DISCOVERIES

January 2025

Scientists show how the advanced form of fatty liver disease has effects on liver cancer risk

Liver cancer has proven to be a tough beast to tame. Experts expected rates of the cancer to decrease following the development of the hepatitis B vaccine in the 1980s, which reduced one of the major risk factors for the disease.

Research in Taiwan showed that its universal infant hepatitis B vaccination program led to young adults experiencing a 35.9% reduction in cases of hepatocellular carcinoma (HCC), the most common liver cancer.

Despite innovation leading to the world’s first cancer-preventing vaccine, incidence of HCC has been on the rise due to a spike in fatty liver disease over recent decades. Lifestyle factors such as high-calorie diets, excessive alcohol consumption and minimal exercise — along with genetic predispositions—can lead to problematic changes in the liver, heart and kidneys.

In a paper published January 1, 2025, in Nature, scientists at Sanford Burnham Prebys, the University of California San Diego, Curtin University, the University of Pennsylvania and the Liver Cancer Collaborative, demonstrated that a condition known as metabolic-associated steatohepatitis (MASH) damages the DNA of liver cells. The study also linked these changes to the development of liver cancer.

Bile may be key to immunotherapy effectiveness in liver cancer

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and a growing threat to public health across the globe due to the rising rate of fatty liver disease.

Liver cancer is difficult to treat as it often causes few, if any, symptoms early on, so it tends to be diagnosed at later, more aggressive stages. While immunotherapies that supercharge patients’ immune systems have proven effective in some cancers, this approach has had limited success in patients with HCC or other forms of the disease.

Scientists are investigating the unique qualities of different tissues that may explain why the effectiveness of immunotherapy varies depending on the location of a tumor. The liver is known to have a flexible immune system capable of defending itself when necessary while not overreacting to a constant flood of foreign materials from digesting food, including metabolic byproducts from bacteria residing in the gut microbiome.

In a paper published January 9, 2025, in Science, scientists from Sanford Burnham Prebys, the Salk Institute, the University of California San Diego, Columbia University Irving Medical Center, Memorial Sloan Kettering Cancer Center and the Geisel School of Medicine at Dartmouth, found that a critical ingredient in bile hinders the liver’s immune response against cancer.

Common gut bacteria have a taste for tungsten

In a paper published December 30, 2024, in PNAS, study coauthor Dmitry A. Rodionov, PhD, research assistant professor in the Immunity and Pathogenesis Program at Sanford Burnham Prebys, and colleagues, studied how Eubacterium limosum contributes to a healthy human gastrointestinal microbiome by metabolizing lactate.

Lactate or lactic acid is a normal byproduct that is created as our cells generate energy. Lactate can be found in the guts of healthy adults at low concentrations because microbes such as E. limosum make a meal of much of it, preventing the abnormal accumulation sometimes found in patients with ulcerative colitis and other gut-related disorders.

Mutations in protein receptor gene linked to Alzheimer’s disease

Upon inspecting the DNA sequences in patients with Alzheimer’s disease, scientists have found evidence of an inconspicuous conspirator.

The EPHA1 gene contains the blueprint for the EPHA1 receptor protein, one of 14 such receptor proteins in the Eph receptor family. Relatively little is known about EPHA1 when compared to many of its siblings, making it difficult for researchers to ascertain why changes in its source code would contribute to such a debilitating disease.

Elena Pasquale, PhD, and other scientists from Sanford Burnham Prebys published results on December 18, 2024, in the Journal of Biological Chemistry, detailing the effects of four miniature mutations of just a single typo each in the sequence of nucleotides forming the EPHA1 gene.

Philanthropy

Make a big impact with a future gift

Generosity comes in many forms, and it’s often the best way for you to support important causes that matter the most to you. When you give to Sanford Burnham Prebys, you help us make a difference. We will work with you to find a charitable plan that is best for you and your family while providing vital support to our mission.

If you let us know about your intended bequest or other planned gift, we will be able to thank you and recognize you as a member of our Legacy Circle, which honors those who have made a planned gift to Sanford Burnham Prebys.

For more information, please contact Sandy Liarakos, Vice President of Philanthropy at sliarakos@sbpdiscovery.org

Learn more about our Legacy Circle >>

Community

Valeria Guglielmi, PhD, awarded grant to further investigate genetic condition that results in soft, deformed bones and lost teeth

Soft Bones, an advocacy group for HPP patients, recently awarded Valeria Guglielmi, PhD, a postdoctoral associate in Maximiliano D’Angelo’s lab, a one-year, $25,000 seed grant to further investigate the involvement of tissue-nonspecific alkaline phosphatase (TNAP) in inflammatory responses and immune cell functions.

Hypophosphatasia (HPP) is a rare genetic disorder in which bones and teeth fail to take up sufficient calcium and phosphorus needed to achieve proper hardness and strength. Defective mineralization results in bones that are soft and prone to fracture and deformity, and the loss of teeth. Occasionally, HPP can cause death due to complications.

Prevalence varies by severity and age of onset. It is rarest but most severe at birth (1 in 100,000 live births), with lower prevalence and milder forms in later years. The condition can manifest at any age.

The cause of HPP is a mutation in an enzyme called TNAP, which plays a critical role in skeletal and dental mineralization. In 2015, an enzyme replacement therapy developed by José Luis Millán, PhD, a professor in the Human Genetics Program at Sanford Burnham Prebys, was approved to treat pediatric onset HPP, dramatically improving patients’ lifespan and quality of life.

However the effects of TNAP deficiency appear to extend beyond faulty mineralization. HPP patients also experience altered immune responses, suggesting TNAP might have a role in immune cells.

Leona M. Flores, PhD, named vice president of research operations at Sanford Burnham Prebys

Leona M. Flores, PhD, has been named vice president of research operations at Sanford Burnham Prebys. She will elevate the research capacity of the Institute by working with faculty and other scientists to ensure successful execution of research projects and reducing the increasingly complex administrative burden of research.

She officially joined Sanford Burnham Prebys on January 6, 2025.

“I was drawn to Sanford Burnham Prebys because of the compelling vision Dr. Brenner has set forth for strengthening our research enterprise,” said Flores. “I’m excited by the opportunity to work alongside dedicated and talented colleagues in advancing this vital mission.”

Flores will oversee a team responsible for advancing the Institute’s mission by providing professional project management techniques, administrative support and research resources to Sanford Burnham Prebys laboratories. Her initial focus will be ensuring the successful renewal of the Institute’s National Cancer Institute-designated Cancer Center, now in its 43rd year.

AI-driven cancer prediction tool makes NIH director’s highlights for 2024

On April 18, 2024, first author Sanju Sinha, PhD, an assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys, and colleagues published details about a new artificial intelligence-powered tool called PERCEPTION (PERsonalized Single-Cell Expression-Based Planning for Treatments In ONcology).

PERCEPTION was proof-of-concept that AI could be used to predict a cancer’s treatment responses from bulk RNA. Sinha and colleagues built AI models for 44 drugs approved by the FDA and found that their tool “predicted the success of targeted treatments against cell lines with a high degree of accuracy.”

The paper was one of six specifically highlighted by Monica Bertagnolli, MD, in her blog post “2024 Science Highlights” as director of the National Institutes of Health.

Hudson Freeze finds life in hot water

Hudson Freeze, PhD, director and professor of the Human Genetics Program, has a starring cameo in Veritasium’s video profile of Kary Mullis, PhD.

Kary Mullis, PhD, (1944-2019), was an American biochemist who shared the 1993 Nobel Prize in Chemistry for his role in the invention of polymerase chain reaction (PCR), which fundamentally altered biochemistry, the study of DNA and helped lead to the new field of biotechnology.

Freeze, then an undergraduate student in the lab of Indiana University microbiologist Thomas D. Brock, PhD, (1926-2021), discovered a new species of bacteria able to live in 160ºF. hot springs at Yellowstone National Park. Conventional wisdom at the time said no life could survive such temperatures.

View video >>

In the News

hands reaching for GLP-1 drug pen injector

Opinion: On weight loss drugs, here’s what you need to know before trying them

In his latest essay for The San Diego Union-Tribune and elsewhere, David Brenner, MD, president and chief-executive-officer of Sanford Burnham Prebys, discusses the weighty topic of GLP-1 drugs, their pros and cons, gains and losses.

Science in Pictures

A healthy arteriole in eye, with tough, flexible elastin wall (pink), red blood cells (red) and supporting collagen fibers (web-like netting) surrounded by yellow and green areas.

Image courtesy of Donald Pottle, The Schepens Eye Research Institute, Boston and Bioscapes.