In the News
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.
Oct. 17, 2014 — Children’s Medical Center Research Institute at UT Southwestern has been named by the Dallas Regional Chamber as a 2014 Innovation Catalyst award recipient, given annually to a company or institution that strengthens the region’s capacity for innovation.
Read the news release.
Oct. 9, 2014 — Researchers are just now beginning to appreciate the ways in which differences in protein synthesis among mammalian somatic cells are necessary for tissue development and homeostasis, as new approaches are making it possible to more generally compare protein synthesis and its regulation among different kinds of cells.
Dr. Sean Morrison, Director of the Children’s Medical Center Research Institute at UT Southwestern, is senior author of a review of research that focuses on differences in protein synthesis, protein stability, and ribosome assembly among cells that are critical for tissue development and homeostasis.
The mechanisms that underlie these differences are only beginning to be clarified, but they are already providing fundamental new insights into development, tissue regeneration, and how these processes go wrong in degenerative diseases and cancer.
Read the research review published in Cell.
Aug. 31, 2014 — With nearly 1,500 active clinical trials involving stem cells taking place in the United States, Dr. Sean Morrison, Director of the Children’s Medical Center Research Institute at UT Southwestern and President-Elect of the International Society for Stem Cell Research, says it’s important to appreciate the rigorous process involved in developing successful stem cell therapies.
Read more about the current state of stem cell discovery and treatment development as reported by Healthline.
Aug. 29, 2014 — Hao Zhu, M.D., an Assistant Professor at the Children’s Medical Center Research Institute at UT Southwestern, has been named one of the Dallas 40 by D Magazine. Read the article.
Aug. 11, 2014 — Researchers at the Children’s Medical Center Research Institute at UT Southwestern have identified a gene that contributes to the development of several childhood cancers, in a study conducted with mice designed to model the cancers.
If the findings prove to be applicable to humans, the research could lead to new strategies for targeting certain childhood cancers at a molecular level.
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.
Read the news release.
July 28, 2014 — Hepatocellular carcinoma (HCC) — the most common form of liver cancer — is the third leading cause of cancer-related death in the world, yet there are few effective therapies and virtually no predictive markers based on a molecular understanding of the disease.
To increase current knowledge of HCC genetics, scientists at the Children’s Medical Center Research Institute at UT Southwestern have generated efficient and physiologic liver cancer mouse models with in vivo use of a powerful genome-engineering tool known as Transcription Activator-Like Effector Nucleases, or TALENs.
Read the study published in Cancer Research.
June 20, 2014 — The Children’s Medical Center Research Institute at UT Southwestern (CRI) has identified a biomarker that enables researchers to accurately characterize the properties and function of mesenchymal stem cells (MSCs) as they exist in the body.
MSCs are the focus of nearly 200 active clinical trials registered with the U.S. National Institutes of Health, targeting conditions such as bone fractures, cartilage injury, degenerative disc disease and osteoarthritis. Read the news release.
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.