Inside CRI, Fall 2015
News from the Children’s Medical Center
Research Institute at UT Southwestern
Shifting landscape for research funding requires new approaches for success
by Sean J. Morrison, Ph.D., Director of the Children’s Research Institute
Most new therapies around the world arose at least in part from research that began in U.S. academic laboratories with work funded by the National Institutes of Health. Despite this record of success, there has been a decline since 2003 in the inflation-adjusted amount of federal funding for NIH from $27 billion to less than $21 billion, eroding the country’s capacity to perform biomedical research. The federal government has, in a sense, abdicated its historical leadership role to fund biomedical research.
Several state governments have been stepping in where the federal government has stepped back. As a result, there will be winner states and loser states that emerge over time. The winner states will be the ones that can afford to make substantial investments in biomedical research, stimulating not only new discoveries but also economic development in their states.
Texas has been at the forefront of this emerging trend in state-level research funding, particularly through its creation in 2007 of the Cancer Prevention and Research Institute of Texas (CPRIT). I was recruited to Texas from Michigan, as were many scientists from other parts of the country, in part because CPRIT funding was available. As of this writing, CPRIT has awarded 900 grants totaling $1.35 billion that are leading to the development of new therapies and the creation of new biotechnology companies in Texas.
Texas is also blessed with tremendous philanthropic support for biomedical research, especially in Dallas, where the philanthropic community very strongly supports the academic research institutions located here. That kind of support is vital to the Children’s Research Institute at UT Southwestern (CRI).
Most people are not familiar with how an institute like CRI works. The funding we receive from Children’s Medical Center Dallas and the Children’s Medical Center Foundation goes almost entirely to recruit faculty, build out the facilities, pay our space costs, get the labs off the ground, and maintain a modest administrative infrastructure.
The vast majority of research at CRI is paid for by extramural grants that come from sources like NIH, CPRIT, the Howard Hughes Medical Institute, and private foundations such as the American Cancer Society. It is a testament to the quality of faculty we have recruited to CRI that they have already successfully competed for nearly $50 million in extramural grant support in only four years of operation.
When I started CRI, I wanted to create an environment that would be nimble enough to accelerate the development of new therapies by better understanding the biological basis of disease. The question was how.
At CRI, one of the approaches we have taken is to create a Clinical Innovation Fund that our researchers can turn to for financial support to test ideas through early-stage clinical trials. These are the kinds of ideas that existing sources of funding, like NIH, aren’t good at supporting.
When we have an opportunity to translate discoveries to benefit patients, we don’t want to wait a year or two while our investigators write grants. Clinical Innovation Fund proposals are presented to CRI’s External Scientific Advisory Board, comprised of some of the most successful senior scientists from around the country, who determine which ideas deserve to be tested.
In today’s funding environment, the future success of biomedical research institutes in the United States will be influenced by how they are structured. Institutes across the country have a responsibility to approach biomedical research in creative ways, so that in 15 years people can look back and point to important discoveries and treatments that wouldn’t have been achieved otherwise.
CRI researchers develop new techniques to study stroke damage and repair
Each year in the United States, nearly 130,000 people die as a result of a stroke. Dr. Woo-Ping Ge’s laboratory at the Children’s Research Institute at UT Southwestern (CRI) has made significant progress researching brain repair following a stroke, specifically ischemic strokes that occur when blood to the brain is temporarily blocked.
“When we began our research, there weren’t any existing methods to precisely produce a very small stroke in the brain of a mouse for our studies,” says Dr. Ge. “We now have developed a method by which we can use a very small magnet and magnetic nanoparticles to control the blood flow into the brain in mouse blood vessels that are thinner than a human hair. As a result, using our leading-edge imaging techniques, we are able to study at the cellular level the injury that takes place from an ischemic stroke as well as the repair.”
Dr. Ge and his team have found that in young mice, for example, about half of the smooth muscle cells that control the blood flow die within one hour following a stroke, while in adult mice the smooth muscle cells don’t die but instead contract. There are seven other types of cells in the area of the brain affected by ischemic stroke, and the Ge Lab will study each of them one at a time to obtain a complete picture of how the brain repairs itself.
“Because we are part of CRI, my lab will be able to leverage the genomics and flow cytometry facilities here to sort the cells that have been affected by stroke in young and adult mice, and then identify the genetic differences between those cells to determine why they react differently following a stroke,” says Dr. Ge. “Hopefully within the next year we will have enough data on how the cells affected by stroke respond during the repair process, which will bring us closer to identifying therapeutic targets to combat cell death in patients who suffer a stroke.”
CRI scientists see through bones to uncover new stem cell data
A team of scientists led by Dr. Sean Morrison at the Children’s Research Institute at UT Southwestern (CRI) has become the first to use a tissue-clearing technique to localize a rare stem cell population, in the process cracking open a black box containing detailed information about where blood-forming stem cells are located and how they are maintained. The findings, published in Nature, provide a significant advance toward understanding the microenvironment in which stem cells reside within the bone marrow.
As part of the advancement toward growing blood-forming stem cells in culture, the CRI team’s work yielded new findings and confirmed others: blood-forming stem cells tend to be clustered in the center of the bone marrow, not closer to bone surfaces as some had previously thought; blood-forming stem cells are indeed associated with sinusoidal blood vessels; and there are no spatially distinct niches for dividing and non-dividing blood-forming stem cells.
CRI student profile: Liem Nguyen
When Liem Nguyen was growing up in Vietnam, he was fascinated by the stories his father, a virologist, would tell him about immune cells — how they were like little soldiers fighting against bacteria and viruses. Today, Nguyen is a Howard Hughes Medical Institute International Predoctoral Fellow at the Children’s Research Institute at UT Southwestern (CRI), the first Vietnamese student to have received the prestigious award.
At CRI, Nguyen is pursuing his Ph.D. in Dr. Hao Zhu’s laboratory, where he is researching ways to inhibit liver cancer development, including pediatric liver cancer, at the molecular level. He recently was co-first author for a research paper published in Cancer Cell that pinpointed a specific gene, Lin28b, as a significant contributor to several childhood cancers.
Nguyen says his goal as a scientist is twofold: to help solve the puzzle of cancer by making discoveries that have the potential to revolutionize the way cancer is treated; and to contribute to a positive image for his country of birth by making significant achievements in science and medicine.