The study molecular mechanisms of human biology and disease with Philipp Kapranov
Philipp Kapranov, Director of Genomics Research, St. Laurent Institute, a non-profit dedicated to studying molecular mechanisms of human biology and disease joins eHealth Radio and the Health News Channel.
Listen to interview with host Eric Michaels & guest Philipp Kapranov discuss the following:
What is the science of genomics?
Can genomics revolutionize medicine and how we treat diseases?
What is RNA? Why do we always focus on DNA?
What is genomic dark matter and what is dark matter RNA?
What are you currently working on?
Conclusion: Human body is made of cells. Each cell is like a huge city but instead of people its made of millions of small molecular machines. There are different types of machines – some are used to store information, some are used to read it out and convey it to other parts of the cell, to make other machines, to control other machines, for energy production, movement, making the structure of the cell, defense etc. All these machines function in networks just like humans form teams and social groups. Each such city operates because all of its machines work together based on a program stored in our DNA and read out in the form of RNA. Understanding disease would mean understanding the program itself, how its readout and how the networks of these molecular machines function.
My primary research interest includes systems biology and genomics in the context of gene expression and discovery of new RNA species (both protein-coding and non-coding) and their functions, especially in the context of human disease, particularly cancer.
In the past 10+ years my research at Affymetrix, Helicos BioSciences, and St. Laurent Institute has focused on the basic scientific question of how much of our genome is functional. I began to answer to this question in 2002 (Kapranov et al, Science 2002) with the unbiased mapping of transcribed regions on human chromosomes 21 and 22, which revealed a vast amount of transcriptional output from non-exonic regions in the time when the output of our genome was considered to be “just 20 thousand protein-coding genes”. I followed this by showing that our genome produces vast amount of non-coding RNAs (Kapranov et al, Science 2007) often belonging to classes previously ignored by the prevalent opinion at the time, such as non-polyA and nuclear RNA (Cheng, Kapranov et al, Science 2005; Kapranov et al, Science 2007), and short RNAs (Kapranov et al, Science 2007). This work resulted in the discovery of an un-expectedly complex transcriptional activity of the human genome encompassing several new classes of RNA as well as a highly complex, overlapping organization of functional elements in the genome (Kapranov et al, Genome Research 2005). These discoveries have significantly impacted our understanding of the genomic organization and architecture, while redefining the importance of the so called “junk DNA” and, on a conceptual level, the definition of “gene” (Kapranov et al, Nature Reviews Genetics 2007).
More recently, I have shown using Helicos single-molecule sequencing platform that the genome’s “dark matter” i.e., regions of the genome (~98% of the entire genome) that are transcribed, but do not encode proteins - is read out in the form of RNA and these RNA molecules are common and highly abundant in cells (http://www.ncbi.nlm.nih.gov/pubmed/21176148). Although we do not yet understand the function of this RNA, the very fact that it so abundant suggests that it is functional. These findings were later confirmed and expanded by the ENCODE consortium and are considered the dogma in the field. Also, they have been chosen as one of the top 10 discoveries of the last decade by Science magazine: http://www.sciencemag.org/content/330/6011/1614.full. Most recently, I have identified a novel and ubiquitous class of very long non-coding RNAs (vlincRNAs) in the mammalian genome. A subclass of vlincs controlled by promoters with endogenous retroviruses is upregulates in pluripotent and cancerous cells providing a unique window into the involvement of these previously ignored portions of our genome in development and disease.
My primary areas of expertise include genomics, molecular biology and gene expression. I have an extensive knowledge of microarrays and next-generation sequencing platforms, specifically single-molecule sequences as well as the analysis methods required to extract biologically-meaningful information from the large genomics datasets that are generated by these technologies. I have extensive experience working on projects that combine molecular biology, informatics, and engineering and managing such cross-disciplinary projects.
Overall, I have co-authored 66 peer-reviewed articles published in journals indexed in PubMed, including 7 in Nature (2 as the first author or co-author) and 5 in Science (3 as the first author or co-author). My H-index for the last 5 years (since 2008) is 29, G-index is 30 and I have 8,557 citations during that time frame. For the entire career, my H-index is 32, G-index is 80 and I have 11,281 citations. This information is available at my Google Scholar profile at http://scholar.google.com/citations?user=OPBEW2QAAAAJ.