tissue sensitivity to thyroid hormone. The hallmark of RTH is elevated serum levels of thyroid hormone with unsuppressed thyrotropin (TSH). However, the most common form of RTH results from minor defects in the ligand-binding domain or hinge domain of the TRβ gene, resu...

In the United States, approximately 16 million people suffer from coronary heart disease (CHD) and its various complications. Despite significant research effort and advances in the field of cardiovascular diseases, atherosclerosis remains the leading cause of mortality. Atherosclerosis is a multi-step inflammatory disease characterized at the earl...

Background: Development of atherosclerosis is a complex process that involves both hyperlipidemia and inflammation. Therapies that can target both metabolic and inflammatory aspect of this disease have significant potential in the treatment of cardiovascular diseases. The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in re...

Significance Several developmental and physiological processes require that cells display a controlled ability to migrate in an orientated manner. This capacity is also reacquired by certain cancer cells during their progression toward aggressiveness that allows them to establish distant metastases. The Rho GTPases are instrumental in the control o...

The development of new pH-sensitive fluorescent probes based on a push-pull architecture is presented with a 2- dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofurane as strong electron acceptor group. With a small structural change, it is possible to obtain a large range of phenolic pKa from 4.8 to 8.6 with some close to neutrality, underlinin...

Hypothyroidism is associated with an increased occurrence of atherosclerosis suggesting some protective role for thyroid hormones. Hypercholesterolemia is one of the major risk factor to develop this disease. Here we show that the well-known thyroid hormone cholesterol lowering effect was dependent on TRβ liver activity. But most importantly TRα wa...

A family of fluorescent push–pull pH-responsive probes based on 2-dicyanomethylidene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran as a strong electron acceptor group is described. Small structural variations allow obtaining pKa ranging from 4.8 to 8.6, underlining the role of the substituent in modulating the acidic properties. Remarkable changes in th...

Thyroid hormone (TR) and liver X (LXR) receptors are transcription factors involved in lipogenesis. Both receptors recognize the same consensus DNA-response element in vitro. It was previously shown that their signaling pathways interact in the control of cholesterol elimination in the liver. In the present study, carbohydrate-response element-bind...