Andrea PAVES

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3D tumour microenvironment for Disease Modelling
PhD – Interpolytechnic doctorate Fellow (Italy)

SUMMARY
Dr. Andrea PAVESI is a biomedical engineer and researcher with expertise in developing in vitro model of the tumor microenvironment for cancer research. He earned his MS in Biomedical Engineering from Politecnico di Milano in 2008. He then pursued his PhD in Biomedical and Biomechanical Engineering. Following his PhD, he moved to Singapore to work as a post-doc at The Singapore-MIT Alliance for Research and Technology (SMART). He later became a Research Scientist from 2014 to 2016 under Professor Kamm's group. In 2017, he joined IMCB as a Junior Investigator. He is a co-founding and Scientific advisory board member of AIM Biotech a Singapore-based start-up.
Dr. Pavesi is primarily focused on replicating human tumor microenvironment features in the lab to study the human immune system and develop treatments for cancer-related diseases using organ-on-a-chip models. Specifically, he specializes in evaluating and improving immune cell populations to boost their effectiveness against solid tumors. He holds multiple positions, including Principal Investigator at IMCB, CO-Principal Investigator at the Mechanobiology Institute and SMART CAMP. His work explores the intersection of engineering, biology, and medicine, to advance the understanding of cancer immunotherapies and develop innovative treatments.

AWARDS & GRANTS
  • IMCB Discovery Catalyst grant (2024) 
  • IEO Decentralised GAP (2023)
  • NRF Mid-Sized Grant MSG (2023)
  • NMRC Clinician Scientist (CS-IRG) (2023)
  • PREPARE grant (CS1-2022-007) (2023)
  • COVID-19 TOP-UP GRANT (COVID19TUG) (2021)
  • AMED Catalyst Award (2020)
  • Young Individual Research Grant (OF-YIRG 2019)
  • SMART CAMP “Critical Analysis for Manufacturing Personalized Medicine.” (2019)
  • NRF - CRP 17th call grant awarded (2017)
  • Nanyang Technological University (NTU) Grant: Academic research fund (acrf) tier 1 application for a seed grant in complexity (2013)

RESEARCH

3D tumour microenvironment for Disease Modelling
Dr. Pavesi's research group focuses on developing and utilizing microfluidic platforms for cancer research, creating multicellular models that mimic specific human tissues. These platforms allow for fine-tuning of parameters such as co-culture of multiple cell types, oxygen levels, cytokine administration, and physical parameters like ECM stiffness. The group's research focuses on creating 3D tumour microenvironments for disease modelling, immunotherapy, and cell therapy, as well as developing organ-on-a-chip systems, cancer in-vitro models, and drug screening platforms. The ultimate goal is to create efficient preclinical tools for personalized medicine, enabling the matching of optimal drugs and techniques to individual cancer patients during clinical trials.

PUBLICATIONS   
  • Unveiling the influence of tumor microenvironment and spatial heterogeneity on Temozolomide resistance in glioblastoma using an advanced human in vitro model of the blood-brain barrier and glioblastoma
    MSY Lam, JY Aw, D Tan, R Vijayakumar, HY G Lim, S Yada, QY Pang, N Barker, C Tang, BT Ang, R M. Sobota, A Pavesi (2023).
    Small. https://doi.org/10.1002/smll.202302280 (IF 15.15)

  • Characterization of 3D heterocellular spheroids of pancreatic ductal adenocarcinoma for the study of cell interactions in the tumor immune microenvironment
    Giustarini, G Teng, A Pavesi, G Adriani (2023).
    Frontiers in Oncology. Volume 13 – 2023. (IF 5.7)

  • G9a/GLP inhibition during ex vivo lymphocyte expansion increases in vivo cytotoxicity of engineered TCR-T cells against hepatocellular carcinoma
    M Lam, J R Calderon, J R Ow, AW Joey,  D Tan, E Ceccarello, T Tabaglio, Y T Lim, Loo Chien Wang, R Sobota, G Adriani, A Bertoletti, E Guccione, A Pavesi (2022). 
    Nature Communications. https://doi.org/10.1038/s41467-023-36160-5 (IF 17.69)

  • A 3d pancreatic tumor model to study t cell infiltration
    H Mollica, Yi JTeo, A S Min Tan, D Zhi Ming Tan, P Decuzzi, A Pavesi, G Adriani (2021). 
    Biomaterials Science 9 (22), 7420-7431. (IF 7.59)

  • In vitro 3D liver tumor microenvironment models for immune cell therapy optimisation
    M Lam, J A Reales-Calderon, J R Ow, G Adriani, A Pavesi (2021).
    APL bioengineering 5 (4), 041502 (IF 6.58)

  • Human MAIT cells endowed with HBV specificity are cytotoxic and migrate towards HBV-HCC while retaining antimicrobial functions
    K Healy*, A Pavesi*, T Parrot, M J Sobkowiak, S E Reinsbach, H Davanian, A T Tan, S Aleman, J K Sandberg, A Bertoletti, M Sällberg Chen (2021) 
    JHEP Reports 3 (4), 100318 (IF 8.3)

PATENTS
  • A device and method for vascularising a cell aggregate (US20240018483A1)
    There is provided a device for vascularising a cell aggregate, the device comprising: a matrix region configured to contain a gel-like matrix and cells that form a vasculature network within the matrix region. The matrix region having at least one opening for positioning the cell aggregate therein based on a desired three-dimensional spatial location; and one or more fluidic regions configured to contain a supporting fluid that is capable of supporting vascularisation of the cell aggregate, the one or more fluidic regions being in fluid communication with the matrix region, wherein a flow passage from the one or more fluidic regions to a gel-like matrix disposed in the matrix region is configured to allow three-dimensional vascularisation around the cell aggregate and perfusion of the vasculature once formed. There is also provided a chip comprising a plurality of the device as disclosed herein and a method for vascularising a cell aggregate.

  • A well insert and a device for 3d cell culture and in vitro tissue model (WO2022197254A1)
    Multi-well plate compatible device or insert for three-dimensional (3D) cell cultures, use and kit thereof are provided. The device includes outer and inner walls, the inner wall defining a volume and is located within the outer wall, forming a cavity therebetween. It also includes a base configured to position a cell culture sample below the volume within the inner wall and one or more partitions connected to the base, connecting the inner wall to the outer wall and segmenting the cavity into a plurality of voids. Openings in surfaces forming the voids allow fluid flow from a first void, below the volume within the inner wall to a second void, the fluid flow configured to interact with the cell culture sample when flowing through a sample region within the inner wall. The sample region has a depth defined by a height of the inner wall greater than a length defined by an inner distance across the volume within the inner wall.

  • Blood brain barrier model in a 3d co-culture microfluidic system interactions (WO2017035119A1)
    An efficient in-vitro Blood Brain Barrier (BBB) model consisting of the key cells of the BBB - namely, neurons, astrocytes and endothelial cells - is provided, which permits recapitulating the in-vivo BBB and shedding light on contributions from each individual cell type. A microfluidic system for modeling the blood brain barrier comprises an optically transparent substrate, the substrate comprising: (i) at least one fluid channel; (ii) a first gel channel comprising a first gel region; (iii) a second gel channel comprising a second gel region; and (iv) at least one row of posts.
  • Microfluidic platform for investigating cell-based interactions (WO2016076795A1)
    A microfluidic platform for investigating cell-based interactions in accordance with the invention, includes comprises a chip base made of a suitable plastics material with the appropriate optical properties. The chip base has a plurality of ports in fluid communication with a microfluidic channel for containing a culture medium in which cells are held. Preferably a gas permeable laminate is bonded to a bottom surface of the chip base. Each port has an internal inlet, connecting the port with the microfluidic channel, and a trough for containing a small reservoir of culture medium fluid adjacent to the inlet wherein, in use, culture medium can be aspirated from the microfluidic channel via the trough rather than directly via the internal inlet.
  • A method to produce a microfluidic device having vertical electrodes and a device obtained from it (WO2011121427A2)
    A method is described to produce a microfluidic device from a watertight structure. The method comprises a step of forming, inside such a watertight structure, a first fluidic microchannel network, that can be filled with one or more fluids, organic and inorganic, to be stimulated or controlled, and a second network of microchannels, that can be filled with an electrically conductive material that can act as impedance or conductor and interacts with such one or more fluids to be stimulated or controlled. Moreover, a microfluidic device is described, made with the aforementioned method.