Prof. Dr. Hardtke-Wolenski working group
The Hardtke-Wolenski working group investigates autoimmunity and immune tolerance in liver and intestinal diseases, with a particular focus on autoimmune hepatitis (AIH).
Based on chronic inflammation and metabolic dysregulation, we investigate mechanisms of tumorigenesis as well as the response to modern immunotherapies including immune checkpoint inhibitors and their immune-mediated side effects. The aim of our work is to develop precise, antigen-specific immunotherapies that specifically modulate pathological immune responses and enable translational application.
Autoimmunity and chronic inflammation of the liver and intestine are at the center of our research, with a particular focus on AIH. In addition, we investigate inflammatory bowel diseases, in particular ulcerative colitis and related forms, as model systems of persistent immune activation and impaired barrier function. Another focus is on metabolic inflammation (MASLD/MASH) as a clinically highly relevant interface between metabolic inflammation and organ damage. These chronic inflammatory states promote the development of tumors, in particular hepatocellular carcinoma (HCC), and at the same time influence the course and treatability of immune-mediated diseases.
We investigate the mechanisms that mediate between protective immune response and pathological autoimmunity. The focus is on regulatory T cells (Tregs) as the central control center of immune tolerance in the liver and intestine. We analyze how function, stability and antigen specificity of Tregs are altered in autoimmunity, chronic inflammation and tumor development. We also consider the gut-liver axis and the interaction between metabolic signals, microenvironment and immune response.
Modern immunotherapies, especially immune checkpoint inhibitors (ICI), open up new treatment options, but are often associated with immune-related adverse events (irAEs). We are investigating determinants of treatment response and mechanisms of irAEs, with a focus on manifestations in the liver and intestine. A key issue is how pre-existing autoimmunity (e.g. AIH) and MASLD/MASH influence efficacy and toxicity. The aim is to identify immunological markers and mechanisms that enable more precise risk and therapy stratification.
Our goal is antigen-specific and precise immunomodulation that specifically controls pathogenic immune reactions without unnecessarily weakening protective immunity. To this end, we are developing cellular strategies based on CAR technologies, in particular CAR-Tregs, to harness immune tolerance for therapeutic purposes. These approaches are relevant for applications in autoimmunity, in the control of therapy-associated autoimmunity (irAEs) and in transplantation medicine. The work has a translational focus and is being driven forward in close cooperation with model systems and patient-related issues.
Further information
Publications
You can find the current status of our scientific publications at PubMed.
- Publications of the AG Hardtke-Wolenski in PubMed
Patents
The Hardtke-Wolenski research group is involved in several patent-relevant developments in the field of antigen-specific immunomodulation. The focus is on CAR- and CAR-Treg-based strategies for autoimmunity and transplantation medicine.
1. liver-specific CAR for the induction of immune tolerance (transplantation, autoimmune hepatitis and inflammatory liver diseases)
EP000004442322A1; WO002024208756A1
2. ENTPD3-directed CAR / CAR-Tregs (type 1 diabetes / T1D; antigen-specific immunomodulation)
EP000004655325A1; WO002024156716A1
3. DGCR2-directed CAR / CAR-Tregs (type 1 diabetes / T1D; antigen-specific immunomodulation)
EP000004669343A1; WO002024175805A1
4. GLP-1R-directed CAR / CAR-Tregs (type 1 diabetes / T1D; antigen-specific immunomodulation)
EP000004683660A1; WO002024194355A1
5. CAR for the treatment of multiple sclerosis or Alzheimer's disease
EP000004512415A1; WO002025040799A1
6. CAR/CAR-Treg strategies for the treatment of inflammatory bowel disease
EP000004678187A1; WO002026012912A1
Working group
Prof. Dr. Matthias Hardtke-Wolenski
wolenski.matthias@mh-hannover.de
Hannover Medical School
Clinical Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology
OE 6815
Building J11, Level 1, Room 1390
Carl-Neuberg-Str. 1
30625 Hannover
Phone +49 511 532-9513
- Dr. Ana-Clara Davalos-Misslitz
- Ziting Zhao (PhD student)
- Ze-xuan Shi (MD student)
- Konstantinos Iordanidis (BTA)
We are pleased to announce that the following individuals have successfully completed their doctorates and have been honored for their outstanding achievements:
- Dr. Janine Dywicki (summa cum laude)
- Dr. Tom Pieper (summa cum laude)
- Dr. Michel Tenspolde (Award for best Master's thesis and summa cum laude)
- Dr. Katharina Zimmermann (summa cum laude)
We would like to thank the following people for their contribution to the success of this working group:
- Dr. Sandra Bufe
- Dr. Katja Fischer
- Dr. Celina Maria Hendriks
- Dr. Ümran Karsli-Ünal
- Dr. Valerie Sätzler
- Dr. Nadja Seltrecht
- Akram Althanoon (MSc)
- Maike Stahlhut (Dipl. Biol.)
- Maike Hagedorn (MTA)
- Martin Hapke (BTA)
- Maren Lieber (MTA)
- Artur Wilms (BTA)