Interview with Kevin Hrusovsky part 1: molecular interactions of a disease
Rebecca Aris interviews Kevin Hrusovsky
As our personalized medicine month continues we speak with Kevin Hrusovsky in this first of a three part interview. Here Kevin highlights the most exciting recent advances in understanding of molecular interactions of disease.
Recently we have seen some very exciting breakthroughs in our understanding of the fundamental molecular interactions of diseases, notably in breast cancer and genetic disease.
We interviewed Kevin Hrusovsky to find out more. Kevin is President of Life Sciences and Technology (LST) at Perkin Elmer – a leading edge personalized medicine / health technology division and former CEO of Caliper Life Sciences acquired by PerkinElmer late last year. LST aims to revolutionize global personalized health by facilitating early detection, next generation treatment and ultimately prevention of diseases.
Kevin speaks with pharmaphorum about recent breakthroughs in the understanding of molecular interactions of disease.
RA: What recent advances in understanding molecular interactions of a disease are you most excited about?
Advance #1: Non-Coding (“Junk”) DNA and Epigenetics:
Until recently, it was believed that of the 3 billion bases pairs that make up the human genome, only the 2% that encodes proteins was important for disease. The other 98% was dismissed as “junk” and wasn’t thought to have much clinical value.
A few weeks ago, a landmark study gave us “the Encyclopedia of DNA Elements” – or ENCODE for short. This was a unified global sequencing effort which revealed that more than 80% of the genome is functional and potentially plays a role in disease – it turns out that most of the genome plays an important role in regulating the 2% of coding DNA.
Think of it as a sophisticated master control switch, comprised of about 4 million switches, that determine our health. In fact, genetic changes in this non-coding region is linked to >,400 common diseases. To put it another way, the majority of the human genome, which we dismissed for decades as “junk”, is incredibly important to our health and well being.
“To put it another way, the majority of the human genome, which we dismissed for decades as “junk”, is incredibly important to our health and well being.”
This just underscores how new and unexplored the field of genomics is from a medical perspective – which means that the best and most exciting findings are still ahead of us.
Also, it underscores the importance of epigenetics and the environment. Here we are seeing new evidence at the molecular mechanism level that shows how closely the environment is tied to our health. Think about it – 4 million switches, most of which involve epigenetics. While we don’t yet have a clue how most of them are involved in disease, once we have figured it out the clinical implications will be tremendous in terms of disease diagnosis and treatment – and eventually, prevention.
Advance #2: Integration of Omics and the Power of informatics
While I am excited by the amazing progress we have seen in next generation sequencing (NGS) is terms of speed, scope and cost, I am even more excited by the prospect of being able to combine genomic sequence data with other omics data and gain entirely new insights into many diseases.
“…the clinical implications will be tremendous in terms of disease diagnosis and treatment – and eventually, prevention.”
Just a few weeks ago, there was an incredible breakthrough in our understanding in breast cancer, thanks to the efforts of the Cancer Genome Atlas Network. They looked at 825 human breast cancers and then did a massive and truly impressive analysis of data from 5 different platform technologies:
1) genomic DNA copy number arrays.
2) DNA methylation.
3) next generation sequencing (exome sequencing).
4) mRNA arrays.
5) proteomic arrays.
Combining this multi-platform data set with powerful informatics, the study showed that:
1) breast cancer has 4 main classes according to genetic / epigenetic abnormalities.
2) each of the 4 classes has significant molecular heterogeneity.
3) somatic mutations (acquired during life, not inherited) occurred in 3 genes at >,10% incidence: PIK3CA, TP53, GATA3.
4) there is a link between ovarian cancer and one of the breast cancer classes, which suggests these different tumor types may be treatable with the same drug. This underscores the notion that we should look at cancers by their molecular makeup, rather than their organ / tissue type, which in turn ties into personalized cancer medicine. By knowing which specific mutations a cancer has, whether it’s breast or ovarian, we can select the best targeted therapy to thwart that tumor.
In addition to providing molecular insight that fundamentally changes our understanding of breast cancer, this study highlights the important power of combining and analyzing multifaceted data using bioinformatics, a critical tool that is key to turning massive amounts of biological data into actionable information that results in better diagnosis and treatment.
The next part of this interview can be viewed here.
About the interviewee:
Kevin Hrusovsky was appointed President, Life Sciences and Technology, Perkin Elmer in November 2011, following the acquisition of Caliper Life Sciences. In addition to leading the Life Science segment of PerkinElmer, he is also responsible for Services for LST products and Informatics, which was recently moved into LST.
The union of PerkinElmer and Caliper brought together many innovative technologies which, when combined, offer what Hrusovsky believes is a remarkably comprehensive and disruptive portfolio that enables translational medicine and personalized health.
A key part of the mission at LST is to revolutionize global personalized health by facilitating early detection, next generation treatment and ultimately prevention. Importantly, given PerkinElmer’s long track record as a leader in environment health, the Company’s view that helping to sustain the earth’s ecosystem is integral to our goal of preventing and eradicating disease. As part of the drive towards personalized health, earlier this year PerkinElmer announced a new initiative – the creation of Centers of Personalized Health Innovations (cPHI). The first cPHI facility is currently being built in Hopkinton, Massachussetts, and is scheduled to be complete by mid-2013. Through these Centers, PerkinElmer will be able to leverage our innovative strengths in imaging, microfluidics, next generation sequencing, biotherapeutics, epigenetics, companion diagnostics and informatics, with a focus on enabling.
What recent advances in understanding disease molecular interactions have you noted?