Yasser Riaz Alhosseini
Assistant Professor, Department of Human Genetics
Investigator, Victor Phillip Dahdaleh Institute of Genomic Medicine
While collaborating on genome characterization of different tumor entities, research in the lab is focused on following topics:
Comprehensive molecular understanding of renal cell carcinoma
Renal cell carcinoma (RCC) is the most common form of kidney tumors. RCC has different subtypes with clear cell (ccRCC; conventional) being the most frequently diagnosed subtype accounting for 75-80% of RCCs. The incidence of RCC is increasing worldwide, but there is no biological marker for routine clinical use. Furthermore, it is essential to identify novel therapies as RCCs are resistant to conventional chemo- and radio-therapy.
We have recently generated comprehensive genome, epigenome and transcriptome landscapes of ccRCC. In an integrative manner, our lab is dissecting these profiles in order to identify molecular aberrations that possess cancer-driving activities. We have also extended our research to characterize molecular aberrations of other subtypes of RCC including papillary and chromophobe tumors, whose genetic abnormalities are less understood.
Post-transcriptional regulatory programs in cancer
In parallel to analyzing (epi)genome patterns, as factors governing gene expression at transcriptional level, we are investigating role of non-coding transcripts including long non-coding RNAs and microRNAs (miRNAs) as well as RNA binding proteins (RBPs) in post-transcriptional deregulation of cancer transcriptome. Specifically, we combine cancer-associated gene expression patterns with regulatory networks of miRNAs and RBPs, and apply quantitative approaches to these profiles in order to predict factors whose aberrant function can explain the abnormal transcriptome of tumor samples. These potentially 鈥渕aster regulators鈥� are then subjected to experimental verification for their driver activities.
Investigating intra-tumoral heterogeneity and its contribution to metastasis
Approaches to stratifying risk or tailoring therapy for individual cancer patients based on the molecular profile of their tumor biopsy are complicated by the existence of genetic heterogeneity (representing distinct populations of cancer cells with different sets of mutations; subclones) both within and across tumors. Furthermore, across tumor sites, genomes of disseminated cancer cells may have similarities at the onset of metastatic disease, but substantial changes in the genetic composition occur spatially and over time, supporting the suggestion that the expansion of aggressive driver clone(s) and the emergence of relevant subclones correlate with development of incurable disease and potential therapeutic resistance. Our lab has optimized protocols of NGS on minutes amount of DNA as well as on DNA isolated from Formalin-fixed, paraffin-embedded (FFPE) samples providing an opportunity to analyze archived primary tumors of patients affected with metastatic or recurrent disease. We analyze the heterogeneous clonal composition of primary and metastatic tumors in order to investigate genomic evolution of metastasis.
