State: New Yorkdfdhd

Funded by the Dick Vitale Pediatric Cancer Research Fund

B-cell acute lymphoblastic leukemia is the most common type of leukemia in children. New immune-based treatments have greatly improved care for many patients. These treatments work by finding markers on the surface of leukemia cells. The markers act like name tags that help the treatment find and kill the cancer cells.But leukemia cells can sometimes escape. They may lower or change these markers, making them harder for treatment to see. When this happens, the cancer may stop responding and can return.Our project will study how leukemia cells control these markers and how they hide from treatment. We will also test whether medicines can help restore the markers and make leukemia cells easier to find and kill. In addition, we will study why resistance develops when different immune-based treatments are used one after another.Our goal is to help these treatments work better and for longer. If we can keep leukemia cells visible to treatment, we may be able to reduce relapse and improve the chance of lasting remission. This work may also help doctors choose the best order or combination of treatments for each patient. In the future, these findings could lead to better and more durable treatments for children living with leukemia.

Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Hockey Fights Cancer and Jeffrey Vinik

Neuroblastoma is a childhood cancer that can be very hard to treat, especially when it comes back after therapy. Many tumors rely on a powerful cancer gene called MYCN, but we still do not fully understand how cancer cells keep MYCN active. Our research focuses on a group of proteins, called MSI1 and MSI2, that help cancer cells make the proteins they need to grow and survive. We have discovered that MSI1 and MSI2 act like a control switch for cancer cells. It helps turn on the production of important cancer-driving proteins, including MYCN. We also found that MSI2 is regulated by another process called arginine methylation, which changes how MSI2 works inside the cell. This gives us a new way to understand how cancer cells control growth at a deeper level. In this project, we will study how MSI proteins help neuroblastoma cells grow and change their identity. We will also test new treatment strategies that block MSI2 and the enzymes that control it. Our goal is to stop cancer cells from making the proteins they need to survive. This research may lead to new treatments that target cancer in a different way—by blocking how cancer cells make key proteins rather than just targeting genes. In the future, this could improve outcomes for children with high-risk neuroblastoma by slowing tumor growth and reducing relapse.

Funded by the Dick Vitale Pediatric Cancer Research Fund

Diffuse midline glioma (DMG) is a serious brain tumor that mainly affects children. These tumors often carry a genetic change called H3K27M, which helps drive the disease. However, we still do not fully understand how DMG cells use nutrients to support their growth.Our early research shows that DMG cells use unusually high amounts of three amino acids—leucine, isoleucine, and valine. These nutrients are known as branched-chain amino acids, or BCAAs. We also found high levels of BCAT1, an enzyme that helps break down BCAAs. When BCAT1 is reduced, DMG cells do not grow as well in the laboratory.This study will examine why DMG tumors depend on BCAAs and BCAT1. We will track how tumor cells use these nutrients and study what happens when BCAT1 is blocked. We will also test whether lowering BCAAs in the diet could slow tumor growth. Similar diets are already used safely in children with certain metabolic disorders.Our goal is to identify a new way to limit DMG growth and, ultimately, help patients live longer.

Our immune system has special cells called T cells that can recognize and attack cancer. Even though these tumor-fighting cells are often present, many tumors still grow because T cells stop working properly during cancer development. Cancers can be grouped into two main types based on how the immune system responds. Some are called “hot” tumors. In these cancers, T cells are able to enter the tumor, but the tumor environment weakens them so they cannot kill cancer cells. Other cancers are called “cold” tumors which comprise approximately half of all human cancers. In cold tumors, T cells are mostly missing from the tumors. Cold cancers do not respond well to immune-based treatments. Scientists still do not fully understand why T cells fail to enter cold tumors or why these cancers resist treatment. To study this, we created preclinical mouse models in which tumors grow naturally and show cold immune phenotypes. Using these models, we found that tumor-fighting T cells are present in nearby lymph nodes but do not move into the tumor. Over time, these T cells become resistant to immune treatments, which is linked to the loss of important genes needed for T cell function. In this project, we will study in mice and patients with cancer why T cells get stuck, fail to enter tumors, and stop responding to treatment. This research may lead to new ways to make immunotherapy work for patients with immune-cold cancers.

Myelodysplastic syndromes (MDS) are a group of blood cancers that cause low blood cell counts. The most common problem is anemia, which means the body does not have enough red blood cells. This can make people feel very tired and often leads to the need for blood transfusions.In MDS, the bone marrow (where blood cells are made) shows higher levels of inflammation. The cells in the bone marrow produce proteins that increase this inflammation in the body. In this project, we aim to reduce inflammation by targeting a key system called the inflammasome. The inflammasome is a group of proteins that helps to produce a substance called IL-1beta, which can make the disease worse.We are studying a new drug called HT-6184 in our lab. This drug helps block the inflammasome and reduce inflammation. In early lab tests, it has lowered inflammation and increased red blood cell levels.In this study, we will first identify the proteins and cells that cause increased inflammation in MDS. Then, we will test ways to block these targets using antibodies and specific drugs in lab-grown cells and patient blood samples. Most importantly, we will test how well the inflammasome-blocking drug works in MDS blood samples and in mouse models of the disease. This drug has already been approved by the FDA for clinical trials.If our results are successful, this research could help move this drug quickly into clinical trials designed for patients with MDS.

Cancer cells often live in a state of genetic chaos. This makes them hard to kill with existing drugs and allows cancer to spread to other parts of the body. We wanted to find out why this happens so we could stop it. We discovered that this chaos helps cancer cells hide from the body’s immune system. Usually, the immune system finds and kills cancer cells, but these cells stay invisible. To fix this, we created a new medicine. It targets the chaotic cancer cells but does not affect healthy cells. This drug turns the cancer against itself. Instead of hiding from the immune system, the cancer cells now send out a signal. This signal tells the immune system to come and destroy them. We are now testing this new medication on different types of cancers that are otherwise difficult to treat. If it works, it could lead to new treatments that save many lives.