DNA Sequencing: U-M Poised for Advances in Personalized Medicine

August 11, 2011

Imagine having a serious illness that will respond to drugs specifically tailored to you – taking into account your genetic makeup, your drug tolerance, even your other illnesses. This is an example of “personalized medicine,” and research being conducted at the University of Michigan is bringing this next step in healthcare closer to actual patients every day.

Jay L. Hess, M.D., Carl Vernon Weller Professor and Chair of Pathology, who is heading up the UMHS deployment team in personalized medicine, describes personalized medicine as providing “The right treatment, for the right patient, at the right time.” Much of the basis of personalized medicine comes from genomic sequencing of individual patients. This sequence information is the basis for a revolution in a cancer therapy and will help physicians tackle other illnesses as well. U-M is well poised to make significant contributions in this area and has a long history of breakthrough discoveries in genetics. For example, the genes underlying cystic fibrosis and neurofibromatosis were both discovered at U-M by Dr. Francis Collins in 1989 and 1990 respectively. More recently in 2005, researchers in the Michigan Center for Translational Pathology (MCTP) directed by Dr. Arul Chinnaiyan discovered that the majority of cases of prostate cancer harbor translocations of the TMPRSS gene and ETS family transcription factors.

In addition, the U-M Cancer Center is second only to M.D. Anderson in receiving National Institutes of Health dollars.

But underpinning a lot of these advances – and providing the necessary analysis for researchers – is the University of Michigan’s DNA Sequencing Core, which recently moved to the U-M North Campus Research Complex and underwent a huge growth spurt.

Known around the world for excellent DNA analysis and its helpful website, the Core handles DNA analysis for U-M laboratories, for outside companies and for other universities without such advanced capabilities.

The Core, led by Director Robert Lyons, Ph.D., has long had a stellar reputation for older, well-established forms of DNA analyses. “We are so cost-efficient that many researchers, even those at other universities that have their own DNA analysis facility, preferred to send their work to us,” Lyons says. Recently, therefore, when new methods and instruments emerged, it was only natural to look to Lyons’ group to operate them. The problem was they didn’t have the space.

The Core now occupies a 10,000 square-foot space at NCRC, nearly three times as large as its former locations. Compared to the original DNA laboratory – formed in 1993 in just 450 square feet of lab space – the Core has grown exponentially. Just like the advancements in DNA sequencing itself.

“This space will enable the U-M DNA Sequencing Core to be even more efficient and cost effective by allowing us to grow by bringing in more equipment and more people,” says Lyons.

Specialized Genome Centers used to be a requirement, plus years of effort, in order to sequence the cellular DNA from just one human being. Now the University’s own Core lab is doing them in-house, at the rate of 1,000 each year – and accelerating.

Better yet, by doubling the size of the staff from 12 to 25, Lyons can now begin to offer esoteric services that complete the clinical picture of a disease. A rare, inherited heart condition might reveal insights into the formation of that organ if you can find the DNA mutation that caused it, but add in a complete snapshot of other components of the cell, such as all the RNA types, leading to greater understanding.

The move to NCRC was prompted by the Core’s overwhelming success, which in turn brought it a significant piece of equipment, the Pacific Biosciences ‘RS’, which stands for ‘real-time sequencer,’ potentially a game-changer in the world of DNA analysis. “We wrote a proposal to the Howard Hughes Medical Institute and were one of just five universities in the country that received an award to purchase this instrument,” Lyons says.

The equipment is so promising to the core’s work – and so large – that it demanded its own space, which U-M was more than willing to give.

Because DNA can replicate itself in vitro, it is extremely necessary to have as clean a laboratory as possible. “The larger space also will help us avoid false results from contamination,” Lyons says. “The lab setup here is gorgeous.”