Heiner Schäfer

Consolidated Researcher Details:

Institute:
Department of Internal Medicine I, University Kiel
Research Area:
Gastroenterology, Oncology
Prof. Dr. rer. nat.
Heiner Schäfer
hschaef [at] 1med.uni-kiel.de
+49 (0) 431 / 500 - 22 411
Researcher ID: C-1055-2011

Why this profession?

As a Biologist by training I started my research activity in the late 1980’s by studying the impact of regulatory peptides on cell growth and survival. During this work I got insight into complex diseases amongst which cancer is undoubtedly one of the most insidious and life-threatening pathological conditions. My research focus over the years is on stress pathways in epithelial cells that govern cellular adaptation processes and allow cells to cope with environmental hazards. If losing control these pathways favour carcinogenesis, thus targeting them would be a valuable tool for fighting against cancer. To achieve this goal, current work addresses different aspects of cellular stress responses and their mediators such as Nuclear Factor-kB (NF-kB) or Nuclear factor E2 related factor-2 (Nrf2). Both have an important role in many types of cancer including those of the gastrointestinal system (e.g. colorectal cancer or pancreatic cancer) and are supposed to be an integral part of tumor initiating pathways.

 

Why RTG Genes, Environment and Inflammation?

The transcription factor Nrf2 has a key role in the oxidative stress response and mediates profound cy­toprotection. Contrary to the previous view, it was recognized recently that deregulated Nrf2 activity contributes to car­cinogenesis. Deregulated Nrf2 activity can result from persistent oxidative stress, which is often seen in the permanent presence of inflammatory cells such as macro­phages during the course of a chronic inflammation, e.g. inflammatory bowel disease (IBD), or in the context of colorectal cancer (CRC). Under such conditions, epithelial cells adapt to oxidative stress through an en­hanced and durable activation of Nrf2. One conse­quence is an increased resistance to apoptosis, manifesting in chemo­resistance, but several other growth advantages are conferred by an enhanced Nrf2 activation, too. Recent data indicate that Nrf2 is involved in metabolic reprogramming, as well. In fact, the altered condition not only covers the high energy demand, but also ensures masses of glucose as intermediate metabolite for biomass production along with cell proliferation and tumor growth. Recently, it was shown that oxidative stress modulates the expression of key enzymes of glucose and energy metabolism as well as monocarboxylate transporters (MCT) - these are involved in the cellular balance of lactate -, thus pointing to a possible contribution of Nrf2 in cancer metabolism. This would particularly apply to inflammation associated cancers (IAC) initiated and promoted by persistent oxidative stress and Nrf2 dependent adaptation processes.