Klughammer Lab - Research
Mohammad Mokhtari: Charting the immune system’s response to exercise at high molecular and cellular resolution using single cell transcriptomics
Physical stress during exercise is known to be a potent, physiological stimulator of the immune system, seemingly without imminent threat. Exercise-induced changes include shifts in cell type composition as well as molecular activation states of peripheral mononuclear cells (PBMCs), circulating in the blood stream.
This project aims to explore the cell-type resolved dynamics of exercise-induced alterations in the immune system on the level of cellular composition and transcriptional responses - specifically inflammatory and anti-inflammatory pathways - using single-cell RNA sequencing (scRNA-seq). We explore the kinetics of these changes through time-series data and transcriptome-wide trajectory inference, and we set them in context with pathological scenarios of immune system activation such as infections and auto-inflammatory diseases. Ultimately, by gaining insight into the molecular and evolutionary underpinnings of exercise-induced immune system activation and subsequent deactivation, we hope to further its potential as "adjuvant therapy" in clinical settings.
Robert Strasser: Chemotherapeutic impact on the immune microenvironment in metastatic breast cancer
In women, breast cancer is the most common type of cancer, having a global incidence of over two million in 2020. In a fifth of all breast cancer diagnoses, liver metastases occur, which, despite treatment with hormone- and/or chemotherapy, lead to a 5-year survival rate of only 27%. In collaboration with researcher at the Broad Institute we investigate the heterogenous cellular ecosystem of liver metastasis at the level of individual cells, using single-nucleus RNA sequencing (snRNA-seq), and additionally on a spatial level, using Multiplexed error-robust fluorescence in situ hybridization (MERFISH). We assess and compare molecular and compositional differences between metastasis of patients that have or have not been treated with chemotherapy to better understand how chemotherapy might impact the effectiveness of immunotherapy as a complementary line of therapy.
Maira Torres: The single-cell expression landscape of microglia and their surrounding tissues in health and disease
Microglial cells are considered the resident macrophages of the brain and it is well established that there are various microglial populations across different brain regions. Until recently, this heterogeneity has not been comprehensively documented on a single-cell level.
This project strives to develop a computational framework for the efficient integration and analysis of published scRNA-seq data with the specific aim of elucidating the molecular diversity of microglia across various physiologic and pathologic conditions, generating translational insights and creating a widely applicable methodology.
Jan Watter: Methods development for high-dimensional spatio-molecular data analysis
Single cell, spatial and omics methods provide high-dimensional molecular measurements of cellular ecosystems at unprecedented scale and resolution. A key challenge is the meaningful interpretation of these information-rich biological data, with the goal to improve our understanding of cellular communication, interaction, and collective behaviour on a molecular level.
This project builds on our python-based framework called TACCO (Transfer of Annotations to Cells and their COmbinations) to improve and extend its functionalities. Specifically, it tackles a particularly challenging problem which is to transfer information from the ever-increasing wealth of scRNAseq data to spatial proteomics data such as CODEX, overcoming technical as well as biological discrepancies between these different modalities.