Bio


My global research goal lies in exploring multiple imaging modalities using novel molecular contrast agents to address current unmet clinical needs with a large emphasis on ultrasound and magnetic resonance imaging. Primarily focused on developing imaging agents for disease early detection (i.e., inflammation, breast and pancreatic cancers) and treatment response monitoring in pre-clinical studies, I also explore targeted theranostic agents.

Professional Education


  • Doctor of Philosophy, University of Bordeaux, Bordeaux, France (2019)
  • Master of Science, Claude Bernard University, Lyon, France (2015)
  • Bachelor of Science, Claude Bernard University, Lyon, France (2013)

Stanford Advisors


All Publications


  • Inhaled Gold Nano-Star Carriers for Targeted Delivery of Triple Suicide Gene Therapy and Therapeutic MicroRNAs to Lung Metastases: Development and Validation in a Small Animal Model ADVANCED THERAPEUTICS Liu, Y., Sukumar, U., Jugniot, N., Seetharam, S., Rengaramachandran, A., Sadeghipour, N., Mukherjee, P., Krishnan, A., Massoud, T. F., Paulmurugan, R. 2022
  • Biomimetic nanobubbles for triple-negative breast cancer targeted ultrasound molecular imaging. Journal of nanobiotechnology Jugniot, N., Massoud, T. F., Dahl, J. J., Paulmurugan, R. 2022; 20 (1): 267

    Abstract

    Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with poor prognosis. Although anatomical imaging figures prominently for breast lesion screening, TNBC is often misdiagnosed, thus hindering early medical care. Ultrasound (US) molecular imaging using nanobubbles (NBs) capable of targeting tumor cells holds great promise for improved diagnosis and therapy. However, the lack of conventional biomarkers in TNBC impairs the development of current targeted agents. Here, we exploited the homotypic recognition of cancer cells to synthesize the first NBs based on TNBC cancer cell membrane (i.e., NBCCM) as a targeted diagnostic agent. We developed a microfluidic technology to synthesize NBCCM based on the self-assembly property of cell membranes in aqueous solutions. In vitro, optimal NBCCM had a hydrodynamic diameter of 683±162nm, showed long-lasting US contrast enhancements and homotypic affinity. In vivo, we demonstrated that NBCCM showed increased extravasation and retention in a TNBC mouse model compared to non-targeted NBs by US molecular imaging. Peak intensities and areas under the curves from time-intensity plots showed a significantly enhanced signal from NBCCM compared to non-targeted NBs (2.1-fold, P=0.004, and, 3.6-fold, P=0.0009, respectively). Immunofluorescence analysis further validated the presence of NBCCM in the tumor microenvironment. Circumventing the challenge for universal cancer biomarker identification, our approach could enable TNBC targeting regardless of tumor tissue heterogeneity, thus improving diagnosis and potentially gene/drug targeted delivery. Ultimately, our approach could be used to image many cancer types using biomimetic NBs prepared from their respective cancer cell membranes.

    View details for DOI 10.1186/s12951-022-01484-9

    View details for PubMedID 35689262

  • Expression and purification of a native Thy1-single-chain variable fragment for use in molecular imaging. Scientific reports Jugniot, N., Bam, R., Paulmurugan, R. 2021; 11 (1): 23026

    Abstract

    Molecular imaging using singlechain variable fragments (scFv) of antibodies targeting cancer specific antigens have been considered a non-immunogenic approach for early diagnosis in the clinic. Usually, production of proteins is performed within Escherichia coli. Recombinant proteins are either expressed in E. coli cytoplasm as insoluble inclusion bodies, that often need cumbersome denaturation and refolding processes, or secreted toward the periplasm as soluble proteins that highly reduce the overall yield. However, production of active scFvs in their native form, without any heterologous fusion, is required for clinical applications. In this study, we expressed an anti-thymocyte differentiation antigen-scFv (Thy1-scFv) as a fusion protein with a N-terminal sequence including 3*hexa-histidines, as purification tags, together with a Trx-tag and a S-tag for enhanced-solubility. Our strategy allowed to recover ~ 35% of Thy1-scFv in the soluble cytoplasmic fraction. An enterokinase cleavage site in between Thy1-scFv and the upstream tags was used to regenerate the protein with 97.7±2.3% purity without any tags. Thy1-scFv showed functionality towards its target on flow cytometry assays. Finally, in vivo molecular imaging using Thy1-scFv conjugated to an ultrasound contrast agent (MBThy1-scFv) demonstrated signal enhancement on a transgenic pancreatic ductal adenocarcinoma (PDAC) mouse model (3.1±1.2 a.u.) compared to non-targeted control (0.4±0.4 a.u.) suggesting potential for PDAC early diagnosis. Overall, our strategy facilitates the expression and purification of Thy1-scFv while introducing its ability for diagnostic molecular imaging of pancreatic cancer. The presented methodology could be expanded to other important eukaryotic proteins for various applications, including but not limited to molecular imaging.

    View details for DOI 10.1038/s41598-021-02445-2

    View details for PubMedID 34845270

  • Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer. Bioengineering & translational medicine Jugniot, N., Bam, R., Meuillet, E. J., Unger, E. C., Paulmurugan, R. 2021; 6 (1): e10183

    Abstract

    Pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis due to silent onset, resistance to therapies, and rapid spreading. Most patients are ineligible for curable surgery as they present with advanced disease at the time of diagnosis. Present diagnostic methods relying on anatomical changes have various limitations including difficulty to discriminate between benign and malignant conditions, invasiveness, the ambiguity of imaging results, or the inability to detect molecular biomarkers of PDAC initiation and progression. Therefore, new imaging technologies with high sensitivity and specificity are critically needed for accurately detecting PDAC and noninvasively characterizing molecular features driving its pathogenesis. Contrast enhanced targeted ultrasound (CETUS) is an upcoming molecular imaging modality that specifically addresses these issues. Unlike anatomical imaging modalities such as CT and MRI, molecular imaging using CETUS is promising for early and accurate detection of PDAC. The use of molecularly targeted microbubbles that bind to neovascular targets can enhance the ultrasound signal specifically from malignant PDAC tissues. This review discusses the current state of diagnostic imaging modalities for pancreatic cancer and places a special focus on ultrasound targeted-microbubble technology together with its clinical translatability for PDAC detection.

    View details for DOI 10.1002/btm2.10183

    View details for PubMedID 33532585

    View details for PubMedCentralID PMC7823123

  • Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer BIOENGINEERING & TRANSLATIONAL MEDICINE Jugniot, N., Bam, R., Meuillet, E. J., Unger, E. C., Paulmurugan, R. 2020

    View details for DOI 10.1002/btm2.10183

    View details for Web of Science ID 000569340100001