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.
Our research aims to decipher the complicated spatial interplay between tumour cells and the tumour microenvironment using MULTIPLEX genomic, transcriptomic and proteomic profiles in order to investigate consequences of tumour heterogeneity for the progression into refractory disease. Neuroblastoma is the most common extra cranial solid tumor in pediatrics and accounts for 15% of cancer related deaths in children. Even though the overall survival has increased following implementation of novel therapeutics; one third of high-risk patients will experience treatment failure. An outcome most likely influenced by the tumour microenvironment. Spatial multi-omics techniques enables better dissection of the tumour microenvironment through investigation of the spatial architecture. A combination of several novel multiparameter immunofluorescence analysis techniques is being used on patient biopsies. The single-cell approach allows us to investigate cell-cell interactions that might contributing to resistance. This is combined by targeted treatment in matched in vivo cell lines of neuroblastoma, in order to re-sensitize resistant tumour cells to therapy. An enhanced understanding of the intra-tumour heterogeneity and asynchronous therapy responsiveness are among the most important areas in tumour research and our work is anticipated to produce novel biological discoveries and encourage further development of therapies.
Original papers - selected
Sorteberg AL, Halipi V, Wickström M, Shirazi Fard S#, "The cyclin dependent kinase inhibitor p21Cip1/Waf1 is a therapeutic target in high-risk neuroblastoma". Front. Oncol. 2022 Sep 6; 12:906194. # corresponding author
Verhoeven BM, Mei S, Olsen TK, Gustafsson K, Valind A, Lindström A, Gisselsson D, Shirazi Fard S, Hagerling C, Kharchenko PV, Kogner P, Johnsen JI, Baryawno N. “The immune cell atlas of human neuroblastoma”. Cell Rep Med. 2022 Jun 8;100657.
Ödborn Jönsson L, Sahi M, Lopez-Lorenzo X, Keller F.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. # corresponding author
- Current teaching
2022 (Course Leader) KI PhD course - Translational Paediatric Oncology in the Era of Immunotherapy and Omics
2021 KI PhD course - Translational Paediatric Oncology in the Era of Immunotherapy and Omics
2020-2021 KI Biomedicine - Molecular Medicine & Oncology
2019-2020 KI Medicine program – DFM 1 course, course module Development – from egg to embryo
2021 - ongoing (Co-supervisor) Ioanna Tsea PhD-student
2022 Master thesis, Maja Lundström, MSc, KTH
2021 Master thesis, Mani Devaraj, MSc, KI
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