Bio


I received my PharmD from the University of Strasbourg (France) in 2018. I completed my PhD in Oncology and Cell Biology in 2020 in Dr. Catherine Tomasetto's group in IGBMC (France) studying cell metabolism and cell signaling in breast cancer. I am now a postdoctal fellow in Dr. Katrin Svensson lab and I am highly interested in understanding the molecular mechanisms of non-classical hormones in metabolic diseases.

Honors & Awards


  • Dean's fellowship, School of Medicine, Stanford (2022)
  • Ph.D research grant, allocated by the French Government after competitive exam, Doctoral School of Strasbourg (2016-2019)

Boards, Advisory Committees, Professional Organizations


  • member, American Heart Association (AHA) (2021 - 2022)
  • member, Stanford Cardiovascular Institute CVI (2022 - Present)
  • member, Stanford Diabetes Research Center (2021 - Present)
  • member, Maternal & Child Health Research Institute (MCHRI) (2021 - Present)

Professional Education


  • Doctor of Philosophy, Universite De Strasbourg (2020)
  • Doctor of Pharmacy, Universite De Strasbourg (2018)
  • Master of Science, Universite De Strasbourg (2016)
  • PhD, Doctoral School of Strasbourg, France, Molecular and cellular biology, lipid metabolism, cancer biology (2020)
  • PharmD, University of Strasbourg, France, Pharmacy (2018)

Stanford Advisors


Patents


  • Katrin J. Svensson, Laetitia Voilquin. "United States Patent 63/226,600 Therapeutic Uses of Isthmin Protein", Leland Stanford Junior University, Jul 28, 2022

Lab Affiliations


All Publications


  • Phosphoproteomic mapping reveals distinct signaling actions and activation of protein synthesis and muscle hypertrophy by Isthmin-1 Zhao, M., Banhos Dannieskiold-Samsøe, N., Ulicna, L., Nguyen, Q., Voilquin, L., Lee, D., White, J., Jiang, Z., Cuthbert, N., Paramasivam, S., Bielczyk-Maczynska, E., Van Rechem, C., Svensson, K. bioRxiv. 2022
  • Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Cell metabolism Jiang, Z., Zhao, M., Voilquin, L., Jung, Y., Aikio, M. A., Sahai, T., Dou, F. Y., Roche, A. M., Carcamo-Orive, I., Knowles, J. W., Wabitsch, M., Appel, E. A., Maikawa, C. L., Camporez, J. P., Shulman, G. I., Tsai, L., Rosen, E. D., Gardner, C. D., Spiegelman, B. M., Svensson, K. J. 2021

    Abstract

    With the increasing prevalence of type 2 diabetes and fatty liver disease, there is still an unmet need to better treat hyperglycemia and hyperlipidemia. Here, we identify isthmin-1 (Ism1) as an adipokine and one that has a dual role in increasing adipose glucose uptake while suppressing hepatic lipid synthesis. Ism1 ablation results in impaired glucose tolerance, reduced adipose glucose uptake, and reduced insulin sensitivity, demonstrating an endogenous function for Ism1 in glucose regulation. Mechanistically, Ism1 activates a PI3K-AKT signaling pathway independently of the insulin and insulin-like growth factor receptors. Notably, while the glucoregulatory function is shared with insulin, Ism1 counteracts lipid accumulation in the liver by switching hepatocytes from a lipogenic to a protein synthesis state. Furthermore, therapeutic dosing of recombinant Ism1 improves diabetes in diet-induced obese mice and ameliorates hepatic steatosis in a diet-induced fatty liver mouse model. These findings uncover an unexpected, bioactive protein hormone that might have simultaneous therapeutic potential for diabetes and fatty liver disease.

    View details for DOI 10.1016/j.cmet.2021.07.010

    View details for PubMedID 34348115

  • FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts EMBO JOURNAL Di Mattia, T., Martinet, A., Ikhlef, S., McEwen, A. G., Nomine, Y., Wendling, C., Poussin-Courmontagne, P., Voilquin, L., Eberling, P., Ruffenach, F., Cavarelli, J., Slee, J., Levine, T. P., Drin, G., Tomasetto, C., Alpy, F. 2020; 39 (23): e104369

    Abstract

    Organelles are physically connected in membrane contact sites. The endoplasmic reticulum possesses three major receptors, VAP-A, VAP-B, and MOSPD2, which interact with proteins at the surface of other organelles to build contacts. VAP-A, VAP-B, and MOSPD2 contain an MSP domain, which binds a motif named FFAT (two phenylalanines in an acidic tract). In this study, we identified a non-conventional FFAT motif where a conserved acidic residue is replaced by a serine/threonine. We show that phosphorylation of this serine/threonine is critical for non-conventional FFAT motifs (named Phospho-FFAT) to be recognized by the MSP domain. Moreover, structural analyses of the MSP domain alone or in complex with conventional and Phospho-FFAT peptides revealed new mechanisms of interaction. Based on these new insights, we produced a novel prediction algorithm, which expands the repertoire of candidate proteins with a Phospho-FFAT that are able to create membrane contact sites. Using a prototypical tethering complex made by STARD3 and VAP, we showed that phosphorylation is instrumental for the formation of ER-endosome contacts, and their sterol transfer function. This study reveals that phosphorylation acts as a general switch for inter-organelle contacts.

    View details for DOI 10.15252/embj.2019104369

    View details for Web of Science ID 000585124000001

    View details for PubMedID 33124732

    View details for PubMedCentralID PMC7705450

  • Modular Conjugation of a Potent Anti-HER2 Immunotoxin Using Coassociating Peptides BIOCONJUGATE CHEMISTRY Stoessel, A., Groysbeck, N., Guyot, L., Barret, L., Nomine, Y., Nguekeu-Zebaze, L., Bender, A., Voilquin, L., Lutz, T., Pallaoro, N., Blocat, M., Deville, C., Masson, M., Zuber, G., Chatton, B., Donzeau, M. 2020; 31 (10): 2421-2430

    Abstract

    Immunotoxins are emerging candidates for cancer therapeutics. These biomolecules consist of a cell-targeting protein combined to a polypeptide toxin. Associations of both entities can be achieved either chemically by covalent bonds or genetically creating fusion proteins. However, chemical agents can affect the activity and/or stability of the conjugate proteins, and additional purification steps are often required to isolate the final conjugate from unwanted byproducts. As for fusion proteins, they often suffer from low solubility and yield. In this report, we describe a straightforward conjugation process to generate an immunotoxin using coassociating peptides (named K3 and E3), originating from the tetramerization domain of p53. To that end, a nanobody targeting the human epidermal growth factor receptor 2 (nano-HER2) and a protein toxin fragment from Pseudomonas aeruginosa exotoxin A (TOX) were genetically fused to the E3 and K3 peptides. Entities were produced separately in Escherichia coli in soluble forms and at high yields. The nano-HER2 fused to the E3 or K3 helixes (nano-HER2-E3 and nano-HER2-K3) and the coassembled immunotoxins (nano-HER2-K3E3-TOX and nano-HER2-E3K3-TOX) presented binding specificity on HER2-overexpressing cells with relative binding constants in the low nanomolar to picomolar range. Both toxin modules (E3-TOX and K3-TOX) and the combined immunotoxins exhibited similar cytotoxicity levels compared to the toxin alone (TOX). Finally, nano-HER2-K3E3-TOX and nano-HER2-E3K3-TOX evaluated on various breast cancer cells were highly potent and specific to killing HER2-overexpressing breast cancer cells with IC50 values in the picomolar range. Altogether, we demonstrate that this noncovalent conjugation method using two coassembling peptides can be easily implemented for the modular engineering of immunotoxins targeting different types of cancers.

    View details for DOI 10.1021/acs.bioconjchem.0c00482

    View details for Web of Science ID 000584490900017

    View details for PubMedID 32996763

  • Another hijack! Some enteroviruses co-opt the c10orf76/PI4KB complex for their own good. EMBO reports Voilquin, L., Di Mattia, T., Alpy, F. 2020; 21 (2): e49876

    Abstract

    Enteroviruses, members of the Picornaviridae family, are non-enveloped and single-stranded RNA viruses responsible for several human diseases. During infection, these viruses build membrane-bound organelles, called replication organelles (ROs), where new virions are assembled. ROs are highly enriched in phosphatidylinositol 4-phosphate (PI4P) produced by the host lipid kinase PI4KB. In this issue of EMBO Reports, McPhail et al [1] characterize a complex, formed by PI4KB and the c10orf76 protein, which is involved in PI4P production. They show that this machinery is hijacked by specific enteroviruses such as coxsackievirus A10 for their replication.

    View details for DOI 10.15252/embr.201949876

    View details for PubMedID 31919962

    View details for PubMedCentralID PMC7001151

  • STARD3: A Swiss Army Knife for Intracellular Cholesterol Transport STARD3: A Swiss Army Knife for Intracellular Cholesterol Transport Voilquin, L., Lodi, M., Di Mattia, T., Chenard, M., Mathelin, C., Alpy, F., Tomasetto, C. 2019
  • Intracellular and Plasma Membrane Cholesterol Labeling and Quantification Using Filipin and GFP-D4 INTRACELLULAR LIPID TRANSPORT: METHODS AND PROTOCOLS Wilhelm, L. P., Voilquin, L., Kobayashi, T., Tomasetto, C., Alpy, F., Drin, G. 2019; 1949: 137-152

    Abstract

    Cholesterol, a major component of biological membranes, is rapidly trafficked and unevenly distributed between organelles. Anomalies of intracellular cholesterol distribution are the hallmark of a number of lysosomal lipid storage disorders. A major methodological obstacle for studying cholesterol trafficking is tracing this molecule in situ. The use of fluorescent probes that specifically bind cholesterol allows the visualization and imaging of cellular cholesterol. Here, we describe a series of assays optimized for quantifying free cholesterol in cell populations and at the single cell level, both at the plasma membrane and inside cells. These methods use two fluorescent probes: the D4 fragment of perfringolysin O fused to GFP (GFP-D4) and the polyene macrolide filipin. First, we report a robust method for quantifying plasma membrane cholesterol by flow cytometry using the GFP-D4 probe. Second, to optically distinguish and quantify intracellular cholesterol accumulation, we have adapted the classical filipin cholesterol staining protocol. Indeed, we observed that treatment of living cells with methyl-β-cyclodextrin, a chemical known to extract cholesterol from the plasma membrane, improves the visualization of the intracellular cholesterol pool with filipin. To complement these staining procedures, we developed an image analysis protocol based on image segmentation to quantify, in a robust manner, intracellular cholesterol stained with filipin. Thus, this chapter is a guideline for cellular cholesterol staining and signal quantification.

    View details for DOI 10.1007/978-1-4939-9136-5_11

    View details for Web of Science ID 000608835800012

    View details for PubMedID 30790254