Forscherdatenbank

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Prof. Dr. Alexander Weber

Tübingen
University of Tübingen Interfaculty

Institute for Cell Biology Department of Immunology

Auf der Morgenstelle 15 Office 1.002

72076 Tübingen

Programme

Exploitation of Oncogenic Mechanisms (EOM)

Cancer Immunotherapy (CI)

Übersicht

Innate immunity employs so-called pattern recognition receptors (PRRs) to detect a variety of different microbes, including bacteria, viruses and fungi based on so-called microbe-associated molecular patterns (MAMPs), as well as endogenous danger signals (DAMPs). Upon engagement, PRRs initiate distinct intracellular signaling pathways via receptor-proximal adaptor molecules. These in turn regulate subsequent effector responses, e.g. transcription factor-mediated gene transcription or caspase-mediated cleavage events but also affect cellular maturation, differentiation or survival and subsequent adaptive immune responses. The effective activation of innate and subsequent adaptive antigen-focused immune responses by PRR is utilized in vaccination approaches in both cancer immunotherapy as well as anti-infectious strategies, where adjuvants containing MAMPs are used.

Our group works on the molecular, cellular and immunological levels of PRR signaling pathways. For example, on the molecular and cellular level the emphasis is on the determinants of ligand recognition (for naturally occurring MAMPs as well as adjuvants), signal transduction events (and their regulation), as well as the influence of genetic variants in PRR genes on these processes in relation to infection or cancer. We also seek to understand cellular and immunological contributions of PRR function in inflammation and different cancer entities, in particular colorectal cancer and B cell lymphoma. Our work includes biochemical assays, molecular and cellular model systems but also different human and murine primary cell populations and in vivo models.

Within DKTK specific contributions are mainly to the programs “Cancer Immunotherapy” (CI)  and “Exploitation of Oncogenic Mechanisms” (EOM) with the following specific questions:

  • PRR agonists as adjuvants for immunotherapy (CI)
  • Recurrent MYD88 mutations as tumor-specific epitopes in cancer immunotherapy of B cell malignancies (CI)
  • Oncogenic mechanism of MYD88 mutations in B cell malignancies (EOM)
  • PRR germline variants for risk stratification in colorectal cancer
  • PRR pathway regulation of intestinal inflammation in colorectal cancer (EOM)
  • Bruton’s tyrosine kinase signaling in malignancy and host response (CI, EOM)

Further information and recent publications see http://www.immunology-tuebingen.de/groups/alexander-nr-weber.html

DKTK Junior Group Leader for Cancer Systems Biology

Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance. 

Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.