Grant Archive - Page 2 of 138

Lillian Guenther, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

My group investigates specific features of pediatric bone tumors that allow them to survive. One cancer we are interested in is Ewing sarcoma. Ewing sarcoma is a common bone tumor in children. It is challenging to treat, particularly when the cancer has spread. We have become interested in a protein that is important for Ewing sarcoma cells. We want to understand what this protein does in cells. This will help us to kill Ewing sarcoma cells. We are also working with chemists to make new drugs to disrupt its activity. We will test these in Ewing sarcoma cells. Our hope is that these studies will eventually lead to new treatments for Ewing sarcoma.

Markus Müschen, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Many children survive with current treatments but when the disease recurs, it is often deadly and as such we need new treatment options for these children.In most cancers, a protein called beta-catenin is highly prevalent, making cancer cells grow faster. We thought this would be true for ALL but found the opposite. In ALL, beta-catenin is kept at very low levels because the cells quickly break it down. When it does appear, it works with a partner called LEF1 instead of its usual partner, TCF7. This pair slows cancer growth and can even make the cells die.This means ALL cells are very sensitive to beta-catenin buildup. We can use this weakness to our advantage. We have found four kinds of existing drugs, already tested in people for other diseases, which block the breakdown of beta-catenin in different ways.Our goal is to test these drugs to see which works best against ALL that does not respond to chemotherapy. Because these drugs are already known to be safe, we can move faster toward clinical testing in children. If successful, this approach could give new hope to families facing relapsed leukemia.

Evan Weber, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Pediatric cancer patients have greatly benefited from CAR-T cell therapy, which is a treatment that uses a child’s own T cells – a type of immune cell – to find and kill cancer. This approach has helped many children with blood cancers, but fewer than half stay cancer-free after one year. One reason for this is that sometimes CAR-T cells don’t survive long enough in the body to stop the cancer from returning. To fix this issue, we are trying to develop ways to make CAR-T cells act more like marathon runners that stay in the fight instead of sprinters that slow down too soon.My research focuses on the bone marrow, which is the part of the body where some blood cancers hide and where CAR-T cells go to fight them. We’ve found that the bone marrow sends out special signals that affect how well CAR-T cells survive. In this project, we will study those signals and use what we learn to create longer-lasting CAR-T cells. This work could ultimately make CAR-T therapies work better for kids and adults and inform other approaches to help these powerful immune cells stay active longer.

Andras Heczey, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Special white blood cells can be engineered to fight cancer. They are engineered with a molecule call CAR. This molecule helps them kill cancer cells. The special white blood cells include T and NK cells. These cells can cure some blood cancers. They show great promise for children with solid tumors. CAR T cells often get exhausted in solid tumors. CAR T cells are currently made outside the body. This can further weaken them.Our research aims to overcome these challenges. We will target Glypican-3 (GPC3). It is a molecule found on many childhood solid tumors. We propose a new way to engineer CAR T cells inside the body (in-body). We will use special virus-like particles (LVPs). These LVPs will precisely reprogram the children’s own immune cells to fight GPC3-positive cancer. We will test “armoring” strategies of CAR T cells. This is to make these in-body generated CAR T/NK cells even more powerful and long-lasting.Our hypothesis is that in-body engineered GPC3-CAR T cells will be highly effective against cancer cells. We will first maximize the effectiveness of our LVP delivery system. Next, we will compare the different armoring strategies. We will study how they boost the survival of in-body generated CAR T cells. Finally, we will select the most potent armoring strategy. Ultimately, this research aims to bring safer, more effective CAR T-cell therapy to children with solid tumors. The findings may be applicable to other cancers in the future.

Brian Czerniecki, MD, PhD

Funded by Hooters

Breast cancer is the most common cancer type and 2nd leading cause of death by cancer for women in the US. Patients with early-stage breast cancer or DCIS can survive. But there are groups at high risk for the cancer coming back or developing invasive breast cancer (IBC). These patients are treated with surgey, radiation, and other types of therapies. While these treatments often work, recurrence and IBC are still problems. Our project aims to create a therapy using the patients’ immune system. This therapy will help the body to recognize and engage in the fight against their cancer. If successful, this therapy will be the first non-estrogen inhibitory immunotherapy. And this therapy will help prevent the cancer from coming back and prevent IBC.

Antony Michealraj Kulandai Manuvel, PhD

Funded in partnership with WWE in honor of Connor’s Cure

Supratentorial ependymoma is a rare but serious brain tumor that mostly affects children. Right now, the main treatments are surgery and radiation, but these are not always enough. Our research team is working to understand this cancer better by creating models of the tumor using samples from patients and mice. These models help us find what makes this tumor different from healthy brain cells. We’ve discovered that ST-EPN tumor cells have special dependency for their survival and growth, and we’re testing new avenue to stop the tumor from growing without harming normal cells. We also found that these tumor cells can steal more nutrients than healthy brain cells, which helps them grow faster. By using approved drugs to block this process, we hope to cut off the tumor’s energy supply. By studying real patient tumors and using mouse models, our goal is to find new and better treatments. In the future, this research could help doctors treat children with ST-EPN more safely and effectively.

Toshiro Hara, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Brain cancer is an unwelcome guest that sneaks into a kid’s brain. Doctors can usually see and take out the cancer, but it gets really difficult when the cancer enters normal brain areas. This sneaky move by cancer is called invasion. The problem is that these cancer cells are so small and tricky that even our best medical scanners can’t find them. It is like the cancer is playing a game of hide-and-seek in the kid’s brain and escaping from the doctor’s tools.We know some of the places the cancer hides, but we don’t understand why it chooses certain paths or how it moves so easily. So, what we did was take a super close-up look at how brain cancer behaves using a special research tool. This is a way to see exactly what is going on inside individual cancer cells. Our first look tells us that brain cancers are like masters of disguise — they can look like normal brain cells, especially when they are hiding among them, and it seems they might even be “talking” to the normal cells around them.We will dive deep into how these cancer cells chat with healthy brain cells and what special tools or genes they use to travel so well. We believe figuring this out could put the brakes on cancer’s sneaky move. It could lead to new treatments that stop their play and talk, making treatment much more effective and helping many kids.

Jeffrey Magee, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

My lab is working on new treatments for children with hard-to-cure cancers. We focus on a type of cancer called acute myeloid leukemia, or “AML” for short. AML accounts for about one-third of childhood leukemias. We have been less successful at treating AML than other childhood cancers. AML is challenging to treat because each patient may have different genetic mutations (alterations) causing their disease. A new drug that works for one patient might not work for another. Also, drugs that work in adult AML patients might not work well for childhood AML. To get around these problems, we create models that accurately reflect human childhood AML. We have created many different models to include the different types of mutations that patients can have. While studying these models, we discovered a protein called SPNS2 that might be a new drug target for tough AML cases. Early tests with an SPNS2 drug show promise in killing AML cells. This project aims to find out which patients will benefit most from SPNS2 drugs and see if combining these drugs with other AML drugs could improve treatment even further. We also aim to understand why SPNS2 is important in these cancers. My goals are to improve treatments and to broaden our understanding of AML in children.

Ulrich Steidl, MD, PhD

Acute Myeloid Leukemia (AML) is a fast-growing blood cancer that is very hard to treat. Fewer than 20% of patients live more than five years after being diagnosed. One big problem is that AML often comes back after treatment or stops responding to chemotherapy, which is the main reason people die from this disease. Most research has looked at genetic changes that help cancer cells resist treatment, but new studies show that non-genetic changes also play an important role.Our research focuses on one of these non-genetic factors called “transcriptional noise.” This means natural changes in how genes are turned on and off in cells. Using advanced tools that look at single molecules, we found that chemotherapy causes a quick increase in this transcriptional noise. This seems to help leukemia cells survive the treatment. When we blocked this noise—by targeting an enzyme called Pol II that controls gene activity—the leukemia cells became more sensitive to chemotherapy. We saw this in lab tests and in mouse experiments. We also found that certain “early response” genes—genes that react fast to chemotherapy—show a lot of this noise, which means they could be new targets for drugs. Our future research will try to figure out exactly which genes are involved, how this noise helps cancer resist treatment, and which types of AML can be treated better by blocking transcriptional noise. This new approach could lead to better ways to stop drug resistance in AML and other cancers, giving patients hope for more successful treatments in the future.

Christina Curtis, PhD

Why do some people get certain types of cancer, while others don’t? For some cancers, we know that inherited genes play a role. But for many, it’s still a mystery. One reason is that cancer is very complex and we don’t fully understand how a person’s genetic makeup and immune system affects their risk.In our recent research, we found something surprising. We discovered that both a person’s genes and their immune system work together to influence which type of cancer they might develop. This includes hard-to-treat types like HER2+ and ER+ breast cancer, which can come back many years after treatment.Some early changes in a tumor’s DNA can act like a warning signal, helping the immune system find and destroy these abnormal cells before they grow. But if the tumor hides from the immune system, it can become more dangerous. That’s why it’s so important to find and treat these cancers early.Our work helps to explain the role of genetic variation in cancer, even when no single gene seems to be responsible. It also points to new ways to determine who is at risk and to create treatments that are personalized—based on each person’s genes and immune system. We’re working to turn these discoveries into better tools to predict, prevent, and treat cancer more effectively.