Postdoctoral Fellow

Nataliia Pavliuchenko

Profile

I completed my PhD studies in Prague, Czech Republic, where my project focused on autoinflammatory osteomyelitis. My research investigated the role of binding partners of the adaptor protein PSTPIP2 in the development of osteomyelitis in vitro. After defending my PhD thesis in October 2023, I worked on a project exploring the molecular mechanisms behind the autoinflammatory disease Chronic Recurrent Multifocal Osteomyelitis (CRMO) in humans.

Currently, I am conducting research at the Josep Carreras Leukaemia Research Institute (IJC) in Barcelona, Spain. My work focuses on tumor-stroma crosstalk, specifically investigating how manipulation of the tumor microenvironment can hinder the proliferation and survival of malignant B cells in diffuse large B-cell lymphoma.

Project description

The tumor microenvironment (TME) mediates immunosuppressive state beneficial for malignant cells to escape immunity and this process mediated by rewiring of dendritic cells, natural killer, macrophages as well as fibroblasts. Over the years, gaining the knowledge on malignant cell biology and TME crosstalk led to development of novel therapies and proportional increase in the survival rate of the patients. The advent of single-cell RNA sequencing (scRNAseq) has provided in- depth look into gene expression of malignant cells while such data is still not sufficiently available for the cells of TME. In our project we aim to identify crucial gene signatures of dendritic cells, fibroblasts, macrophages, neutrophils, and T cells within the development of human diffuse large B-cell
lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma. High demand on B-cells for the production of high-affinity antibodies and the class-switch induces DNA repair pathways increasing the oncogenic mutation probability and chromosomal translocations that are quite common for B-cell lymphomas. In this process T cells and/or dendritic cells provide a signal for co- stimulatory B-cell-surface receptors required for a successful diversification of immunoglobulins.
We will incubate various cell types, including dendritic cells, fibroblasts, macrophages, neutrophils, and T cells with DLBCL cell lines available in the host lab and subject these cells to scRNAseq to identify genes that are upregulated upon engagement with malignant B-cells and benefit to proliferation of latter. We will further identify pathways of interest by associating an exploratory data analysis
(EDA) approach to gene set enrichment analysis (GSEA), and based on obtained gene sets and target key mediators, available inhibitors will be tested in different settings to further determine the effect on proliferation and survival of malignant B-cells. Finally, to translate these results into a new, safe and specific therapeutic options, we will validate in vitro data in a collection of DLBCL patient-derived xenograft (PDX) models.