Research team Weng-Onn Lui
Small RNAs in cancer development
Our main goal is to understand small RNA-mediated gene regulation in human cells, with focus on its role in cancer development and progression. The objectives of our studies are to identify specific small RNAs involved in specific cancer types, to characterize their functions and to elucidate the molecular mechanism involved in tumorigenesis and progression.
Since the discovery of RNA interference, efforts to identify endogenous small RNAs (~18-30 nucleotides in length) have led to the discovery of several distinct classes of small RNAs in various organisms. These small RNAs function by guiding sequence-specific gene silencing, at the transcriptional and/or post-transcriptional level, and have been shown to play important regulatory roles in diverse biological processes.
Our strategies combine clinical and molecular analysis of clinical specimens and functional analysis in experimental systems. Three main ongoing projects are described below:
Cutaneous melanoma is a common and aggressive form of skin cancer with a rising incidence. Despite improvements in early melanoma diagnosis, the 5-year survival rate still remains low. Therefore, novel biomarkers are urgently needed to devise new means of detection and treatment. In this project, we are exploring the prognostic value of microRNA (miRNA) profiling in cutaneous melanoma.
We are also elucidating the role of several miRNAs in melanoma development, using a combination of biochemistry and molecular biology techniques, as well as clinically relevant experimental systems.
2) Small RNAs in viral oncogenesis
Given that numerous viruses are capable to encode small modulatory RNAs, the changes in endogenous miRNA pattern and tumor-related roles for miRNAs have been demonstrated, we hypothesize that miRNAs might be involved in the host cell response to viral infection and/or viral induced cellular transformation leading to cancer development. Our goal is to dissect the molecular events by which virus infects cells and initiates transformation. We are examining host miRNAs and viral factors, as well as the effects of miRNAs on gene regulation involved in viral infection and carcinogenesis. Particularly, we are focusing on two types of cancer, i.e., human papillomavirus-associated cervical cancer and Merkel cell Polyomavirus-associated Merkel cell carcinoma.
3) Adrenal cortical cancer
Adrenal cortical cancer (ACC) is a rare form of aggressive cancer with a poor prognosis. Although recent genomic studies of ACCs have contributed to our understanding of the disease, both diagnostic and prognostic assessments remain challenging issues that need to be resolved. The aim of this study is to identify molecular signature of malignancy based on miRNA expression profiling, and to determine the role of specific miRNA in the development of ACC. Current efforts are directed to analyzing the biological function of several candidate miRNAs in ACC development, which may lead to the identification of an important target for clinical intervention in ACC.
Cancer Center Karolinska, Karolinska University Hospital-Solna R8:04, SE-171 76 Stockholm, Sweden
Phone: +46-8 5177 3930 or +46 8 5177 3616
Weng-Onn Lui, PhD, Associate professor, Team leader
Hong Xie, PhD, postdoc
Pinar Akcakaya, PhD, postdoc
Mahmut Deniz Özata, BSc, PhD student
Roger Chang, MSc, PhD student
Satendra Kumar, MSc, PhD student
Wen-Kuan Huang, MD, PhD student
Previous team members
Stefano Caramuta, PhD, Postdoc
Patrick Scicluna (MSc, Lund University, 2011)
Amani Al-Khalfi (MSc, KI, 2009)
Mohammed Ferdous-Ur Rahman (MSc, KI, 2010)
Vijay Joshua Balasingh (MSc, KTH, 2010)
Ram P. Yadav (MSc, Uppsala University, 2010)
Iryna Kolosenko (MSc, KI, 2009)
The present research is generously supported by grants from:
- The Swedish Research Council
- The Swedish Cancer Society
- Karolinska Institutet
- Stockholm County Council
- The Cancer Research Foundations of Radiumhemmet