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The Geiger lab

T cells are key players in the immune system with the ability to detect and eliminate infected cells and tumors. We study molecular regulations underlying T cell activation and anti-tumor activity. For this, we use a wide range of technologies including mass spectrometry-based proteomics, functional genomics, mouse models and microfluidics-based systems. Our projects aim to provide detailed insights into T cell functionality that can be translated into the clinic to improve anti-cancer immunotherapies.

 

Quantitative Molecular Analysis of the T cell Response

To explore molecular mechanisms underlying the T cell response, we use quantitative systems approaches including  mass spectrometry-based proteomics, RNA-Seq, ATAC-Seq as well as several targeted approaches.

Immune Response to Liver Cancer

We are interested in the immune response to liver cancer. T cells that infiltrate liver tumors are often exhausted and do not work properly. To potentially increase their functionality, we study the underlying regulations by systematically analyzing tumor-infiltrating T cells with high-resolution mass spectrometry and functional assays.

Rapid Identification of T cell Receptors that recognize Tumor Antigens

We develop workflows to efficiently isolate T cells that recognize liver tumor antigens. Tumor-reactive T cells can be grown to large numbers and used for adoptive T cell therapies, a highly personalized form of cancer therapy. In collaboration with the research group of Andrew deMello (ETH Zürich), we use droplet-based microfluidics systems to manipulate and analyze single T cells in a high-throughput format.

 
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People

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Roger Geiger, PhD

Principle Investigator

Roger obtained his PhD from the ETH Zürich under the supervision of Ari Helenius. He received postdoctoral training in immunology with Antonio Lanzavecchia and in proteomics with Matthias Mann. Since 2017 Roger is an independent group leader at the IRB.

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Fernando Canale, PhD 

Postdoctoral Researcher

Fernando obtained his PhD from the Universidad Nacional de Córdoba in Argentina where he worked on mechanisms contributing to T cell exhaustion in tumor-infiltrating CD8+ T cells. He joined the Geiger lab as a postdoctoral researcher in 2018.

Gaia Antonini

PhD Student

Gaia obtained her bachelor and master degrees from the University of Milan Bicocca. She was then a postgraduate fellow at Experimental Immunology Unit at San Raffaele Hospital, in Milano. 

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Matteo Pecoraro, PhD

Research Associate

Matteo obtained his PhD at the Universitat Autònoma de Barcelona. He then received postdoctoral training in the laboratory of Matthias Mann at the Max Planck Institute in Munich, Germany. He joined the Geiger lab in 2019 as a research specialist is mass-spectrometry based proteomics.

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Wenjie Jin

PhD Student

Wenjie obtained his bachelor degree from Peking University and his master degree in pathology from the Case Western Reserve University.

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Giada Zoppi

PhD Student

Giada obtained her bachelor degree at the University of Varese. She then did her masters in Biology at the Institute of Oncology Research (IOR) before joining the Geiger lab in 2018.

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Ian Vogel

PhD Student

Ian completed his bachelor and master degrees at McGill University in Montréal, Canada. He then worked as a research associate in the labs of Judy Sakanari and Alexander Marson at the University of California, San Francisco (UCSF) before joining the Geiger Lab in 2019 as a PhD student.

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Yun Ding, PhD

Postdoctoral Researcher, Visiting Scientist

Yun is a postdoctoral researcher in the Department of Chemistry and Applied Biosciences at ETH Zurich in the laboratory of Andrew deMello. He specializes in the development of droplet-based microfluidic systems for processing next generation high-throughput biological and chemical experimentations.

Microfluidics Devices

We use droplet-based microfluidics devices that are developped in the laboratory of Professor deMello.

 

Selected publications

For a full list of publications:

 

Dynamics in protein translation

sustaining T cell preparedness

in Nature Immunology, August 2020

In response to pathogenic threats, naive T cells rapidly transition from a quiescent to an activated state, yet the underlying mechanisms are incompletely understood. Using a pulsed SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein turnover in human naive and activated T cells. Our datasets uncovered that transcription factors maintaining T cell quiescence had constitutively high turnover, which facilitated their depletion following activation. Furthermore, naive T cells maintained a surprisingly large number of idling ribosomes as well as 242 repressed mRNA species and a reservoir of glycolytic enzymes. These components were rapidly engaged following stimulation, promoting an immediate translational and glycolytic switch to ramp up the T cell activation program. Our data elucidate new insights into how T cells maintain a prepared state to mount a rapid immune response, and provide a resource of protein turnover, absolute translation kinetics and protein synthesis rates in T cells (https://www.immunomics.ch).

in Cell, October 2016

Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses.

in Nature Immunology, May 2017

The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not yet been established. We applied high-resolution mass-spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of >10,000 proteins in total. Protein copy numbers revealed a specialization of immune cells for ligand and receptor expression, thereby connecting distinct immune functions. By integrating total and secreted proteomes, we discovered fundamental intercellular communication structures and previously unknown connections between cell types. Our publicly accessible (http://www.immprot.org/) proteomic resource provides a framework for the orchestration of cellular interplay and a reference for altered communication associated with pathology.

 

Collaborators

 

Surgeons

We collaborate with Prof. Ercolani from the University Hospital in Bologna, with PD Dr. Rahbari from the University Clinic in Mannheim and with Dr. Seifert and Prof. Chavakis from the University Hospital in Dresden.

Microfluidics

The microfluidics devices that we use in our project are developed in the research group of Prof. deMello at the ETH Zürich.

 

Meet the lab

The area

Available Positions

We welcome all applications from individuals who are passionate about applying new technologies to studying the immune response to tumors. Please contact Roger with your CV and a cover letter.

Funding
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