1. Regulation of inflammatory processes.

Inflammation is a response of cell/organism to harmful stimuli: mechanical, physical and biological. It is initiated by proinflammatory cytokines such as IL-1 and tumour necrosis factor as well as by cytokines from IL-6 family. The cytokines released by activated macrophages, fibroblasts, keratinocytes and endothelial cells stimulate hepatocytes and other cells to synthesis of acute phase proteins that are responsible for restoration of homeostasis. Inflammatory processes lead on molecular level to activation of signaling pathways and transcription factors. The aim of our study is to clarify regulation of inflammation on molecular level, identification of new proteins that are involved in initiation, course and termination of this process and determination of function of these proteins with the use of functional genomics methods.

2. Role of MCPIP1 in UV-induced stress response.

Skin acts as an important physical, biochemical, andimmunological barrier against various insults and is composed of the upper epidermis and the lower dermis. Another important aspect of skin function is its ability to self-renew and maintain homeostasis, which is achieved by proliferation and differentiation of epidermal stem cell population that gives rise to keratinocytes. Keratinocytes, in the various degree of differentiation span from the proliferative basal layer to the terminally differentiated horny layer. They are responsible for cohesion, barrier functions, and immunological reactions. Ultraviolet (UV) radiation is one of the most common physical insults causing skin irritation. Prolonged skin exposure to UV light leads to DNA damage, cell death and inflammation. Since MCPIP1 is a negative regulator of inflammation we aim to elucidate its function in keratinocytes exposed to UVB light.

3. Role of MCPIP1 in adipogenesis and obesity.

The adipose tissue is the largest organ in humans, representing approximately 10–30% of body weight. The classically attributed function of the adipose tissue is energy storage in the form of triglycerides. However, it is now known that the adipose tissue has also an endocrine role and it releases hundreds of different active molecules (adipokines) with multiple activities. Adipokines provide an extensive network of communication both within the adipose tissue and with other organs acting as a crucial homeostasis regulator. Interestingly, excessive expansion of adipose tissue present in obese people is often accompanied by a chronic inflammatory state, manifested by increased plasma levels of interleukin IL-1β, IL-6 or tumor necrosis factor (TNF). Since MCPIP1 is activated by pro-inflammatory stimuli, including IL-1β, TNF we postulated that it may play an important role in adipogenesis and obesity.

4. Structural analysis of MCPIP1.

The MCPIP family (including MCPIP1, MCPIP2, MCPIP3 and MCPIP4) was first reported to participate in the negative regulation of LPS-induced macrophage activation. Today we know, that MCPIP1 acts as a RNa which significantly shortens the half-life of pro-inflammatory cytokines' mRNA (eg. IL-1β, IL-6 and IL-12β) by directly targeting their 3′-untranslated region. To link MCPIP1 function with its structure functional studies are performed. Experiments have identified several important domains in MCPIP1: CCCH-type zinc finger domain, ubiquitin-associated domains, two proline-rich regions, PilT N-terminus domain (PIN), natively disordered region. Our studies are focused on the role of MCPIP1 domains in the negative regulation of NFκB activity and transcript stability.

5. Molecular background of renal cell carcinoma.

Renal cell carcinoma (RCC) is a common form of urologic tumor representing 3% of total human malignancies. About 30% of patients with newly diagnosed RCC have evidence of metastases at presentation. What is more, renal carcinoma is resistant to radiation and chemotherapies, and at the moment surgery is the only curative option. Proteins involved in regulation of proinflammatory processes are also important modulators of carcinogenesis. Understanding of molecular genetics and molecular pathways involved in the process of RCC progression and metastasis is important for early detection of tumor, prediction of metastasis and the development of innovative treatments.

The major interests of our laboratory are:

i) the fundamental genetics and biology of clear cell renal cell carcinoma (ccRCC)

ii) the characterization of the role of proteins regulating transcript stability in cancer development and invasiveness.

Research methods:

• culture of primary cells and cell lines,
• gene transfer techniques: transfection, transduction,
• siRNA strategy,
• reporter gene assays,
• PCR, real-time PCR, RACE, differential display,
• Western blot, immunoprecipitation assay, immunohistochemical stainings,
• molecular cloning – plasmid and viral vectors,
• detection of mutations, polymorphism analysis and prediction of diseases,
• colorimetric, fluorimetric and luminometric tests: proliferation, migration, viability, apoptosis,
• In vivo models: tumor inoculation,