In the News

In the News

screen-shot-2016-12-08-at-2-25-32-pmDALLAS – Dec. 13, 2016 – A team of scientists at the Children’s Medical Center Research Institute at UT Southwestern (CRI) discovered a new bone-forming growth factor, Osteolectin (Clec11a), which reverses osteoporosis in mice and has implications for regenerative medicine.

Although Osteolectin is known to be made by certain bone marrow and bone cells, CRI researchers are the first to show Osteolectin promotes the formation of new bone from skeletal stem cells in the bone marrow. The study, published in eLife, also found that deletion of Osteolectin in mice causes accelerated bone loss during adulthood and symptoms of osteoporosis, such as reduced bone strength and delayed fracture healing.

Read the news release.

 


osteolectin-reverses-osteoporosisDALLAS – Dec. 13, 2016 – A team of scientists at the Children’s Medical Center Research Institute at UT Southwestern (CRI) discovered a new bone-forming growth factor, Osteolectin (Clec11a), which reverses osteoporosis in mice and has implications for regenerative medicine.

Although Osteolectin is known to be made by certain bone marrow and bone cells, CRI researchers are the first to show Osteolectin promotes the formation of new bone from skeletal stem cells in the bone marrow. The study, published in eLife, also found that deletion of Osteolectin in mice causes accelerated bone loss during adulthood and symptoms of osteoporosis, such as reduced bone strength and delayed fracture healing.

“These results demonstrate the important role Osteolectin plays in new bone formation and maintaining adult bone mass. This study opens up the possibility of using this growth factor to treat diseases like osteoporosis,” said Dr. Sean Morrison, who led the team that made the discovery. Dr. Morrison, CRI Director, holds the Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern Medical Center, and the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at Children’s Research Institute at UT Southwestern.

Osteoporosis, a progressive bone disease characterized by decreased bone mass and an increase in fractures, affects over 200 million people worldwide. Most existing therapies such as bisphosphonate drugs reduce the rate of bone loss, but they do not promote new bone growth. Teriparatide (PTH) is the only agent currently approved for the formation of new bone, but its use is limited to two years due to a potential risk of osteosarcoma.

To determine whether treatment with Osteolectin could reverse bone loss after the onset of osteoporosis, the CRI research team used mice that had their ovaries removed to model the type of osteoporosis that develops in postmenopausal women. Mice were given daily injections of PTH or recombinant Osteolectin. The study found that both recombinant Osteolectin- and PTH-treated mice had significantly increased bone volume compared to untreated mice. Both treatments effectively reversed the bone loss that occurred after the removal of the ovaries.

“These early results are encouraging, suggesting Osteolectin might one day be a useful therapeutic option for osteoporosis and in regenerative medicine,” said Dr. Morrison, also a Professor of Pediatrics at UT Southwestern, a CPRIT Scholar in Cancer Research, and a Howard Hughes Medical Institute Investigator.

Researchers in the Hamon Laboratory for Stem Cell and Cancer Biology, of which Dr. Morrison is the principal investigator, plan to further test Osteolectin’s therapeutic potential and to identify the receptor for Osteolectin, which is key to understanding the signaling mechanisms the protein uses to promote osteogenesis.

The study’s authors are Dr. Rui Yue and Dr. Bo Shen, both postdoctoral researchers at CRI. The project was supported by the Cancer Prevention and Research Institute of Texas (CPRIT) and donors to the Children’s Medical Center Foundation.

About CRI

Children’s Medical Center Research Institute at UT Southwestern (CRI) is a joint venture of UT Southwestern Medical Center and Children’s Medical Center, the flagship hospital of Children’s Health. CRI’s mission is to perform transformative biomedical research to better understand the biological basis of disease. Located in Dallas, Texas, CRI is home to interdisciplinary groups of scientists and physicians pursuing research at the interface of regenerative medicine, cancer biology and metabolism. For more information visit: cri.utsw.edu. To support CRI visit: give.childrens.com/about-us/why-help/cri/.


sean_morrison_phd_20151-copyDr. Sean Morrison, Professor of Pediatrics and Director of the Children’s Medical Center Research Institute at UT Southwestern, received an Individual Investigator Award from CPRIT to study the mechanisms of melanoma metastasis. Dr. Morrison is one of five researchers at UT Southwestern to receive funding from CPRIT.

Dr. Morrison aims to better understand the complex molecular mechanisms that allow cancer cells to spread. This research will build on earlier work that found metastasis of human melanoma cells to be limited by oxidative stress, caused by the generation inside cancer cells of highly toxic reactive molecules known as reactive oxygen species. Most melanoma cells that enter the blood die from oxidative stress. Dr. Morrison believes the rare melanoma cells that survive during metastasis undergo specific metabolic adaptations that allow them to withstand the oxidative stress.

Read the article.


sean_morrison_phd_20151-copyDr. Sean Morrison, Professor of Pediatrics and Director of the Children’s Medical Center Research Institute at UT Southwestern, received an Individual Investigator Award from CPRIT to study the mechanisms of melanoma metastasis. Dr. Morrison is one of five researchers at UT Southwestern to receive funding from CPRIT.

Dr. Morrison aims to better understand the complex molecular mechanisms that allow cancer cells to spread. This research will build on earlier work that found metastasis of human melanoma cells to be limited by oxidative stress, caused by the generation inside cancer cells of highly toxic reactive molecules known as reactive oxygen species. Most melanoma cells that enter the blood die from oxidative stress. Dr. Morrison believes the rare melanoma cells that survive during metastasis undergo specific metabolic adaptations that allow them to withstand the oxidative stress.

Increasing our understanding of these mechanisms is crucial to develop new pro-oxidant therapies that could prevent metastasis by exacerbating oxidative stress or by preventing the metabolic adaptations used by cancer cells to survive during metastasis. This work represents a fundamental shift in strategy away from the use of anti-oxidants for cancer therapy, which appear to promote cancer cell survival and which have been shown in clinical trials to promote cancer progression.

To date, CPRIT has awarded $1.67 billion in grants to Texas researchers, institutions and organizations. The agency began making awards in 2009 after Texas voters overwhelmingly approved a 2007 constitutional amendment committing $3 billion to the fight against cancer.

CPRIT provides funding through its academic research, prevention, and product development research programs. Programs made possible with CPRIT funding have reached all 254 counties of the state, brought more than 129 distinguished researchers to Texas, advanced scientific and clinical knowledge, and provided more than 3 million lifesaving education, training, prevention, and early detection services to Texans, according to CPRIT.


cris-contribution-to-childhood-cancer-research-infographic-finalOctober 11, 2016 – According to statistics from the National Cancer Institute, 10,380 children in the U.S. under the age of 15 will be diagnosed with cancer this year. Although advances in treatment have increased the five-year survival rate from 58 percent to 80 percent, cancer in children remains the leading cause of disease-related death among children and teenagers. But the outlook is improving thanks to cutting-edge biomedical research that contributes to the understanding of the disease and the discovery of new treatment options.

The interdisciplinary group of scientists and physicians at the Children’s Medical Center Research Institute at UT Southwestern (CRI) have made significant strides in childhood cancer research.

Read the article.


cri-childhood-cancer-research

According to statistics from the National Cancer Institute, 10,380 children in the U.S. under the age of 15 will be diagnosed with cancer this year. Although advances in treatment have increased the five-year survival rate from 58 percent to 80 percent, cancer in children remains the leading cause of disease-related death among children and teenagers. But the outlook is improving thanks to cutting-edge biomedical research that contributes to the understanding of the disease and the discovery of new treatment options.

The interdisciplinary group of scientists and physicians at the Children’s Medical Center Research Institute at UT Southwestern (CRI) has made significant strides in childhood cancer research including:

 

Discovering genes that are critical for childhood cancers.

Each year in the U.S., 700 children are newly diagnosed with neuroblastoma, 500 with Wilms tumor and 100 with hepatoblastoma. Finding new treatment methods for these children requires a deeper understanding of how gene expression can fuel cancer development.

Researchers in Dr. Hao Zhu’s lab found that LIN28B – a gene normally turned on in fetal tissues but not in adult tissues – is an important cancer-causing gene in childhood malignancies. Although other groups have shown LIN28B’s involvement in cancer, Zhu’s lab pioneered efforts to understand how this gene functions inside the body of an animal. Focusing specifically on hepatoblastoma, which accounts for nearly 80 percent of all liver tumors in children, researchers investigated how significantly increasing LIN28B or deleting the gene would affect cancer in mice.

They found that overproduction of LIN28B causes hepatoblastoma, while blocking LIN28B impairs cancer growth. LIN28B is a particularly attractive therapeutic target because it is ordinarily only expressed in embryos, so blocking it in children should specifically hinder cancer growth without introducing many unfavorable effects. Knowing pediatric liver cancers depend on this gene opens up the possibility that one day patients could be treated with new strategies other than chemotherapy.

Increasing the safety and effectiveness of bone-marrow transplantation.

Bone-marrow transplants save thousands of lives each year by restoring the blood-forming capacity of patients following chemotherapy or other medical conditions. Bone-marrow transplants are not without risks. It can take months for patients to recover, and in some cases patients may die as a result of infections or other complications. To improve the safety and effectiveness of bone-marrow transplants, investigators must better understand the microenvironment of blood-forming stem cells – the active ingredient in bone marrow transplants.

Historically, little has been known about this microenvironment, but Dr. Sean Morrison and his colleagues have changed that. Over the last five years, they have made several groundbreaking discoveries by characterizing cells and growth factors in the bone marrow that sustain blood-forming stem cells throughout life and regulate the production of blood cells.

They discovered that stem cells live around blood vessels in the bone marrow and that endothelial cells and other stromal cells around the blood vessels make the growth factors that sustain the stem cells. The identification of these cells has made it possible to search for new growth factors in the bone marrow. New growth factors that promote stem-cell function or blood-cell production could accelerate the recovery of patients after bone-marrow transplantation or chemotherapy, shortening their window of vulnerability to potentially life-threatening infections.

The Morrison laboratory has already started to identify such growth factors, and researchers hope to continue to develop new therapeutic approaches that improve the safety of bone-marrow transplants.

Mapping metabolic pathways in cancer to develop better treatment options.

Proper control of metabolism is required for essentially every basic biological process, including cell growth and division. Altered metabolism at the cellular level is a major feature of cancer since tumor cells must reprogram their metabolism to support excessive cell growth. Finding and understanding how these growth-promoting metabolic activities occur in cancer is a key step toward developing new drugs and treatments to inhibit them.

Researchers from Dr. Ralph DeBerardinis’ lab have identified new metabolic pathways that occur when cancer cells rewire metabolic networks to maximize their growth. The DeBerardinis lab has also pioneered techniques to measure cancer metabolism directly in human tumors, providing the most comprehensive and accurate views of tumor metabolism to date.

Traditionally, lung tumors can be diagnosed using a clinical form of glucose imaging called FDG-PET scanning because the ability to take up glucose (sugar) is a well-known metabolic feature of human lung cancer. It was unknown, however, how these tumors used glucose to fuel metabolic pathways. The DeBerardinis scientists mapped the fate of glucose in human lung tumors and identified several metabolic differences between tumors and healthy lung tissue. They also showed that individual tumors, and even regions within the same tumor, used strikingly different metabolic activities to support energy formation.

This led to the development a magnetic resonance imaging technique to predict metabolic behavior in tumors before surgery, providing a completely new approach to study metabolism in human cancer. This work is expected to lead to better ways to exploit metabolic alterations to improve cancer diagnosis and therapy, especially when applied to childhood cancers.


September 22, 2016 – Ralph DeBerardinis, M.D., Ph.D., Director of the Genetic and Metabolic Disease Program at ralph-deberardinis-m-d-ph-d-director-of-the-genetic-and-metabolic-disease-program-at-the-childrens-medical-center-research-institute-at-ut_southwesternthe Children’s Medical Center Research Institute at UT Southwestern (CRI), was among 84 scientists from 43 U.S. institutions chosen as a Howard Hughes Medical Institute Faculty Scholar. The new grant program is a collaboration of HHMI, the Simons Foundation, and the Bill & Melinda Gates Foundation.

Read the article.


September 22, 2016 – CRI Researcher named Howard Hughes Medical Institute Faculty Scholar

ralph-deberardinis-m-d-ph-d-director-of-the-genetic-and-metabolic-disease-program-at-the-childrens-medical-center-research-institute-at-ut_southwesternRalph DeBerardinis, M.D., Ph.D., Director of the Genetic and Metabolic Disease Program at the Children’s Medical Center Research Institute at UT Southwestern (CRI), was among 84 scientists from 43 U.S. institutions chosen as a Howard Hughes Medical Institute Faculty Scholar. The new grant program is a collaboration of HHMI, the Simons Foundation, and the Bill & Melinda Gates Foundation.

The program, a first-time collaboration of the philanthropies, awards grants of $600,000 to $1.8 million over five years to early-career scientists with great potential to make unique contributions to their field. Distinguished scientists evaluated 1,400 applications and selected the Faculty Scholars based on prior research, current investigations, and future potential for bold, innovative investigations.

Dr. DeBerardinis is one of five researchers from UT Southwestern selected to receive this grant. UT Southwestern tied with three other institutions for the second highest number of researchers receiving these awards nationally and had the highest number of awards of any Texas institution.

At CRI, Dr. DeBerardinis studies the metabolic pathways that go awry in cancer and other diseases. He hopes to develop therapeutic agents that selectively manipulate tumor metabolism, reducing tumor growth while leaving the body’s metabolism elsewhere undisturbed. At UT Southwestern, Dr. DeBerardinis also is an associate professor in the Eugene McDermott Center for Human Growth & Development and in Pediatrics, holds the Joel B. Steinberg, M.D., Chair in Pediatrics, and is a Sowell Family Scholar in Medical Research. As a physician-scientist, he also diagnoses and treats children with genetic metabolic disorders at Children’s Medical Center Dallas where he serves as the director of the Division of Pediatric Genetics and Metabolism.

“Ralph is one of the best young cancer metabolism researchers in the country, as well as a clinical leader in the diagnosis and treatment of inborn errors of metabolism in children. He is making transformative scientific discoveries and pioneering new approaches in the clinic,” said Dr. Sean Morrison, CRI Director, Professor of Pediatrics at UT Southwestern, a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research, and an HHMI Investigator. Dr. Morrison holds the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at Children’s Research Institute at UT Southwestern and the Mary


May 10, 2016 — Dr. Bo Zhou, a postdoctoral researcher in the Children’s Medical Center Research Institute lab of Dr. Sean Morrison, has been named the winner of the 2016 Award for Excellence in Postdoctoral Research at UT Southwestern Medical Center. The recognition is the highest annual award given to a UT Southwestern postdoctoral scholar participating in the graduate school’s Postdoctoral Certificate Training Program. Read the article.

Bo-Zhou-2016-Postdoc-Award-web


May 10, 2016 – Dr. Bo Zhou, a postdoctoral researcher in the Children’s Medical Center Research Institute (CRI) lab of Dr. Sean Morrison, has been named the winner of the 2016 Award for Excellence in Postdoctoral Research at UT Southwestern Medical Center.

The recognition is the highest annual award given to a UT Southwestern postdoctoral scholar participating in the graduate school’s Postdoctoral Certificate Training Program. This award recognizes excellent traits of the postdoc such as creativity, productivity, and presentation skills as well as attributes of the postdoc’s research project including originality, depth, and impact.

Dr. Zhou, a graduate of the Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences and one of nearly 600 postdocs on the UT Southwestern campus, won the award in a stringent competition.

“The competition was quite intense, as I had imagined it would be,” said Dr. Zhou, who studies blood-forming stem cells, the most clinically used form of stem cell.

He presented his research at the University Lecture Series on March 2 in the Excellence in Education Foundation Auditorium on the North Campus.

“There are thousands of patients whose lives are saved every year as a result of hematopoietic stem cell (HSC) transplants; however, there are thousands more patients who could be treated more effectively if we could just grow these blood-forming stem cells in culture,” he said. “Despite decades of efforts we are still very limited in our ability to grow and expand these cells in vitro. It is likely that the microenvironment supporting these cells in vivo, called stem cell niche, is not adequately replicated in culture.

“My research aims to unravel the exact cellular composition of the HSC niches in vivo. If I can recreate the niche for HSCs in vitro, it may change how thousands of patients are clinically treated.”

Dr. Zhou, who will return to the his alma mater this summer to take up a faculty position, joined Dr. Morrison four years ago as the Children’s Medical Center Research Institute was coming into being.

“I spent two days in Michigan with him,” Dr. Zhou said, with a smile. “Then I came to Dallas.”

“Bo and another of my postdocs, Dr. Rui Yue, came out of the Chinese Academy of Sciences at the same time,” Dr. Morrison recalled. “They applied to me at the same time. The Chinese Academy of Sciences has a huge number of graduate students, yet Bo and Rui were described to me as the two best scientists to ever train there.

“Losing someone as good as Bo always hurts, but you have to keep in mind that they come here with the goal of launching their own independent laboratory. It makes you feel good when they achieve that goal.”

Dr. Zhou will return to Shanghai with his wife, Dr. Shan Shan Wang, and their 3-year-old son, Evan. The couple met in school at the Chinese Academy of Science. Dr Wang is a postdoctoral researcher in the lab of Dr. Massimo Attanasio, Assistant Professor of Internal Medicine, and in the Eugene McDermott Center for Human Growth and Development.

Finalists for the postdoc award were Dr. Jiangtao Guo, from the lab of Dr. Youxing Jiang, Professor of Physiology, and Biophysics; Dr. Elena Piskounova, also a member of Dr. Morrison’s lab; and Dr. Curtis Thorne, mentored by Drs. Melanie Cobb, Professor of Pharmacology; Steven Altschuler, Professor of Pharmacy at the University of California, San Francisco; and Lani Wu, also Professor of Pharmacy at UCSF.

Requirements to enter the postdoc competition include having produced a first-authored publication from work done at UT Southwestern, as well as letters of recommendation from a mentor, and a collaborator or external referee. Fourteen postdocs representing a dozen labs and nine departments were identified before a pre-award committee made up of faculty members cut the entries in half, then arrived at four finalists, who were interviewed by an awards committee led by Dr. Joel Goodman, Professor of Pharmacology.