Shahrzad Shirazi Fard
My research set out to investigate consequences of intra tumour cellular heterogeneity for the progression into refractory disease, with the objective to target residual disease and prevent metastasis
I obtained my PhD in 2014 from Uppsala University in developmental neuroscience. In my PhD-thesis I demonstrated that subpopulations of neuronal progenitor cells have innate properties that make them sensitive to tumor development. This illustrates the importance of understanding the heterogenic properties of developing tissues and relation to neoplastic formation. Following my PhD, I started a dual Post doc training in the group of prof. Lars Ährlund-Richter at Karolinska Institutet and in the group of Dr. Jan Mulder at SciLifeLab Karolinska Institutet. The research focused on a novel transplantation model for studying pediatric solid tumors together with a novel MULTIPLEX technique for enhanced correlation analysis of multiple cellular markers at the site of tumour metastasis. In September 2019 I obtained an Assistant Professorship at Karolinska Institutet.
Currently the mechanisms underlying therapy outcomes are largely unknown, but both genetic and non-genetic components have been implicated. Data from us and others have indicated that distinct protective cell cycle-phases may play a significant role for chemotherapy-resistance, with poorly understood mechanisms. Furthermore, the microenvironment has been suggested to influence the cell cycle profile. This is of outmost importance since most tumours respond to first-line therapy and can even be brought to complete clinical remission, but local and systemic relapse remain a major therapeutic challenge, urging the need for novel in vivo models representing homologous (i.e. human-human) signalling, when investigating therapy resistance and regrowth. For this a novel transplantation model for studying pediatric solid tumors is used. The model differs from existing ones in that it includes a human environment for tumor growth. The approach has been shown to be especially applicable for tumors originating early in life, allowing precise and more clinically relevant mapping of the events of clonal selection leading to therapy-resistance and relapse.
Original papers - selected
Ödborn Jönsson L, Sahi M, Lopez-Lorenzo X, KellerF.L, Kostopoulou O.N, Herold N, Ährlund-Richter L, Shirazi Fard S# “Heterogeneities in cell cycle checkpoint activation following doxorubicin treatment reveal targetable vulnerabilities in TP53 mutated ultra high-risk neuroblastoma cell lines”. Int. J. Mol. Sci. 2021, 22(7), 3664. # corresponding author
Hultman I, Haeggblom L, Rognmo I, Jansson Edqivst J, Blomberg E, Ali R, Phillips L, Sandstedt B, Kogner P, Shirazi Fard S*, Ährlund-Richter L*. Doxorubicin-provoked increase of mitotic activity and concomitant drain of G0-pool in therapy-resistant BE(2)-C neuroblastoma. PLoS One. 2018 Jan 17;13(1):e0190970. * equal contribution.
Shirazi Fard S*, Blixt MKE,* Hallböök F. “The p53 co-activator Zac1 neither induces cell cycle arrest nor apoptosis in chicken Lim1 horizontal progenitor cells.” Cell Death Dis. 2015 Sep 07 * equal contribution
Shirazi Fard S, Thyselius M, All-Ericsson C, Hallböök F. "The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.” Cell Cycle. 2014;13(23):3698-706. # Editorial comment in: Cell Cycle 2015;14(8):1136-7.
Shirazi Fard S, All-Ericsson C, Hallböök F.” The heterogenic final cell cycle of chicken retinal Lim1 horizontal cells is not regulated by the DNA damage response pathway.” Cell Cycle. 2014 Feb 1;13(3):408-17.
Shirazi Fard S, Jarrin M, Boije H, Fillon V, All-Eriksson and Hallböök F. “Heterogenic final cell cycle by chicken retinal Lim1 horizontal progenitor cells leads to heteroploid cells with a remaining replicated genome.” PLoS One. 2013;8(3):e59133.
- Current teaching
2021 KI PhD course - Translational Paediatric Oncology in the Era of Immunotherapy and Omics
2020 KI Biomedicine - Molecular Medicine & Oncology
2019- KI Medicine program – DFM 1 course, course module Development – from egg to embryo
- Main Supervisor
2021 Master thesis, Agnes Sorteberg, MSc, KTH
2021 Master thesis, Vesa Halipi, MSc, LTH
2020 Master thesis, Maryam Sahi, MSc, KTH
2020 Master thesis, Ximena Lopez Lorenzo, MSc, KTH
2019 Master thesis, Linnéa Ödborn Jönsson MSc, KTH
2018 Master thesis, Faye Keller MSc, Uppsala University
2009-2015 >350 hours of teaching, including lectures, seminars, and laboratory, for students of biomedical and medical education at Uppsala University.
2009-2014 Co-Supervision of 6 master students during their thesis.