Page 4 – Sanford Burnham Prebys
Institute News

Science in Pictures

AuthorScott LaFee
Date

November 4, 2024

A chromosome from Drosophila melanogaster (fruit fly) salivary glands, using Brightfield microscopy. Fruit flies are model organisms, sharing 75% of the genes that cause disease in humans.

Image courtesy of Earl Nishiguchi, Kauai Community College and Nikon Small World.

Institute News

Raising awareness of breast cancer research at Sanford Burnham Prebys

AuthorGreg Calhoun
Date

October 31, 2024

The October Science Connect Series event was themed around Breast Cancer Awareness Month and featured two cancer research experts.

The Sanford Burnham Prebys Wellness Ambassadors hosted a Science Connect event on Wednesday, October 30, 2024, featuring two faculty experts discussing their breast cancer research and its implications.

The Science Connect Series provides a forum for Sanford Burnham Prebys principal investigators to share their research with administrative personnel. Faculty members gain experience in communicating their science to a lay audience, and administrators gain a better understanding of research conducted at the institute so they can become better advocates and ambassadors of the shared mission to translate science into health.

Kelly Kersten, PhD, an assistant professor in the Cancer Metabolism and Microenvironment Program, opened the event by focusing on the importance of finding new treatments —such as immunotherapies — for the one-third of breast cancer patients that are diagnosed after the early stages of the disease when surgery is less effective.

The immune system is one of the main defenses of the human body to fend off harmful pathogens and invasive cells, such as cancer. Among all white blood cells, a particular cell type, called a T cell, can directly kill cancer cells and therefore plays an essential role in building anti-tumor immune responses.

Many types of cancer are confronted and infiltrated by T cells, only to be suppressed by the local tumor environment.

“While immunotherapies that boost the immune system have revolutionized the way we treat cancer, many patients do not respond to the treatments, and the mechanisms of resistance remain largely unclear,” said Kersten.

Kersten’s goal is to understand why T cells enter a state known as exhaustion and lose their tumor-killing capacity. This knowledge will help her team find potential future therapies that could prevent T-cell exhaustion and improve immunotherapies for cancer patients.

Kevin Tharp, PhD, also an assistant professor in the Cancer Metabolism and Microenvironment Program, shared that his lab’s focus is on how cancer cells adapt their metabolism to generate the energy needed to spread to other tissues through metastasis. He presented his team’s work with the Kersten lab on another aspect of potential resistance to immunotherapy in breast cancer.

Tharp and Kersten are studying the hypothesis that part of the reason why these therapies fail is due to tumor-associated fibrosis, the creation of a thick layer of fibrous collagen (like scar tissue) that acts as a barrier against the anti-tumor immune response. They published a paper on June 3, 2024, in Nature Cancer,  discussing how tumor-associated macrophages, a type of immune cell found abundantly in the tumor microenvironment, respond to the physical properties of fibrosis.

By synthesizing injury-associated collagens that facilitate wound closure, TAMs experience metabolic changes and generate metabolic byproducts that suppress the anti-tumor function of immune cells.

“The metabolic changes in the microenvironment present more of a challenge to anti-tumor responses than the physical barrier,” said Tharp. “Our study provides an alternative explanation for why anti-tumor immunity is impaired in fibrotic solid tumors.”

To follow up on these results, Tharp is collaborating with Sarah Blair, MD, a professor of surgery at the University of California San Diego, to fund and initiate a clinical trial testing the potential of dietary supplements to counteract the suppressive effects of TAM metabolic byproducts as an adjunct therapy to surgery.

Institute News

Jamey Marth interviewed by The Scientist

AuthorGreg Calhoun
Date

October 31, 2024

The Sanford Burnham Prebys scientist discussed the Cre-loxP recombination system, which continues to be a mainstay genetic engineering technology.

“Techniques come and go with new technology, it’s just like night and day.” said Jamey Marth, PhD, professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys during his interview with The Scientist regarding his lab’s contributions to a genetic engineering technique that has stood the test of time.

“So, when you have a technique that’s lasted 30 years with no replacement technology, I think that’s kind of remarkable.”

Marth was interviewed about the Cre-loxP recombination system, which acts as a molecular genetic editor for controlling mutations in the genome. It was initially investigated by Drs. Nat Sternberg and Brian Sauer in the 1980s in tests to manipulate the genes of yeast and mammalian cells.

Marth wanted to use the technique for conditional mutagenesis in animal studies that would enable temporal and cell-type specific genetic models to better investigate biological systems and more effectively model human diseases. He and his team advanced the Cre-loxP system for use in laboratory mice and demonstrated the ability to efficiently delete DNA sequences in specific T cells in 1992.

The Cre-loxP recombination system continues to be a mainstay technology today and some scientists are exploring ways to combine it with the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease, Cas9, to gain the advantages of both genetic engineering techniques.

Institute News

Body of Art

AuthorScott LaFee
Date

October 31, 2024

Bioblasts

Richard Altmann (1852-1900) was a German prosecutor-turned-anatomy professor who focused on advancing microscopy techniques in his day. Using a new staining technique, he observed filaments in nearly every cell type he viewed. These filaments developed from granules, which Altmann deduced were elementary living units.

He called them “bioblasts.”

His conclusions were not well-received by peers.

These days, it’s believed Altmann was describing mitochondria, a term coined by Carl Benda in 1898 replaced Altmann’s “bioblasts.” And no one disputes the significance of Altmann’s original observations.

Mitochondria  are cellular organelles that covert fuel into energy, the so-called “powerhouses of the cell.” They have many responsibilities and notably, possess their own genes apart from the cell’s nucleus. This fact supports the hypothesis that mitochondria were originally free-living prokaryotic cells lacking a nucleus that permanently fused with eukaryotic cells in the distant past.

Given their fundamental and expansive importance, mitochondria are the focus of much research. At Sanford Burnham Prebys, Peter Adams, PhD, with collaborators elsewhere, are  exploring the role they play in cellular aging and immune responses, and particularly how they may affect the connection between aging and liver cancer.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Institute News

Science in Pictures

AuthorScott LaFee
Date

October 28, 2024

A colorized scanning electron micrograph of a human brain cancer stem cell. Cell bodies are  in orange; nuclei in green. Cancer stem cells possess characteristics of normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. That makes them a particularly enticing target for developing cancer therapies, especially those prone to metastasis or recurrence.

Image courtesy of Izzat Suffian, Pedro Costa, Stephen Pollard, David McCarthy & Khuloud T. Al-Jamal.

Institute News

A Conversation About Aging and Cancer at Sanford Burnham Prebys 

AuthorGreg Calhoun
Date

October 24, 2024

Event recording now available for panel discussion with scientists held on October 9, 2024

David A. Brenner, MD, president and CEO of Sanford Burnham Prebys, welcomed attendees to the launch of a new community engagement program called “A Conversation About” in the institute’s Victor E. LaFave III Memorial Auditorium on October 9, 2024.

The initial panel discussion in the A Conversation About series focused on the connection between aging and cancer and included information about a current breast cancer research collaboration. A recording of the event is available online.

Reena Horowitz, the founder of Group of 12 and Friends at Sanford Burnham Prebys, provided introductory remarks. Brooke Emerling, PhD, director of the Cancer Metabolism and Microenvironment Program, moderated the discussion among three featured panelists:

  • Peter Adams, PhD, director of the Cancer Genome and Epigenetics Program, Sanford Burnham Prebys
  • Xiao Tian, PhD, assistant professor in the Degenerative Diseases Program, Sanford Burnham Prebys
  • Kay Yeung, MD, PhD, associate clinical professor in the Division of Hematology-Oncology, University of California San Diego Health

By bringing together community collaborators and clinicians with Sanford Burnham Prebys researchers, A Conversation About offers a unique perspective on how clinical research and practice can be used to inform fundamental and translational science.

Watch Event Recording

Institute News

Body of Art

AuthorScott LaFee
Date

October 24, 2024

T cell killing cancer cell

T cells are a type of white blood cell (lymphocytes) that develop from stem cells in bone marrow and are part of the adaptive immune system, which constantly monitors the body for threats. They help protect the body from infection and may help fight cancer. Each T cell is unique, designed to fight only one type of intruder.

 At Sanford Burnham Prebys, Linda Bradley, PhD, Jennifer Hope, PhD, and colleagues are working to help revive exhausted T cells to tackle immunotherapy-resistant cancers—a major emphasis in cancer research.

Meanwhile, Kelly Kersten, PhD, is studying how T cells fundamentally interact with cancer cells and the microenvironment, looking for ways to improve immunotherapies and reduce the likelihood of treatment resistance, which is common in many types of cancer.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Institute News

Science in Pictures

AuthorScott LaFee
Date

October 21, 2024

A colorized scanning electron micrograph of a natural killer cell from a human donor. NK cells are a type of white blood cell critical to the innate immune system. They  provide rapid responses to virus-infected cells, stressed cells, tumor cells and other intracellular pathogens based on signals from several activating and inhibitory receptors.

Image courtesy NIAID.

Institute News

Two Sanford Burnham Prebys scientists selected for American Cancer Society postdoctoral fellowships

AuthorGreg Calhoun
Date

October 18, 2024

Funds will support Alicia Llorente Lope and Ambroise Manceau who study breast and pancreatic cancer

Alicia Llorente Lope, PhD, and Ambroise Manceau, PhD, were awarded 2024 Postdoctoral Fellowships from the American Cancer Society (ACS). These prestigious awards provide more than $65,000 per year for up to three years to support early career scientists studying cancer.

“I was so excited when I heard the news,” said Llorente. “It is a privilege to have this award, and it feels very validating to know that someone saw enough potential in my research to deem it worthy of funding.”

Tackling treatment-resistant breast cancer

Llorente joined the lab of Brooke Emerling, PhD, director of the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys, nearly three years ago after beginning her breast cancer research career as a doctoral student.

“I was first interested in breast cancer because my grandmother died of the disease, and I wanted to contribute to finding new therapeutic opportunities for cancer patients,” said Llorente. Llorente’s ACS-funded research project focuses on HER2-positive (HER2+) breast cancer.

Roughly one in five breast cancer tumors have elevated levels of the HER2 protein. While these tumors tend to grow quickly, drugs targeting the HER2 protein are usually effective at first. However, HER2+ tumors often are able to adapt and develop resistance to these drugs over time, leaving patients with few if any remaining treatments options.

Llorente has found evidence that a form of the protein phosphatidylinositol-5-phosphate 4-kinase (PI5P4K) plays a role in breast cancer tumors becoming resistant to HER2 drugs.

Brooke Emerling

Brooke Emerling, PhD

“We’ve revealed a strong connection between elevated levels of PI5P4K gamma and reduced survival rates in patients with HER2+ breast cancer,” explained Llorente. “I plan to explore whether targeting both HER2 and PI5P4K gamma in breast cancer cells may provide a path to overcoming treatment resistance.” Llorente also will study the functions of PI5P4K gamma in breast cancer cells to see why these cells cease to respond to HER2-targeting drugs.

“I am incredibly proud of Alicia for spearheading this groundbreaking project targeting the lipid kinase PI5P4K gamma,” said Emerling. “Her insightful analysis of breast cancer datasets, which uncovered a correlation between elevated expression of PI5P4K gamma and worse outcomes in HER2+ patients, has set the stage for vital research aimed at overcoming the significant challenge of resistance to targeted therapies in HER2+ tumors.”

Cosimo Commisso headshot

Cosimo Commisso, PhD

Powering down pancreatic cancer

Manceau is in the second year of his postdoctoral training in the lab of Cosimo Commisso, PhD, interim director and deputy director of the institute’s NCI-Designated Cancer Center. During his doctoral program, Manceau studied how abnormal cells die in a programmed series of steps called apoptosis, a process known to go awry in cancer and neurodegenerative diseases.

“It began as a basic science project about the molecular processes around cell death, and over time it led to possible therapeutic implications,” said Manceau. “I learned that I like to study fundamental biology and then try to find an application for it, and I saw in the Commisso lab an opportunity to do just that in pancreatic cancer.”

Manceau’s fellowship project focuses on pancreatic ductal adenocarcinoma (PDAC) — the most common form of pancreatic cancer with only a 13% five-year survival rate — and its ravenous pursuit of energy. Because of PDAC cells’ constant need for fuel to sustain their rampant growth, they adapt by reshaping the surface of their cells to snatch extra nutrients from the jelly-like substance between cells.

Commisso and others have shown that cutting off the extra power supplied by this process — known as macropinocytosis — reduces tumor growth. Manceau has studied the contents taken by contorted pancreatic cell surfaces in pockets called macropinosomes. By analyzing every single protein in this scooped goop, he found that calcium transporter proteins present in macropinosomes also are required for macropinocytosis.

“During the fellowship, I will work to understand how these transporter proteins affect macropinocytosis,” said Manceau. “These proteins have never been targeted before in pancreatic cancer, so our long-term goal is to use this strategy to cut the nutrient supply to tumors and see if we can inhibit tumor growth.”

“By disrupting the cancer cells’ ability to feed themselves through macropinocytosis, we can potentially starve tumors and inhibit their growth,” added Commisso. “Ambroise’s research aims to target key proteins involved in this process, opening up new possibilities for treatments that could significantly improve outcomes for patients battling pancreatic cancer.”

Institute News

Body of Art

AuthorScott LaFee
Date

October 17, 2024

Cardiac muscle

Despite decades of research, heart disease is still the leading cause of death in the industrialized world. The human heart beats roughly 100,000 times a day pushing 2,000 gallons, or about five quarts a minute. Disorders that affect the abilities of cardiac muscle to beat normally are called cardiomyopathies. They can affect people of any age, race or sex, and are often inherited. Cardiomyopathy poses a significant health risk, leading to heart failure. More than half of all heart transplants are due to cardiomyopathies.

Among the most common of cardiomyopathies is atrial fibrillation or AFib, a form of cardiac arrhythmia in which the heart beats abnormally: usually too fast and irregularly. More than 5 million people in the U.S. have AFib, which in 2021 was cited in 232,030 death certificates and named as the underlying cause of death in 28,037. The risk of developing AFib is increased by congenital defects, heart attacks, high blood pressure, pneumonia, viral infections and sleep disorders. The biggest risk factor is age with roughly 10% of people over age 65 developing AFib. How genetics, age and other risk factors interact to cause AFib is unknown.

At Sanford Burnham Prebys, researchers are investigating the gene networks that result in AFib. Recently, Alexandre Colas, PhD, and Karen Ocorr, PhD, with colleagues elsewhere, published findings that describe a multi-model platform for identifying causative genes for AFib, a major step toward finding new treatments.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.