Cancer cells are always growing, and they need nutrients to keep up this fast growth. An exciting idea is that we might be able to starve cancer cells without harming healthy cells by getting rid of nutrients that cancer cells need. A drug being developed right now called ADI-PEG20 destroys a nutrient called arginine, which is an amino acid that is used to make protein and is particularly important for cancer cells. My lab studies what happens when cancer cells don’t have enough arginine. We want to understand how ADI-PEG20 works, how to improve it, and which cancers to treat with it. We have found that restricting arginine disrupts ribosomes, the machines that build new protein, causing them to get stuck and abandon their jobs early. We want to study three things to figure out how this impacts ADI-PEG20 treatment. First, why is protein production in cancer cells so sensitive to arginine levels? Next, what machinery in the cell is responsible for causing “starved” ribosomes to press the eject button in the middle of doing their jobs? Finally, what effect does this have on a cancer cell? This work will help us understand how a nutrient like arginine can directly control very important processes in the cell like protein production. It will also reveal how we can take advantage of cancer’s dependence on arginine to shrink tumors.
Multiple myeloma and AL amyloidosis are incurable cancers of blood cells. These blood cells are called plasma cells. There is only one therapy that is available for AL amyloidosis patients. In severe stages, AL amyloidosis patients survive less than one year. Amyloidosis plasma cells cause damage to the body by spilling in the blood a sticky protein. These sticky proteins attach to each other and build up in the heart. Buildup of proteins in the heart causes progressive poor function. AL amyloidosis is a major cause of malfunctioning of the heart and death. To cure AL amyloidosis, we need drugs that 1- stop plasma cells from spilling sticky proteins; 2- kill the cancer plasma cells; and 3-remove the buildup of sticky proteins from the heart. These drugs do not exist, because we do not know how sticky proteins get spilled and why the build-up is not removed.Recently, our lab found out how sticky proteins get out of amyloidosis plasma cells. We also showed that if we stop this process, cancer cells die. Finally, we discovered that cleaner cells that should remove sticky proteins from the heart are reduced and do not function in amyloidosis patients. Based on these data, we will make two novel drugs. One will stop spillage of sticky proteins and kill cancer cells. The other will remove sticky protein from the heart without the need of cleaner cells. Our work is doable and will create therapeutic options for AL amyloidosis patients that could cure their disease.
Every year, over 25,000 people need to have a stem cell transplant to treat their blood cancer. While this can cure their cancer, it also weakens the immune system. A weak immune system is a problem because it means people get more infections and can experience other complications like their cancer coming back. When we are healthy, our gut is filled with helpful bacteria. During cancer treatment, many patients lose these helpful bugs. Patients who lose the good bacteria after they have a transplant, don’t recover as well as patients who keep their helpful bugs. These good bacteria are needed for strong immune system recovery. We are working in the lab to find new ways to support healthy bugs during cancer treatment. We think this will help the patients’ immune system. Having a healthy immune system means fewer infections and a longer life. If successful, this research could lead to new treatments that help patients feel better during their transplant, avoid infections, and live longer. In the future, we will run clinical trials in transplant patients, which will lead to new standard treatments.
Funded by the 2025 Kay Yow Cancer Fund Final Four Research Award
Ovarian cancer is hard to treat. Most patient’s cancer comes back after standard treatment. Once the disease is back it is more difficult to treat and patients will eventually die from it. Chemotherapy can also cause direct harm to the body. This can make patients delay treatment, stop it altogether, or lower their doses. It can also harm the good bacteria in the gut, which is important for how well treatments work. Our goal is to come up with new ways to predict, prevent, and manage these harmful effects. We also want to develop new therapies that can lead to complete and lasting responses, increasing chances of cure right from the start. To reach this goal we will use mathematical modeling. This will allow us to test many treatments quickly, which cannot be done with traditional laboratory methods. First, we will use patient blood samples to predict the risk of toxicity, helping doctors know when to change or pause treatment. Next, we will use math modeling to find the best combinations of new targeted therapies. Finally, we will reduce the harmful effects of chemotherapy on the gut using math modeling to improve how well those therapies work. This research could change how we treat cancer. It may lead to complete tumor response and better chances for a cure.
Funded by the V Foundation Wine Celebration in honor of Mike “Coach K” and Mickie Krzyzewski
Pancreatic cancer is the third leading cause of cancer death in the United States. Treatments have changed very little in recent years. One challenge is that there are different “subtypes” of pancreatic cancer, so tailored therapies are desperately needed. Our lab found that drugs that block a protein called cyclin-dependent kinase 7 (CDK7) can kill the basal subtype, which is the most lethal. It makes up a quarter of pancreatic tumors and has the worst overall survival. We propose to study a drug that blocks CDK7 in patients with early-stage pancreatic cancer, after chemotherapy and before surgery. This funding will allow us to work with Carrick Therapeutics, who is giving us a supply of drug for the clinical trial. Our ultimate goal is to offer a new targeted treatment option and hope to pancreatic cancer patients.
Funded by Kelly Chase and the St. Louis Blues Alumni Puck Cancer charity hockey game in support of Hockey Fights Cancer powered by the V Foundation
This proposal presents a plan to collect and manage blood samples from patients getting stem cell transplants. In this treatment, unhealthy blood-forming cells (stem cells) are replaced with healthy ones. With help from the V Foundation, this research will set up and manage a new system for storing these transplant samples at Washington University in St. Louis. The study will look at detailed biological data from 40 patients who receive these transplants. These patients will have different types of donors: siblings who match, unrelated donors who are matched and unmatched, and partially matched family members. The goal of the transplant sample storage program is to help researchers at Washington University find ways to make stem cell transplants safer and more effective for treating blood cancers.
This research will also help understand how new drugs that suppress the immune system work. With the support of the V Foundation, this project supports their mission to defeat cancer.
Funded by the St. Louis Blues in support of Hockey Fights Cancer powered by the V Foundation
Therapies that modulate the immune response avoid the harmful side effects of standard cancer therapies and also have the potential to be more effective and longer-lasting. The most successful immune therapies to date rely on engineering a specific type of immune cells, T cells, to target and kill cancer cells. These therapies can be curative for some, but unfortunately still do not achieve their potential of cure for most. Our lab has identified a specific molecular pathway responsible for controlling the function of these immune cells. The goals of this project are to first understand how the driver of this pathway, a protein called BACH2, regulates engineered T cell function. Second, we aim to use advanced protein engineering tools to control the activity of BACH2, allowing us to thereby control engineered T cell function at will. If successful, these studies will shed light on a previously under-appreciated pathway that lies at the center of T cell function. Further, they will layout a pathway for “remote control” of BACH2 and nearly any T cell molecular program, allowing precision control of this potent anti-cancer therapy.
Funded by the Stuart Scott Memorial Cancer Research Fund
Pancreatic cancer is an extremely deadly disease, due to its ability to spread to other organs early and easily, a process known as metastasis. Molecules called purines are often used to build DNA and have been shown to be used by cancer cells to grow and survive. Pancreatic cancer usually spreads to the liver, an organ rich in purines. We find that pancreatic cancer cells, which contain mutations in certain genes involved in cell growth, prefer to use purines to uncontrollably grow and survive. Our study will identify how metastatic pancreatic cancer cells use purines to spread and survive in organs such as the liver. We will also test FDA-approved drugs used to treat other purine-dependent diseases such as gout and metastatic breast cancer to treat pancreatic cancer addiction to purines.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Immune checkpoint inhibitor therapy (ICT) is a form of cancer therapy that boosts the immune system to kill cancer cells. ICT can help cure some adult cancers but has not been effective in children with cancer. This proposal explores whether a combination of standard cancer therapy and ICT is both safe and effective in children with solid tumors in a clinical trial. First, we will test tumor, blood, and stool samples collected from patients in this clinical trial. We will attempt to learn what factors determine whether a patient will respond to this combination therapy or not respond. Second, we will use mouse cancer models to test different combinations of standard cancer therapy and ICT to see which combinations work the best. This work will help us understand if combining standard cancer treatments with ICT is both safe and effective in children with solid tumors.
Cancer cells often change their DNA to make more of the genes that help them grow and spread quickly. They do this with special proteins called transcription factors that read DNA, and helper proteins that change the DNA to work better. In prostate cancer cells, a protein called androgen receptor (AR) is the main cause of cancer growth. This is different from how AR works in normal prostate cells, where it helps the prostate develop properly and stops extra growth. We don’t know exactly how AR’s function changes in prostate cancer cells. My research tries to figure this out. With help from the V Foundation Award, my team will study a new protein called NSD2 that works with AR. Notably, NSD2 is only found in prostate cancer cells, not the normal ones. We’ll also test a new drug that stops NSD2 from working and see how well it kills cancer cells in different types of prostate cancer. This research will help us find more proteins that make AR cause cancer and create new medicines that target NSD2 to treat prostate cancer.
