The University of Texas MD Anderson Cancer Center
Department of Cancer Biology
My general goal is to study the role of chronic inflammation and adaptive immunity in the control of tumor development and the response of various cancers to therapy. Furthermore, my group is interested in developing effective immunotherapeutic combination strategies, especially for cancers in which immune checkpoint inhibitors have not yet demonstrated significant efficacy.
Cancer development and its response to therapy are strongly influenced by innate and adaptive immunity, which can either promote or attenuate tumorigenesis, and also have opposing effects on therapeutic outcomes. Chronic inflammation promotes tumor development, progression, metastatic dissemination, as well as treatment resistance. Accumulation of genetic alterations and loss of normal cellular regulatory processes are associated with cancer development and malignant progression while causing expression of tumor-specific and tumor-associated antigens (neoantigens) that activate anti-tumor immune responses. Although signals that trigger acute inflammatory reactions stimulate dendritic cell maturation and antigen presentation, chronic inflammation can be immunosuppressive. This antagonism between inflammation and immunity can affect the outcome of both cancer treatment and response to pathogens (e.g. virus or bacteria).
Our central focus is to explore how obesity, alcohol and aging affect the epithelial, mesenchymal and immune cell metabolic reprogramming, thereby determine the balance between ongoing damage and repair mechanism, and regulate cancer development, particularly in liver and gastrointestinal tract. We aim to understand the underlying mechanism of how these factors regulate tumor development by affecting the immune system and supporting the induction of immunosuppressive microenvironment (Tumor extrinsic mechanism TME). Moreover, we will study how these factors influence the tissue homeostasis and stem cells fate and further support immunoescape mechanism by regulating pathways like the MHC-I antigen processing and presenting machinery (AgPPM) in cancer/stem cells (Cancer cell intrinsic mechanism). We hope that this information can be used to prevent cancer and develop new therapeutic approaches (see scheme).
Specific aims and projects:
- Explore how aging and lifestyle choices (e.g. obesity, alcohol) affect the immune system and support liver cancer (hepatocellular carcinoma) development and progression.
- Study the regulation of gut-liver-brain axis by diet-induced dysbiosis.
- Investigate the role of the host metabolism, microbiome and TME in shaping the humoral and cellular immunity focusing on IgA+ plasma cell and follicular helper T cell development.
- Identify the role of B cells particularly IgA+ plasma cells in cancer and Alzheimer.
- Determine the mechanism which regulates MHC AgPPM in cancer cells.
- The role of metabolism in epigenetic regulation of Type II IFN signaling and MHC AgPPM.
Education & Training
PhD, Charité-Medical Faculty of Free University of Berlin, 2010