Ralph DeBerardinis Laboratory
In the News
October 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.
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September 22, 2016 – Ralph 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.
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April 7, 2016 — Scientists at the Children’s Medical Center Research Institute at UT Southwestern have identified a novel metabolic pathway that helps cancer cells thrive in conditions that are lethal to normal cells. Read the news release.
Feb. 26, 2016 — Because of the foresight and generosity of several of Dallas’ leading foundations, more than $30 million has recently been committed to Children’s Medical Center Foundation to catapult the Children’s Medical Center Research Institute at UT Southwestern into a leader in pediatric research.
- Read the news release.
- Read the article in the Dallas Morning News.
- Read the article in D Healthcare Daily.
Feb. 4, 2016 — Scientists at the Children’s Medical Center Research Institute at UT Southwestern have pioneered a new method for conducting in-depth research on malignant tumors in patients, in the process discovering new complexities underlying cancer biology and overturning a nearly century-old perception about cancer metabolism.
The findings, published in Cell, may pave the way for exploiting cancer metabolism to predict disease progression and treat cancer. Read the news release.
Nov. 3, 2014 — Scientists at the Children’s Medical Center Research Institute at UT Southwestern (CRI) have identified a metabolic pathway that allows cancer cells to survive periods of stress brought on by blocking the major pathway by which cells produce energy.
Most cells survive and grow by oxidizing glucose. This pathway involves first converting glucose into a smaller molecule called pyruvate, then importing the pyruvate into the mitochondria where it supplies pathways that provide energy and building blocks for growth.
CRI researchers led by Dr. Ralph DeBerardinis sought to understand whether transfer of pyruvate into the mitochondria is required for cancer cell survival and growth. They determined that although blocking pyruvate entry did, as expected, compromise the energy state of the cell, it simultaneously activated a second pathway fueled by the amino acid glutamine.
This new pathway provided enough flow of mitochondrial metabolism that cancer cells were able to survive and, to some extent, continue to grow. The glutamine-dependent pathway involved activation of an enzyme, glutamate dehydrogenase, which was normally suppressed in cells importing pyruvate into the mitochondria.
The CRI research team used models of brain and lung cancer cell growth to demonstrate that blocking either mitochondrial pyruvate import or glutamate dehydrogenase alone was fairly well tolerated. However, blocking both pathways rapidly led to cancer cell death.
Similarly, treating mice with inhibitors of both activities simultaneously — but not either one alone — significantly reduced tumor growth. Because many solid tumors, like those in the brain and lung, likely contain regions in which access to glucose or pyruvate is compromised, the new glutamine-dependent pathway may provide a survival mechanism to avoid tumor cell starvation. If so, then blocking glutamate dehydrogenase or other steps in the pathway may provide a therapeutic benefit.
July 29, 2014 — The Howard Hughes Medical Institute has awarded nearly $5 million in research fellowships to 46 predoctoral students from 24 countries, including two Ph.D. student researchers at the Children’s Medical Center Research Institute at UT Southwestern — Liem Nguyen and Xiaolei Shi.
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May 22, 2014 — In a breakthrough discovery at the Children’s Medical Center Research Institute at UT Southwestern (CRI), a research team led by Ralph DeBerardinis, M.D., Ph.D., has taken a significant step in cracking the code of an atypical metabolic pathway that allows certain cancerous tumors to thrive, providing a possible roadmap for defeating such cancers.
Following up on Dr. DeBerardinis’ landmark finding in 2011, this most recent discovery identifies the triggering mechanism that plays a key role in causing a series of energy-generating chemical reactions known as the Krebs cycle to run in reverse. Read the news release.
Oct. 24, 2013 — A group of researchers including Ralph DeBerardinis, M.D., Ph.D., Director of the Genetic and Metabolic Disease Program at the Children’s Research Institute at UT Southwestern, have identified new therapeutic targets for a significant percentage of patients who have the most common form of lung cancer among smokers, non-smokers and people under age 45. The targets were detected in spite of the myriad difficulties posed by genetically complex tumor lesions that have hindered efforts to identify therapeutic opportunities. Read the research published in Cell.
Sept. 3, 2013 — Glutamine is an abundant and highly versatile nutrient whose metabolism has implications for tumor cell biology, making it an appealing target for new clinical strategies to detect, monitor and treat cancer. Ralph DeBerardinis, M.D., Ph.D., Director of the Genetic and Metabolic Disease Program at the Children’s Research Institute at UT Southwestern (CRI); Ajla Wasti, M.D., a clinical fellow at CRI; and Chris Hensley, an M.D./Ph.D. student at CRI, have evaluated the metabolic functions of glutamine and its involvement in supporting tumor malignancy, in an effort to better understand how the information could be used in clinical oncology. Read their research review published in The Journal of Clinical Investigation.