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Inside CRI: Spring 2016

Scientists must play a leading role to ensure breakthrough advances are safe, effective and ethical

 Sean J. Morrison, Ph.D., Director of the Children’s Research Institute

As I end my term as President of the International Society for Stem Cell Research (ISSCR), I can’t help but reflect on the challenges presented by a fast-moving field with unprecedented potential to transform human health. The field of stem cell research is advancing more quickly than anyone expected, and new technologies that were unimagined even five years ago have caused us to reimagine what the future of medicine will look like.

Several new cell therapies are already in clinical trials for major public health problems, and new molecular biology techniques have made it possible to correct genetic errors with shocking efficiency. Along with these new technologies come new questions. Most importantly, how should we regulate clinical testing to ensure new therapies are safe and effective while also accelerating their delivery?

Every time a new technology emerges in medicine, a paralyzing uncertainty arises about how the new technology should be tested to ensure it is safe, effective, and ethical. In the absence of an authoritative answer to these questions, every institution struggles to come up with its own answers. In the area of regenerative medicine, ISSCR has stepped into this leadership vacuum by offering Guidelines for Stem Cell Research and Clinical Translation. We published the first editions of these guidelines in 2006 and 2008. In May we released an updated version to address the new technologies and questions nobody could have imagined in 2008. These new guidelines are currently being implemented globally.

To craft these guidelines the ISSCR brought together the world’s leading experts to discuss burgeoning issues such as germline genome modification, autologous stem cell transplantation, and the regulation of clinical trials in regenerative medicine. In the area of germline genome modification, new molecular biology technologies have created the potential to fix genetic defects in human embryos. On one hand, few would oppose permanent cures for fatal inherited diseases, such as beta-thalassemia, in embryos during fertility treatment.

On the other hand, these technologies would irreversibly change not just the genetic makeup of one person, but all of their descendants. In our view, we don’t yet understand these technologies well enough to know if they can be used safely. As a consequence, ISSCR has recommended that research continue but that there should be a moratorium on any clinical use of germline genome modification in human embryos until more data can be gathered and we can have a wider discussion of the appropriate uses of this technology.

While ISSCR has sometimes advocated for less government regulation to accelerate regenerative medicine, in other cases we have advocated for more regulation. Snake oil salesmen across the world have attempted to exploit the hopes of desperate patients by selling unproven “stem cell therapies” that have not been tested in clinical trials and are often implausible based on our understanding of the science.

A key priority of ISSCR is to speak out against these unproven therapies and against lax government regulation that allows sales of snake oil to flourish, particularly in countries without effective Food and Drug Administrations. Partly as a result of ISSCR’s advocacy and guidelines, China has cracked down on unproven stem cell clinics, and efforts to water down FDA regulation of regenerative medicine in the U.S. have so far stalled.

As the pace of discovery and clinical application continues to quicken, it is important to remember that the goals for stem cell research remain the same: to improve our understanding of the biological basis of disease and to develop new treatments to improve human health. When it comes to moving forward with new therapies and technologies, our society will succeed or fail based on how well it balances the need to ensure safety and effectiveness with the desire to accelerate the delivery of cures.

As ISSCR has done in developing the Guidelines for Stem Cell Research and Clinical Translation, it is more important than ever that scientists engage these critical issues and explain them to the public and to policy makers. Policies that are not based on a sound understanding of the science will inevitably delay the development of new therapies and fail to advance human health.

CRI research opens new doors to better targeting of lung cancer

Seeking to find a way to exploit cancer metabolism to predict disease progression, Dr. Ralph DeBerardinis and his team at CRI partnered earlier this year with Dr. Robert Lenkinski, Professor of Radiology and Dr. Kemp Kernstine, Professor and Chief of the Division of Thoracic Surgery at UT Southwestern to pioneer a new method for conducting in-depth research on malignant tumors in patients. In the process, Dr. DeBerardinis uncovered new complexities underlying cancer biology and overturned a nearly century-old perception about cancer metabolism.

Dr. DeBerardinis’ study, published in Cell, may pave the way for opportunities to identify new treatments for lung cancer.

CRI researchers link absence of protein to liver tissue regeneration

A research team at CRI led by Dr. Hao Zhu recently found that inactivating a certain protein-coding gene promotes liver tissue regeneration in mammals, providing new ideas about how to treat liver damage or chronic liver disease.

“Following repeated injuries, cirrhosis or scar tissue forms, greatly increasing the risk of cancer,” says Dr. Zhu, an Assistant Professor at CRI, Assistant Professor in Internal Medicine and Pediatrics at UT Southwestern Medical Center, and a CPRIT Scholar in Cancer Research. “However, we discovered that the livers of mice lacking a gene known as Arid1A were resistant to tissue damage and healed better than mice with the gene.”

On observation, livers in the mice without the gene appeared healthier, and blood tests confirmed improved liver function. When researchers deleted the gene in mice with various liver injuries, they found that the livers replaced tissue mass quicker and showed reduced fibrosis in response to chemical injury. Also, other tissues such as wounded skin healed faster in Arid1a-deficient mice.

“We want to identify small molecules that mimic the effect of these genetic findings,” says Dr. Zhu. “The ideal drug would be one that helps the liver heal while inhibiting the development of cancer. That would be the perfect drug for my patients.”

The study was published in the journal Cell Stem Cell.

CRI postdoc profile: Elena Piskounova, Ph.D.

Dr. Elena Piskounova clearly remembers the moment as a teenager when she decided she wanted to pursue a career as a scientist. She was watching the film, The Race for the Double Helix, starring Jeff Goldblum as Jim Watson, who along with Francis Crick discovered that DNA exists in the form of a three-dimensional double-helix.

During one of the movie’s most dramatic moments, the two scientists were engaged in an animated back-and-forth discussion while walking down a crowded street. Dr. Piskounova thought to herself, “I want to be able to do that!”

Fast forward to 2016, and Dr. Piskounova, who received her Ph.D. in biological and biomedical sciences from Harvard, is finishing up her postdoctoral fellowship in Dr. Sean Morrison’s lab at CRI. She recently was first author of an important study showing that cancer cells benefit more from antioxidants than normal cells, raising concerns about the use of dietary antioxidants by patients with cancer.

The work described in the video was published in the leading international science journal, Nature. Dr. Piskounova’s work at CRI was funded by an HHMI Fellowship of The Helen Hay Whitney Foundation.

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