Cancer Development and innate immune evasion
Tumor cells in order to thrive employ mechanisms that circumvent the immune response. This dynamic process is explained by the concept of cancer immunoediting, where some tumor cells variants have the capacity to escape the innate and adaptive immune system recognition, to then expand and hijack the host. However some tumor variants may protect less fit clones enabling immune evasion to then contribute to the whole tumor fitness, generating heterogeneous tumors with clones with different tumor traits. By combining live imaging, genetic and chemical tools we are studying the process of innate immune evasion and intra-tumoral clonal interactions using the zebrafish-larvae xenograft model. Understanding the process of innate immune rejection/ evasion may lead to new avenues of anti-cancer therapies based on modulating conserved innate immune mechanisms.

Zebrafish Avatars, towards personalised medicine
Despite advances in targeted cancer treatments, we still lack methods to predict how a specific cancer in a specific patient will respond to a given therapy. Consequently, patients go through rounds-of-trial-and-error approaches based on guidelines to find the best treatment, often subjected to unnecessary toxicity. We are developing zebrafish Patient Derived Xenografts (PDX) or “Avatars”, as sensors for cancer behavior and personalized therapy screening (Fior et al, PNAS 2017).
In collaboration with Miguel Godinho Ferreira, IRCAN – Nice, the Champalimaud Clinical Centre and the Hospital Amadora Sintra, we are testing the predictiveness of this assay in CRC and Breast Cancer, by comparing the therapeutic response obtained in patients with their matching zebrafish Avatars.
Please check Fior’s Lab page:
https://sites.google.com/neuro.fchampalimaud.org/rita-fior-lab

Rita Fior, PhD
Research Associate
rita.fior@neuro.fchampalimaud.org

Biography

Ana Logrado

ana.logrado@neuro.fchampalimaud.org

Cátia Almeida
Research Technician
catia.almeida@research.fchampalimaud.org

Marta Estrada, PhD
Postdoctoral Researcher
marta.estrada@research.fchampalimaud.org

Mayra Martinez
External PhD Student
mayra.martinez@research.fchampalimaud.org

PhD Student

Vanda Póvoa
PhD Student
vanda.povoa@neuro.fchampalimaud.org

Fior R* and Ferreira MG* (2018) Reply to Katsu and Baker: Using zebrafish PDX to screen drug sensitivity of endocrine-dependent cancers. Proc Natl Acad Sci U S A (doi:doi:10.1073/pnas.1802639115)

1. 2018 Fernandes S.F., Fior R., Pinto F., Gama-Carvalho M. and Saúde L. Fine-tuning of fgf8a expression through alternative polyadenylation has a selective impact on Fgf-associated developmental processes. BBA Gene Regulatory Mechanisms. Biochim Biophys (2018) Fine-tuning of fgf8a expression through alternative polyadenylation has a selective impact on Fgf-associated developmental processes. BBA Gene Regulatory Mechanisms. (doi: doi: 10.1016/j.bbagrm.2018.07.012. )

Fior R, Póvoa V, Mendes RV, Carvalho T, Gomes A, Figueiredo N, Ferreira MG. (2017) Single-cell functional and chemosensitive profiling of combinatorial colorectal therapy in zebrafish xenografts Proc Natl Acad Sci U S A PNAS 2017 September, 114 (39) , E8234-E8243 (doi: doi:10.1073/pnas.1618389114)

Lopes SS, Distel M, Linker C, Fior R, Monteiro R, Bianco IH, Portugues R, Strähle U, Saúde L. (2016) Report of the 4th European Zebrafish Principal Investigator Meeting. Zebrafish 2016 Dec;13 (6), 590-595 (doi:10.1089/zeb.2016.1364)

Fior R, Maxwell AA, Ma TP, Vezzaro A, Moens CB, Amacher SL, Lewis J, Saúde L. (2012) The differentiation and movement of presomitic mesoderm progenitor cells are controlled by Mesogenin 1 Development Dec;139(24): (139(24)), 4656-65 (doi:10.1242/dev.078923)

Cutty SJ, Fior R, Henriques PM, Saúde L, Wardle FC. (2012) Identification and expression analysis of two novel members of the Mesp family in zebrafish Int. J. Dev. Biol. 2012;56(4):285-94 (2012;56(4)), 285-94 (doi:10.1387/ijdb.113447sc.)

Fior R, Vilas-Boas F, Swedlow JR, Storey KG, Henrique D. (2011) A novel reporter of notch signalling indicates regulated and random Notch activation during vertebrate neurogenesis BMC Biol. Aug 31;9:58 (Aug 31;9:58), 9:58 (doi:10.1186/1741-7007-9-58)

Fior R, Henrique D. (2009) "Notch-Off": a perspective on the termination of Notch signalling. Int. J. Dev. Biol. 2009;53(8-10): (1379-84), 1379-84 (doi:10.1387/ijdb.072309rf)

Fior R, Henrique D. (2005) A novel hes5/hes6 circuitry of negative regulation controls Notch activity during neurogenesis. Dev. Biol. 2005 May 15;281(2):318-33. (281(2):318-33.), 318-33. (doi:10.1016/j.ydbio.2005.03.017)