Sanford Burnham Prebys Medical Discovery Institute

Scientists at McGill University have uncovered a hidden molecular “switch” that turns on a powerful calorie-burning system in brown fat — the body’s heat-generating fat linked to metabolism and weight control. The breakthrough centers on glycerol, a molecule released when fat is broken down in the cold, which activates an enzyme called TNAP and triggers an alternative heat-producing pathway that scientists had struggled to explain for years.Scientists have uncovered a molecular "switch" in mice that turns on a hidden energy-burning system inside brown fat, a discovery that could eventually help researchers develop new treatments for bone disease. The findings, published in Nature, provide new insight into how brown fat works. Unlike white fat, which stores energy, brown fat burns calories to generate heat. Scientists long believed this heat production depended on a single biological pathway. In recent years, however, researchers identified a second pathway operating alongside the original one, but they did not know what activated it. A team led by Lawrence Kazak at McGill University's Rosalind and Morris Goodman Cancer Institute has now identified the molecular trigger for this alternative system, known as the futile creatine cycle. Scientists Identify Brown Fat "On Switch" When the body is exposed to cold temperatures, it breaks down stored fat to create heat. That process releases glycerol, a molecule produced during fat metabolism. Working with McGill structural biologist Alba Guarné, Canada Research Chair in Macromolecular Machines in DNA Damage and Repair, the researchers discovered that glycerol binds to an enzyme called TNAP in a region they describe as the glycerol pocket. This interaction activates the alternative heat-producing pathway. "This is the first time we've identified how an alternative heat-producing pathway is activated, independent of the classic system," said Kazak, Associate Professor in the Department of Biochemistry and the Canada Research Chair in Adipocyte Biology. "That opens the door to understanding how multiple energy-burning systems work together to keep the body warm at the just-right temperature." Discovery May Advance Bone Disease Research Brown fat has attracted attention for its possible role in metabolism and obesity research. While the new findings could eventually contribute to those areas, the researchers say the most immediate significance may involve bone health because TNAP already has a well-established role in bone formation. The TNAP enzyme is essential for calcification, the process that builds and maintains strong bones. Mutations that reduce TNAP activity can cause hypophosphatasia, a rare disorder sometimes called "soft bones." The condition can lead to fractures, chronic pain, and skeletal abnormalities. Certain inherited mutations have made the disorder more common in parts of Canada, including Quebec and Manitoba. By studying TNAP mutations in laboratory experiments, the scientists discovered that the same molecular switch involved in energy-burning fat cells also directly affects cells responsible for bone mineralization and hardening. The work builds on earlier research by McGill co-author Marc McKee and co-author José-Luis Millán of the Sanford Burnham Prebys Medical Discovery Institute. Their previous efforts helped produce a first-in-class enzyme replacement therapy designed specifically for hypophosphatasia patients with defective TNAP enzymes. "This finding opens the door to a new kind of treatment, where increasing the activity of the TNAP enzyme through its glycerol pocket by natural or synthetic bioactive compounds could potentially boost the beneficial actions of the enzyme in patients, to help restore deficient bone mineralization to healthy levels," said McKee, Professor in the Faculty of Dental Medicine and Oral Health Sciences and the Faculty of Medicine and Health Sciences, and Canada Research Chair in Biomineralization. Researchers have already identified dozens of possible drug candidates for future investigation. About the Study The study, "Glycerol-driven TNAP activation in thermogenesis and mineralization," by Mohammed Faiz Hussain, Lawrence Kazak et al., was published in Nature. The project included collaborations with scientists from Queen Mary University of London, Northeastern University, the Sanford Burnham Prebys Medical Discovery Institute, and the Maine Health Institute for Research. Funding came from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, and the Fonds de recherche du Québec -- Santé.

LA JOLLA, Calif., May 5, 2026 /PRNewswire/ -- Sanford Burnham Prebys Medical Discovery Institute today announced that Andrew Viterbi, a visionary communications pioneer and co-founder of Qualcomm Inc., has made a $5 million gift to endow the Andrew and Erna Viterbi Distinguished Chair in the Center for Data Science and Artificial Intelligence at Sanford Burnham Prebys. Continue Reading Andrew Viterbi The Center for Data Science and Artificial Intelligence brings together experts in AI, statistics, genetics and more to probe raw or untapped data to uncover patterns and insights that can inform scientists and clinicians, sparking innovation and scientific breakthroughs for new possibilities for human health. The center recently introduced an advanced computational biology tool that automates and standardizes genome sequencing analysis, enabling scientists to decipher the entire genomes of many patient samples, animal models or cultured cells in a single experiment. "I hold deep confidence in the strength of the leadership at Sanford Burnham Prebys to steward this investment with vision and purpose," said Andrew Viterbi. "Biomedical research and collaboration generate momentum used to advance computing and artificial intelligence. It's my hope that this gift will enable the Center for Data Science and AI to empower leading minds to create the breakthroughs that will advance human health." The inaugural holder of the chair will be Yuk-Lap (Kevin) Yip, PhD, director of the Center for Data Science and Artificial Intelligence, and a globally recognized leader in computational biology and bioinformatics. Dr. Yip's pioneering work harnesses advanced analytics and machine learning to uncover insights from complex biological data, accelerating progress in disease research and precision medicine. This investment by Dr. Viterbi, a distinguished philanthropist whose generosity has advanced engineering, higher education, medical research and the arts, reflects his enduring commitment to innovation and discovery, and his belief in the power of interdisciplinary science to address some of the most complex challenges in human health. Dr. Viterbi's gift will further strengthen Sanford Burnham Prebys' leadership in biomedical research powered by artificial intelligence. Viterbi is no stranger to innovation or to pushing technological boundaries. He is a co-founder and retired vice chairman and chief technical officer of Qualcomm Inc., and renowned for inventing the "Viterbi Algorithm," a dynamic programming method that finds the most likely sequence of hidden events that would explain a sequence of observed events. "Andrew has been a force, pairing extraordinary intellect with a deep commitment to advancing human knowledge and possibility," said David Brenner, MD, president and CEO of Sanford Burnham Prebys. "With this remarkable gift, he is investing in the bold vision of our Center for Data Science and AI where world-class scientists are redefining how we understand biology and disease. Together, we are unlocking the power of artificial intelligence to drive discoveries at a scale and speed once unimaginable, and to shape the future of medicine for generations to come." Through this endowed chair, Sanford Burnham Prebys will continue to attract and support world-class scientific talent, advancing breakthrough discoveries at the intersection of data science, artificial intelligence and human health poised to redefine the future of medicine. About Sanford Burnham Prebys: Celebrating its 50th anniversary, Sanford Burnham Prebys Medical Discovery Institute is an independent nonprofit biomedical research institute dedicated to understanding the fundamental biology of human health and disease and translating discoveries into advances that improve lives. Sanford Burnham Prebys has four disease-focused centers: NCI-designated Cancer Center; Center for Cardiovascular and Muscular Diseases; Center for Neurologic Diseases; and Center for Metabolic and Liver Diseases; as well as two enabling technology centers: Center for Data Science and Artificial Intelligence and Center for Therapeutics Discovery. The Institute's scientists have driven breakthroughs across cancer, neuroscience and aging, as well as diseases of the heart, muscle, metabolism and liver. Our research is strengthened by drug discovery capabilities, data science and artificial intelligence and global collaborations that help move discoveries toward real-world impact. A strong culture of collaboration, paired with a commitment to education through our graduate school to train the next generation of scientists, brings together researchers, partners and philanthropists in a shared mission to advance biomedical science and improve human health. Learn more at sbpdiscovery.org. SOURCE Sanford Burnham Prebys Medical Discovery Institute 21% more press release views with Request a Demo

Sanford Burnham Prebys Medical Discovery Institute has received a USD 3.86 million UG3 cooperative agreement from the National Institute of Neurological Disorders and Stroke to advance a non-opioid small molecule program targeting the neurotensin receptor 1 (NTR1) for pain management. The award, issued under the NIH HEAL Initiative funding opportunity RFA-NS-24-019, covers the period from April 2026 through March 2028 and lists Lauren M. Slosky, Steven H. Olson, and Ru-Rong Ji as principal investigators. The program centers on SBI-553, a beta-arrestin 2-biased allosteric modulator of NTR1 that binds at an intracellular site and selectively directs receptor signaling toward the beta-arrestin 2 pathway rather than G protein activation. Preclinical data in rodent models showed the compound reduced hypersensitivity in postoperative and neuropathic pain settings and suppressed excitatory synaptic transmission in spinal cord nociceptive neurons, with activity also observed in human nociceptive sensory neurons in vitro. The UG3 phase will use structure-based drug design and AI-assisted computational methods alongside cryo-EM co-structure determination to drive lead optimization from SBI-553 analogs toward a clinical candidate. The UG3 mechanism is milestone-contingent, with a prospective UH3 phase intended to complete IND-enabling studies and initiate a Phase I single ascending dose study in healthy volunteers, though transition to that stage remains dependent on meeting predefined criteria. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website