Siteman Catalyst Awards Support Groundbreaking Science

Four researchers receive new funding to explore brain‑sparing radiation, smarter leukemia drugs, better BRCA1 risk prediction and new strategies against aggressive pancreatic cancer

Four WashU Medicine researchers at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, have received Siteman Catalyst Awards to pursue innovative ideas that could change how cancers are detected and treated.

Each awardee is receiving $100,000 for an early-stage project that is too new for traditional funding but has strong potential to benefit patients. Together, these efforts aim to move promising science from the lab toward real advances in cancer care.

The researchers are:

• Adam Bauer, PhD, associate professor of radiology and of biomedical engineering, who aims to better protect memory and cognitive ability in people who need whole-brain radiation.
• Alireza Ghanbarpour, PhD, associate professor of biochemistry and molecular biophysics, who is researching a new weak point in leukemia cells’ energy machinery, which could lead to new therapies.
• Priyanka Verma, PhD, associate professor of medicine, who seeks to improve how doctors interpret BRCA1 gene changes that affect breast cancer risk, information that could sooner mitigate the chances of breast cancer development.
• Max Wattenberg, MD, associate professor of medicine, who is studying new ways to treat pancreatic cancer that has spread to the lining of the abdomen.

Please see below for more details on each project.

Reducing Radiation Induced Cognitive Decline Through Inhibiting Neuroinflammation

Principal Investigator: Adam Bauer, PhD

Goal: To determine whether a drug called azeliragon can help protect memory and thinking after whole-brain radiation treatment

Summary: Many brain tumor survivors experience progressive and disabling cognitive decline within months of radiotherapy, leading to impairment and reduced quality of life. The underlying mechanisms are not fully understood, and there are currently no strategies to accurately predict, monitor or prevent this decline. This project will leverage novel optical neuroimaging to establish how radiotherapy and neuroinflammation separately influence brain activity in mice to determine early biomarkers of radiation-induced cognitive decline. Researchers will also determine whether inhibiting radiation-induced neuroinflammation using a novel drug prevents cognitive decline and corresponding changes to neuroimaging biomarkers. Their long-term goals are to develop neuroimaging-based biomarkers to predict cognitive decline in brain tumor survivors after radiotherapy and to develop novel, preventative treatments for brain tumor patients.

Elucidating the Molecular Mechanisms of Mitochondrial Protein Degradation in Cancer

Principal Investigator: Alireza Ghanbarpour, PhD

Goal: To understand how a special protein called ClpXP supports survival in leukemia cells. By better understanding how this process works, researchers will have the knowledge to guide the development of new cancer therapies for leukemia

Summary: Cancer cells require large amounts of energy to grow and divide rapidly. To meet this demand, they rely heavily on mitochondria, the structures in cells that produce energy. Because mitochondria in cancer cells operate under high stress, they depend on systems that remove damaged proteins and maintain mitochondrial function. One such system is ClpXP, a molecular machine that keeps mitochondria healthy by identifying and destroying damaged or unnecessary proteins. Cancer cells appear to depend on ClpXP more than normal cells, meaning that blocking its activity could selectively harm cancer cells while causing fewer side effects in healthy cells. This project will identify the mitochondrial proteins controlled by ClpXP and determine how this system recognizes and destroys its targets, which may help guide the development of new cancer therapies.

Defining the Pathogenicity of BRCA1 Germline Mutations in Predisposition to Breast Cancers

Principal Investigator: Priyanka Verma, PhD

Goal: To develop a platform to predict breast cancer preposition risk in individuals with mutations in the BRCA1 gene

Summary: This project aims to develop ways by which an individual’s genetic information can be used to predict if they are more susceptible to developing breast cancers as compared to general population. Having this information in a timely manner can be used to undertake available preventive measures to mitigate the chances of breast cancer development.

Investigating Peritoneal Anti-Metastatic Programs in Pancreatic Cancer

Principal Investigator: Max Wattenberg, MD

Goal: To understand how the immune system interacts with pancreatic cancer cells in the peritoneum (the lining of the abdomen) and find new ways to treat cancer that spreads to these sites

Summary: Pancreatic cancer often spreads to the peritoneum, the lining of the belly, causing serious health problems such as pain, bowel obstruction and fluid buildup. These sites of cancer spread are hard to treat because they resist current drugs, and there are no effective treatments specifically for them. This project uses studies with mice and patient samples to examine how pancreatic cancer cells and the body’s immune system interact in the peritoneum. By understanding these interactions, researchers hope to develop new treatments to help the immune system better fight pancreatic cancer.