Nicole Marquardt

I completed my PhD in 2011 in Hannover, Germany, and was recruited to the Department of Medicine Huddinge the same year. Since 2019, I have been a PI and team leader in the department, and my team is currently based at the Center for Hematology and Regenerative Medicine (HERM).

I have extensive expertise in NK cell research, both in blood and tissues, with a primary focus on human NK cells in homeostasis and disease.

While NK cells in peripheral blood are well-characterized, much less is known about their counterparts in tissues. Blood-derived NK cells are thought to play a key role in hematologic malignancies, whereas tissue-resident NK cells likely serve as a first line of defense in organs such as the lung - particularly during respiratory viral infections - or play a pivotal role in combating solid tumors. Identifying distinct NK cell subsets that home to and reside in human tissues provides new insights into disease development, progression, and potential therapeutic strategies in tissue-specific pathologies.

Our team primarily studies NK cells in the human lung (healthy, tumor-free, tumor, and respiratory viral infections) but also investigates NK cells in other tissues and their tissue-homing capacities from blood. Specifically, we explore NK cell function and regulation in different regions of the respiratory tract and solid tumors. Additionally, we aim to understand the responsiveness of tissue-resident NK cells to viral infections such as influenza A and SARS-CoV-2. Our ultimate goal is to translate this knowledge into the development and optimization of prevention and treatment strategies for patients with lung cancer or respiratory viral infections.

Severe respiratory diseases such as COVID-19 and influenza are often associated with lung tissue damage, partly due to an excessive immune response. While Natural Killer (NK) cells play a crucial role in antiviral defense, surprisingly little is known about their regulation in respiratory viral infections. The overall aim of this project is to identify regulatory mechanisms of human blood and lung NK cells that could be targeted to treat patients with severe acute respiratory viral infections—ultimately balancing immune pathology and immune protection.

Through ongoing collaborations, we have access to non-infected human lung tissue, lung tissue from COVID-19 patients, and peripheral blood from individuals infected with influenza or SARS-CoV-2. This project integrates unique human clinical material, in vitro infection models using highly relevant viruses, and cutting-edge technologies to investigate NK cell biology in the infected lung. Our goal is to define NK cell subsets in the lung and their trafficking patterns during viral infections, with the long-term vision of reducing disease severity, hospitalization, and mortality.

Lung cancer remains the leading cause of cancer-related mortality worldwide. NK cells are well known for their ability to target and lyse tumor cells and are already a promising tool in the treatment of hematologic malignancies. However, NK cell-based therapies for solid tumors, including lung cancer, are still in their early stages. Major challenges include inefficient NK cell trafficking to the tumor site, poor tumor infiltration, antigen escape mechanisms, and an immunosuppressive tumor microenvironment. While our previous studies have identified distinct NK cell subsets in the human lung, little is known about their regulation in lung tissue and tumors.

This project aims to map the NK cell landscape in different regions of the healthy human lung and lung tumors. Our goal is to identify and harness NK cell subsets with the highest potential for tumor infiltration and cytotoxicity to develop improved NK cell-based therapies for lung cancer.

In collaboration with physicians and scientists at Karolinska University Hospital (Huddinge/Solna), we collect healthy lung tissue from organ donors as well as tumor-free tissue and lung tumors from patients undergoing surgery for suspected lung cancer. Key areas of focus include NK cell lung-homing, tumor infiltration, tissue residency, and cytotoxic potential. This project relies on advanced technologies such as high-parameter flow and spectral cytometry, RNA sequencing, and live cell imaging.

By combining unique human clinical material with state-of-the-art technologies, we aim to identify and optimize NK cell-based strategies for lung cancer treatment, ultimately working toward reducing disease severity, hospitalization, and mortality.

Course director for doctoral course "Tissue-specific immunology" (3072, Aii, 1.5 HEC, organized every second year)

Feedback from course (2023):

"The presenters that had a story to tell backing it up with real life data, not only reviews."
"I appreciated that the course leaders were flexible and tried their best to make everyone happy and content"
"I liked the setup of the course, good speakers and interesting topics! Good amount of breaks and overall a nice flow throughout the course."

Current and past members of the team

Current members

Nicole Wild, MSc

Doctoral student

Since 04/2022

Elena Bonaiti, PhD

Postdoc

Since 01/2024

Past members

Julia Schaden, BSc

Master student

2023-2024

Fabian Zoppelt, BSc

Internship student

02-07/2024

Camille Guedé, BSc

Internship student

Oct 2023-June 2024

Demi Brownlie, PhD

Postdoc

Nov 2019-October 2023

Now Postdoc at the Beatson West of Scotland Cancer Centre, UK

Pablo Clavero

Internship student

Feb-June 2022

Giampiero Valenzano

Internship student

January-July 2021

Kathleen Schlüter, BSc

Internship student

04-06/2021

Andreas von Kries, BSc

Internship/Master student

01/2020 - 02/2021

Now PhD student in the group of Adelheid Cerwenka, Mannheim, Germany.

Marlena Scharenberg, BSc

Master student

01-10/2017