DISCOVERIES

January 2024

A new 3D bioprinted model offers a novel tool to study common liver disease, and perhaps find an effective treatment

Metabolic dysfunctio-associated steatohepatitis or MASH (formerly known as nonalcoholic steatohepatitis) is an inflammatory, liver-scarring disease that affects 1.5% to 6.5% of all U.S. adults. There are no approved pharmacological therapies for MASH and in the most severe case, the only recourse is liver transplantation.

In a new study with collaborators at Viscient Biosciences, Salk Institute and UC San Diego, senior author David Brenner, M.D., CEO and president of Sanford Burnham Prebys, describes development of a novel three-dimensional bioprinted liver tissue model that uses liver cells from healthy or MASH-diseased donors and represents a critical new tool in both understanding the disease and finding effective treatments.

Shengjie Feng channels the powers of cryogenic electron microscopy

Shengjie Feng, Ph.D., who recently joined Sanford Burnham Prebys an assistant professor in the Degenerative Diseases program, is an expert in how to leverage the powers of cryo-EM, an imaging technology that can create stop-action movies of proteins and other biomolecules jostling and connecting with each other while mitochondria and other organelles generate energy, assemble new molecules and transport cargo.

It is biology in action, and a powerful tool for drug discovery and translational research across disciplines.

When T cells and macrophages talk, Kelly Kersten listens

Kelly Kersten, Ph.D., joined Sanford Burnham Prebys this month as an assistant professor in the Cancer Metabolism and Microenvironment program. She studies the interactions between immune cells and their microenvironment to better understand how they contribute to anti-tumor immune responses, with the goal of improving existing therapies to cure cancer.

Sanjeev Ranade wants to get to the heart of congenital disease

Sanjeev S. Ranade, Ph.D., who recently joined the faculty of Sanford Burnham Prebys as an assistant professor in the Development, Aging and Regeneration program, studies transcription factors (TFs), proteins that initiate and regulate the transcription of genes, essentially turning genes on and off, boosting or repressing their activity. At last count, there were over 1,500 known TFs. Ranade focuses on TFs that specifically control the development and function of cardiac cells—and what happens when things go wrong, leading to congenital heart defects in children.

Hudson Freeze appointed to Distinguished Endowed Chair, thanks to gift from grateful supporter

Thanks to a generous gift from Dinah C. Ruch, Hudson Freeze, Ph.D., director of the Sanford Children’s Health Research Center at Sanford Burnham Prebys, has received the William W. Ruch Distinguished Endowed Chair. The newly created chair will support Freeze’s research on congenital disorders of glycosylation (CDGs) and rare children’s diseases.

New roles for autophagy genes in cellular waste management and aging

Autophagy, which declines with age, may hold more mysteries than researchers previously suspected. In the January 4 issue of Nature Aging, it was noted that scientists from the Buck Institute, Caroline Kumsta, Ph.D. at Sanford Burnham Prebys and Rutgers University have uncovered possible novel functions for various autophagy genes, which may control different forms of disposal including misfolded proteins—and ultimately affect aging.

A potential new weapon against a deadly, drug-resistant bacterial pathogen

Carbapenems are a class of highly effective antibiotics that are often used to treat severe bacterial infections. They are usually reserved for known or suspected bacterial infections resistant to other drugs.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is, as the name suggests, impervious to carbapenems; and it has become a major global pathogen, particularly in hospital settings and conflict zones. No new antibiotic chemical class with activity against A. baumannii has successfully emerged in more than 50 years.

In a paper published January 3, 2024, in Nature, a multi-institutional team including Andrei Osterman, Ph.D., at Sanford Burnham Prebys, with colleagues at Roche—the Swiss-based pharmaceutical/healthcare company—and others, describe a novel class of small-molecule tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against CRAB. Osterman’s lab provided critical data and discoveries related to the drug target and mapping of drug-resistant mutations.

Institute research plays a key role in developing microbiome-directed complementary food to help save malnourished children

Among the consequences of childhood malnutrition is the underdevelopment of their gut microbiomes, critical to human health, from innate immunity to appetite and energy metabolism.

Although malnourished children gain some weight and grow better when fed a nutrient-rich diet, they do not catch up to their well-fed counterparts—and their gut microbiomes do not recover.

With bioinformatics support from Andrei L. Osterman, Ph.D., professor in the Immunity and Pathogenesis and Cancer Metabolism and Microenvironment programs at Sanford Burnham Prebys and his colleagues Dmitry Rodionov, Ph.D., and Alex Arzamasov, a multi-institutional scientific team has published new research that identifies and describes the bioactive elements of microbiome-directed food.

In the News

Opinion: Science is advancing past the need for drug testing on animals. Let’s embrace alternatives.

In his latest San Diego Union-Tribune essay, David Brenner talks about the need and promise of moving away from animal testing in science to rapidly developing alternatives, such as cell cultures, bioprinted organs, noninvasive imaging and computational models.