Health & Pharma PhD Graduates – Summer 2022

iBET’s Health and Pharma Division has four new PhD graduates this Summer: Joana Almeida (Stem Cell Bioengineering Lab), Ana Rita Mendes (Biosystems and Data Science Group and Advanced Cell Models Lab), Ana Filipa Louro (Stem Cell Bioengineering Lab) and Francisca Arez (Advanced Cell Models Lab).

iBET congratulates the new Doctors for this important step in their careers and acknowledges their valuable contributions to the research areas of cell-based therapies, data science and in vitro models of disease at iBET.

Find below a PhD portrait of each of our new graduates.

Joana Almeida

PhD in Biomedical Engineering, University of Zaragoza (14^th June 2022)

Host Laboratories: Organ Bioengineering and Regenerative Medicine Lab at IIS-Aragon (Zaragoza, Spain) and Stem Cell Bioengineering Lab at iBET

Thesis Title: Generation and large-scale expansion of highly functional hPSC-derived hepatocytes for cellular therapies and bioengineered livers: the unknown role of human microbiome

Highlights:

• Novel insights into the acquisition of hepatic function during the early postnatal period and its association with intestinal microbiome
• Comprehensive overview of the microbial secretome and its impact on liver function
• Encouraging observations on the effect of microbial secretome in hPSC-HLC maturation and function in vitro
• Development of an integrated bioprocess for the expansion and differentiation of hiPSC into HLC using a scalable stirred-tank bioreactor
• Better understanding of the engraftment ability of hPSC-HLC.

Publications:

Almeida J.I. et al Hallmarks of the human intestinal microbiome on liver maturation and function. Journal of Hepatology 2022. 76(3):694-725. https://doi.org/10.1016/j.jhep.2021.10.015

Isidro, I.A., Vicente, P., Pais, D. A. M., Almeida, J.I. et al. Online monitoring of hiPSC expansion and hepatic differentiation in 3D culture by dielectric spectroscopy. Biotechnology and Bioengineering 2021. 118(9):3610-3617. https://doi.org/10.1002/bit.27751

Brovold M., Almeida J.I., et al. Naturally derived Biomaterials for Tissue Engineering Applications. Adv Exp Med Biol 2018. 1077:421-449. doi: 10.1007/978-981-13-0947-2_23.

Morini S., et al. Liver Tissue Engineering in Bioreactors for Stem Cell Expansion and Differentiation by Joaquim M S Cabral and Cláudia Lobato da Silva. 2018. Publisher: Boca Raton - Taylor & Francis, 2019

New position: Post-doc at Icahn School of Medicine at Mount Sinai (New York, USA)

Ana Rita Mendes

PhD in Bioengineering - MIT-Portugal Program, ITQB-NOVA, NOVA University Lisbon, 4^th July 2022

Host Laboratories: Biosystems and Data Science Group and Advanced Cell Models Lab, iBET

Thesis Title: “Harnessing complex metabolic signatures to predict drug efficacy in Ovarian Cancer”

Highlights:

• Establishment of a reliable drug efficacy readout method for the assessment of complex culture systems, namely patient-derived cell models
• Implementation of untargeted, semi-targeted, and targeted metabolomics frameworks for the analysis of patient-derived samples
• Identification of putative metabolic biomarker panels that discriminate ex vivo high-responders and low-responders to the standard-of-care treatment
• Implementation of tools to isolate extracellular vesicles from ascitic fluids of ovarian cancer patients and characterize their metabolome.

Publications:

• Mendes & Cox et al (2021) Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models. Scientific Reports 11:18571. https://doi.org/10.1038/s41598-021-97894-0

New Position: Biotech Venture Developer at NLC - The European Healthtech Venture Builder

Ana Filipa Louro

PhD in Bioengineering - MIT-Portugal Program, ITQB-NOVA, NOVA University Lisbon, 5th July 2022

Host Laboratory: Stem Cell Bioengineering Lab, iBET

Thesis title: “Cell-based and cell-free strategies for cardiac repair”

Highlights:

• Reporting of a novel human ECM-based strategy to promote hiPSC-cardiomyocytes(CM) maturation and a resulting versatile, biologically relevant, cardiac microtissue model that can serve as a new tool for in vitro cardiac disease modeling;
• Identification of a promising cell biofactory for extracellular vesicles (EV) production (hiPSC), with insights into EV-mediated effects in target cells;
• Identification of a transcriptomic molecular signature for hiPSC-EV characterization that can be used as critical quality attributes (CQA) in routine EV production, scale-up/out processes, and dose determination for in vitro and in vivo assays;
• Development of a potential in situ sustained delivery strategy for hiPSC-EV, compatible with different biofabrication techniques (casting versus bioprinting) and application systems for epicardial delivery.

Publications:

• M. F. Tenreiro, A. F. Louro, et al. Next generation of heart regenerative therapies: progress and promise of cardiac tissue engineering. npj Regen. Med. 6 (2021). https://doi.org/10.1038/s41536-021-00140-4

• H. V. Almeida, M. F. Tenreiro, A. F. Louro, et al. Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation. ACS Appl. Bio Mater. 4, 1888–1899 (2021). https://doi.org/10.1021/acsabm.0c01490

• F. Louro, et al. Bioactivity and miRNome Profiling of Native Extracellular Vesicles in human induced Pluripotent Stem Cell-Cardiomyocyte differentiation. Adv. Sci., e2104296 (2022). https://doi.org/10.1002/advs.202104296

• F. Louro, et al. Expression of Extracellular Vesicle PIWI-interacting RNAs throughout hiPSC-cardiomyocyte differentiation. Front. Physiol. 13:926528 (2022). https://doi.org/10.3389/fphys.2022.926528

New position: Post-doctoral researcher at the Stem Cell Bioengineering Lab (iBET)

Francisca Arez

PhD in Bioengineering, ITQB-NOVA, NOVA University Lisbon, 28^th July 2022

Host Laboratory: Cell Bioprocesses Lab & Advanced Cell Models Lab, iBET

Thesis Title: “Advancing liver-stage malaria in vitro models for drug discovery”

Highlights:

• Development of a human 3D model recapitulative of the hepatic infection by malaria parasites
• Integration of a spheroid-based model in the clinical development of an anti-plasmodial drug candidate
• Development of a scalable 3D culture strategy for cryopreserved primary human hepatocytes

Publications:

• Khandelwal, A., Arez, F., et al. (2022). Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside. Malaria Journal, 21(1), 151. https://doi.org/10.1186/s12936-022-04171-0

• Fontinha D.*, Arez F.*, et al. (2021) Pre-erythrocytic Activity of M5717 in Monotherapy and Combination in Preclinical Plasmodium Infection Models. ACS Infectious Diseases. https://doi.org/10.1021/acsinfecdis.1c00640
• Arez F.*, Rebelo SP.*, Fontinha D.*, et al (2019) Flexible 3D Cell-Based Platforms for the Discovery and Profiling of Novel Drugs Targeting Plasmodium Hepatic Infection. ACS Infectious Diseases. https://doi.org/10.1021/acsinfecdis.9b00144

New position: Post-doctoral researcher at the Advanced Cell Models Lab, iBET