State: California

Metabolism is how cells use nutrients to make energy and build the molecules they need to live. Cancer cells, unlike healthy cells, can change these processes. This rewiring helps them grow faster, resist stress, and avoid death. Learning how this happens may lead to new treatments.Our lab uses data-driven tools to study cancer metabolism. One of our main methods is mass spectrometry. This tool measures thousands of proteins and metabolites, and these molecules are the building blocks of metabolism. By measuring them in cancer, we can create a clear picture of how cancer cells use their metabolism to their advantage. These large datasets also allow us to use machine learning to find hidden patterns and weak points that cancer depends on.With this approach, we found a protein that controls the levels of cysteine, an amino acid that cancer cells need to grow and survive. The protein works by sensing and adjusting cysteine levels in cells. We are now testing if it can be a new drug target to kill cancer cells. In the future, we will use similar methods to find more hidden rules that let tumors survive. Our goal is to turn these findings into better cancer treatments that directly target cancer’s unique metabolic needs.

Bladder cancer is the 5th most common cancer in the United States and causes about 17,000 deaths each year. When it spreads to other parts of the body, patients usually live less than two years. In the past few years, a new type of treatment called antibody drug conjugates (ADCs) has changed how bladder cancer is treated. One of these drugs, enfortumab vedotin (EV), targets a protein on bladder cancer cells called NECTIN4. When EV is used alone or with immunotherapy, this new therapy can shrink tumors in nearly 70% of patients at first. Sadly, most patients with bladder cancer become resistant after about a year, which means that the cancer stops responding to the treatment.We first thought this resistance might happen because tumors lose expression of the target NECTIN4. But when we looked at tissue samples from patients whose cancer stopped responding, we found most resistant tumors still had it. This project will explore other reasons why resistance happens and how to delay or reverse it. This includes looking at how the drug is processed inside cells, how it gets broken down, and how immune cells around the tumor may play a role. We will study both cancer cells and patient samples to see what changes occur as resistance develops. We will also test new drug designs, try other ways of targeting NECTIN4, and build new lab models from patients whose cancers are resistant. This work could lead to better treatments not only for bladder cancer but also for other cancers treated with ADCs.

Glioblastoma (GBM) is one of the most common and deadly brain cancers, and survival rates have barely improved in decades. In our research, we found a hidden weakness in GBM tumors that could lead to a new treatment. Think of p53 as the body’s security guard that protects against cancer. But in about 71% of GBM tumors, another protein called BRD8 locks up this guard so it can’t do its job. We discovered a way to break apart BRD8 with new drugs, which could free p53 and let it fight the cancer again. We will test this approach using lab-grown GBM cells and mini-brain tumor models created from patient samples. Our approach could help develop new therapeutic strategies for patients facing this devastating disease.

Funded by the Stuart Scott Memorial Cancer Research Fund

Lung cancer is the leading cause of cancer-related deaths worldwide. The most common type is called non-small cell lung cancer (NSCLC), which consists mostly of adenocarcinomas and squamous cell carcinomas. In about 15–20% of adenocarcinoma cases, the cancer is caused by changes in a gene called EGFR. This gene normally makes a protein that helps cells grow and divide in a healthy way. But when EGFR is changed, or mutated, it can send the wrong signals, causing cells to grow out of control and form cancers. There are already drugs that target some EGFR mutations. These medicines, called EGFR tyrosine kinase inhibitors, can be very effective for certain patients. However, they only work for specific mutations in one part of the EGFR protein. Other mutations, found in a different part of the protein called the extracellular domain (the section that sits outside the cell), don’t respond to any of the current treatments. These mutations are less common, but they still affect many people with lung cancer. Unfortunately, scientists know far less about them. Our project aims to change that. Using human lung cells and advanced 3D models called organoids, we are studying how these rare EGFR mutations cause cancer, how they interact with other cancer genes, and why today’s drugs don’t work. We are also using new genetic tools to search for weak spots in these cancer cells that could become targets for future medicines. By uncovering how these overlooked mutations drive cancer, we hope to open the door to better treatments for patients with lung cancer.

Funded by the Dick Vitale Pediatric Cancer Research Fund

Diffuse midline glioma is a deadly brain tumor that affects children. Radiation is the main treatment, since surgery and chemotherapy do not work well. New drugs are being tested, but they are not proven yet. To find better options, we built a new method that combines gene disruption with detailed study of brain tumors. This lets us test the role of many genes in new ways. We found genes that may help tumors respond better to treatment. Now, we will study how these genes work. Our goal is to discover new treatment combinations that can help children with glioma live longer and healthier lives.