American Cancer Society (ACS) Archives - Sanford Burnham Prebys

Tag: American Cancer Society (ACS)

Institute News

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

AuthorGreg Calhoun
Date

October 18, 2024

combined photos of Alicia Llorente Lope and Ambroise Manteau
Alicia Llorente Lope, PhD, is a postdoctoral associate in the lab of Brooke Emerling, PhD, director of the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys. Ambroise Manceau, PhD, is a postdoctoral associate in the lab of Cosimo Commisso, PhD, interim director and deputy director of the institute’s NCI-Designated Cancer Center.

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

How a protein component of nuclear pore complexes regulates development of blood cells and may contribute to myeloid disorders

AuthorCommunications
Date

June 5, 2024

A computer graphic depicts a nuclear pore in a eukaryotic cell. Nuclear pores are large protein complexes that span the nuclear membrane and allow the movement of molecules, such as proteins, RNAs, and other molecules between the nucleus and the cell’s cytoplasm. Image courtesy of M. Towler and J. Aitken, Wellcome Collection.
Computer graphic depicts a nuclear pore in a eukaryotic cell. Nuclear pores are large protein complexes that span the nuclear membrane & allow the movement of molecules, such as proteins, RNAs, & other molecules between the nucleus & the cell’s cytoplasm.

Nuclear pore complexes (NPCs) are channels composed of multiple proteins that ferry molecules in and out of the nucleus, regulating many critical cellular functions, such as gene expression, chromatin organization and RNA processes that influence cell survival, proliferation, and differentiation.

In recent years, new studies, including work by Maximiliano D’Angelo, PhD, associate professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys, have noted that NPCs in cancer cells are different, but how these alterations contribute to malignancy and tumor development—or even how NPCs function in normal cells—is poorly understood.

In a new paper, published June 5, 2024 in Science Advances, D’Angelo with first author Valeria Guglielmi, PhD, and co-author Davina Lam, uncover Nup358, one of roughly 30 proteins that form the NPCs, as an early player in the development of myeloid cells, blood cells that if not formed or working properly leads to myeloid disorders such as leukemias.

The researchers found that when they eliminated Nup358 in a mouse model, the animals experienced a severe loss of mature myeloid cells, a group of critical immune cells responsible for fighting pathogens that are also responsible for several human diseases including cancer. Notably, Nup358 deficient mice showed an abnormal accumulation of early progenitors of myeloid cells referred as myeloid-primed multipotent progenitors (MPPs).

“MPPs are one of the earliest precursors of blood cells,” said D’Angelo. “They are produced in the bone marrow from hematopoietic stem cells, and they differentiate to generate the different types of blood cells.

Maximiliano D’Angelo and Valeria Guglielmi

“There are different populations of MPPs that are responsible for producing specific blood cells and we found that in the absence of Nup358, the MPPs that generate myeloid cells, which include red blood cells and key components of the immune system, get stuck in the differentiation process.”

Fundamentally, said Gugliemi, Nup358 has a critical function in the early stages of myelopoiesis (the production of myeloid cells). “This is a very important finding because it provides insights into how blood cells develop, and can help to establish how alterations in Nup358 contribute to blood malignancies.”

The findings fit into D’Angelo’s ongoing research to elucidate the critical responsibilities of NPCs in healthy cells and how alterations to them contribute to immune dysfunction and the development and progression of cancer.

“Our long-term goal is to develop novel therapies targeting transport machinery like NPCs,” said D’Angelo, who recently received a two-year, $300,000 Discovery Grant from the American Cancer Society to advance his work.

This research was supported in part by a Research Scholar Grant from the American Cancer Society (RSG-17-148-01), the Department of Defense (grant W81XWH-20-1-0212) and the National Institutes of Health (AI148668).

The study’s DOI is 10.1126/sciadv.adn8963.

Institute News

Sanford Burnham Prebys scientists win two American Cancer Society awards

AuthorMonica May
Date

October 1, 2019

Robert Wechsler-Reya, PhD, Jorge Moscat, PhD, and Maria Diaz-Meco, PhD

Innovation and Collaboration of the Year Awards

The San Diego cancer community—including oncologists, oncology nurses, radiologists, cancer researchers and their friends and family—gathered on September 22 to celebrate progress made in reducing cancer deaths and recognize exceptional individuals and institutions at the inaugural American Cancer Society’s Celebration of Cancer Care Champions in San Diego.

More than 40 finalists were selected, including Sanford Burnham Prebys professors Robert Wechsler-Reya, PhD, who received the Innovation of the Year award for his team’s creation of a new model for studying a brain tumor that commonly arises in infants; and Jorge Moscat, PhD, and Maria Diaz-Meco, PhD, who received the Collaboration of the Year award for their partnership with clinicians at Scripps Clinic who uncovered a novel way to potentially identify a deadly form of colorectal cancer.

Nominations were reviewed by an independent review committee composed of representatives from 10 leading healthcare and research institutions, including Celgene, Kaiser Permanente, Rady Children’s Hospital, Scripps MD Anderson Cancer Center, Moores Cancer Center at UC San Diego Health and more. (Note: Members of the review committee did not score nominations for their own institutions.)

Read on to learn more about our award-winning research:

Innovation of the Year: A new model for studying brain tumors that strike infants
Robert Wechsler-Reya, PhD, a professor at Sanford Burnham Prebys and program director of the Joseph Clayes III Research Center for Neuro-Oncology and Genomics at the Rady Children’s Institute for Genomic Medicine, was honored for his development of a novel mouse model of a pediatric brain tumor called choroid plexus carcinoma. This tumor most commonly arises in infants under the age of one who are too young to undergo radiation treatment. Until now, drug development has been hindered by the lack of models that could help researchers better understand the cancer. Wechsler-Reya and his team have already used the model to identify potential drug compounds that may be therapeutically useful.

Collaboration of the Year (tie): Novel biomarkers to help detect a deadly colorectal cancer 
Sanford Burnham Prebys professors Jorge Moscat, PhD, and Maria Diaz-Meco, PhD; and Scripps Clinic clinicians Darren Sigal, MD, and Fei Baio, MD, were recognized for their successful collaboration. Together, the researchers revealed that loss of two genes drives the formation of the deadly serrated form of colorectal cancer—yielding promising biomarkers that could identify the tumor type. This insight could lead to the development of a diagnostic test to identify serrated colorectal cancer, a hurdle that previously limited our understanding of this deadly cancer type and the development of effective treatments. The research also identified a combination treatment that has treated the cancer in mice.