Project Title: Gene expression variation in primary melanoma in immunological pathways related to survival.
PhD awarded: March 2019
I have obtained a BSc degree in Molecular Biology, and an International Master degree in Medical Biotechnology, co-funded by the European Union within the European Social Fund, at the Adam Mickiewicz University (AMU) in Poznan, Poland.
I have been interested in cancer since I started my studies. Therefore, I took part in many activities to gather and share knowledge about cancer. I have taken part in conferences in Poland and abroad. I founded a Student Association Section of Molecular Cancer Research aiming at informing students and teenagers via organizing lectures/quizzes/laboratory performances in various science festivals.
There is not only science, which amazes me in this world. I love to explore nature gifts such as wind and snow by windsurfing and snowboarding. I enjoy spending time at the sea side and in the mountains with my friends and family, especially with my one-year-old son Hugo. Additionally, from time to time I try to play drums, which raises many protests from my family members.
I completed my PhD at the University of Leeds (UK) in the framework of a Marie Skłodowska-Curie Early Training Network (MELGEN). My PhD project focused on analyses of gene expression, DNA copy number, and clinical data from primary (very early stage) cutaneous melanoma samples from one of the largest primary melanoma cohorts – Leeds Melanoma Cohort (LMC) (Pozniak et al, 2019). The aim of my project was to improve our understanding of immune responses to primary, treatment naïve melanoma using various bioinformatic, statistical, and computational methods, and some laboratory techniques. Using gene expression data, I created immune cell scores and classified patients based on their expression intensity. I have identified three immune subgroups of the patients, which were associated with prognosis and various clinico-pathological factors. I have also interrogated these patients’ subgroups using environmental exposures, such as smoking and showed that immune responses within tumors are not protective for melanoma patients if one ever smoked cigarettes.
For my PhD project, I have been utilizing software packages such as STATA and R to perform statistical and bioinformatics analysis of gene expression, copy number and clinical data. I did not receive training in bioinformatics prior my PhD, hence I have been learning all the in-silico approaches during the PhD period. In order to learn more about data handling and processing, I undertook an internship with the Eagle Genomics company on the Welcome Trust Genome Campus, in Cambridge UK. During my doctoral studies, I have learnt the basics of high-performance computing and the Unix operating system. Additionally, to my main PhD goals I have also performed some gene wide association study (GWAS) analysis to find germline single nucleotide polymorphisms (SNPs) associated with immune cell score imputed using gene expression data from melanoma tumors.
Regarding laboratory work, I was involved in the project focusing on analysis of copy number data from formalin paraffin embedded (FFPE) melanoma samples, for which I have performed Multiplex Ligation-independent Probe Amplification (MLPA) and analyzed the results (Filia et al, 2019). Moreover, I performed immunohistochemical staining for several proteins of interest that have been chosen (based on gene expression data) as candidates associated with immune responses to melanoma. I also evaluated the staining intensity and location using light microscopy.
To meet the aims of my PhD project, I collaborated with scientists from the host institution as well as with researchers from the University of Zurich. Additionally, I collaborated with researchers from Indian Institute of Science in India, for whom I have used the LMC gene expression and survival data to validate the results obtained from their in-vitro experiments (Metri et al, 2017). I have also performed analyses of gene expression and copy number data of the LMC for Prof. David Fisher (Harvard Medical School, USA). This collaborative work is currently under revision in Cancer Discovery. Lastly, I have performed some statistical analysis using gene expression and single nucleotide pleomorphism data for a study with scientists from Oslo University Hospital in Norway, which was recently published in Pigment Cell & Melanoma Research (Juraleviciute et al, 2019).
Metri R, Mohan A, Nsengimana J, Pozniak J, Molina-Paris C, Newton-Bishop J, Bishop D, Chandra N. Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach. Sci Rep. 2017 Dec 11;7(1):17314. Available at: https://www.nature.com/articles/s41598-017-17330-0
Nsengimana J, Laye J, Filia A, O’Shea S, Muralidhar S, Poźniak J, Droop A, Chan M, Walker C, Parkinson L, Gascoyne J, Mell T, Polso M, Jewell R, Randerson-Moor J, Cook GP, Bishop DT, Newton-Bishop J. β-Catenin-mediated immune evasion pathway frequently operates in primary cutaneous melanomas. J Clin Invest. 2018 May 1;128(5):2048-2063. Available at: https://www.jci.org/articles/view/95351
Poźniak J, Nsengimana J, Laye JP, O’Shea SJ, Diaz JMS, Droop AP, Filia A, Harland M, Davies JR, Mell T, Randerson-Moor JA, Muralidhar S, Hogan SA, Freiberger SN, Levesque MP, Cook GP, Bishop DT, Newton-Bishop J. Genetic and Environmental Determinants of Immune Response to Cutaneous Melanoma. Cancer Res. 2019 May 15;79(10):2684-2696 Available at: https://cancerres.aacrjournals.org/content/79/10/2684
Filia A, Droop A, Harland M, Thygesen H, Randerson-Moor J, Snowden H, Taylor C, Diaz JMS, Pozniak J, Nsengimana J, Laye J, Newton-Bishop JA, Bishop DT. High-Resolution Copy Number Patterns From Clinically Relevant FFPE Material. Sci Rep. 2019 Jun 20;9(1):8908. Available at: https://www.nature.com/articles/s41598-019-45210-2
Juraleviciute M, Pozniak J, Nsengimana J, Harland M, Randerson-Moor J, Wernhoff P, Bassarova A, Øy G.F, Trøen G, Flørenes VA, Bishop DT, Herlyn M, Newton-Bishop J, Slipicevic A. MX 2 is a novel regulator of cell cycle in melanoma cells. Pigment Cell Melanoma Res. 2019; 00: 1– 12. Available at: https://onlinelibrary.wiley.com/doi/full/10.1111/pcmr.12837
Thakur R, Laye JP, Lauss M, Diaz JMS, O’Shea SJ, Poźniak J, Filia A, Harland M, Gascoyne J, Randerson-Moor JA, Chan M, Mell T, Jönsson G, Bishop DT, Newton-Bishop J, Barrett JH. Transcriptomic Analysis Reveals Prognostic Molecular Signatures of Stage I Melanoma. Clin Cancer Res. 2019 Dec 15;25(24):7424-7435. Available at: https://clincancerres.aacrjournals.org/content/25/24/7424