State: Massachusetts

Abeloff V Scholar * (Tie for Top Rank)

Pancreatic cancer is one of the deadliest cancers. A condition called pancreatitis, which is prolonged inflammation of the pancreas, increases the risk of getting this cancer. For over 100 years, scientists have known that both pancreatitis and pancreatic cancer involve many nerves. But only recently have we started to learn that these nerves may actively cause pain, increase inflammation, and help cancer grow through direct interactions with cancer cells but also indirect effects on the immune system. However, we still do not fully understand how this works, and there are no treatments yet that target these harmful nerve-cancer interactions.Our research focuses on a type of nerve cell called a nociceptor. These nerves sense pain and use a protein called Nav1.8 to send signals. A new drug that blocks Nav1.8 was recently shown to be safe and helpful in reducing pain after surgery. In our project, we will test whether blocking Nav1.8 can also reduce pancreatic inflammation and slow cancer growth. We will also study how damaged nerves affect the immune system. Our early data suggests that injured nerves can change certain immune cells called macrophages, causing them to block T cells from attacking the tumor. Our overarching goal is to find new ways to prevent and treat pancreatic cancer by targeting the nerves that drive pain and disease. We hope these treatments will ease pain, stop cancer from forming or growing, and help patients live longer.

Acute myeloid leukemia (AML) is a deadly blood cancer that’s difficult to treat. Sometimes AML starts with a mistake in our cells. Think of DNA like a library of instruction books for your body. Imagine if pages from two different books accidentally got glued together—that’s what happens in AML when two different genes get stuck together to create a cancer-causing fusion protein. These fusion proteins take over the cell’s control system and make cancer cells grow without stopping.Our research team found that we can fight these cancer-causing fusion proteins by blocking other proteins that help them work. When we block these helper proteins, the cancer cells stop growing and start turning into normal white blood cells. We’ve shown that drugs blocking a helper protein called Menin can make cancer cells change back toward normal. Doctors are now testing these drugs in patients with AML. However, we’ll probably need to use several drugs together to completely cure this cancer.Our team also found two more important proteins called KAT6A and KAT7. These proteins help write the instructions that keep cancer cells growing. We’re studying how KAT6A and KAT7 work together with fusion proteins to cause leukemia. Understanding how these proteins cooperate to cause AML will help doctors create better treatments that cure more patients while causing fewer side effects.

Funded by the Dick Vitale Pediatric Cancer Research Fund with support from Tony and Debbie DiMare

Neuroblastoma is the most common cancer in babies. It can act in surprising ways. Some forms grow quickly and are very hard to treat. Others, especially in babies under 18 months old, can shrink or even disappear without treatment. Doctors do not fully understand why this happens, but the immune system may play a key role. One type of immune cell, called the CD8⁺ T cell, is especially good at finding and killing cancer cells.This project will study whether the immune system in babies works differently from that of older children or adults, and whether these differences can explain why some tumors go away on their own. Baby T cells are often thought of as immature, but new research shows they can grow faster, work more efficiently, and resist “burning out” better than adult T cells.In our early work, we trained baby T cells to recognize neuroblastoma cells. They were better at killing these cancer cells than adult T cells. We also found that baby T cells rely on a nutrient called pyruvate for energy and function. They process pyruvate in a special way using an enzyme called GPT.We will test whether this unique metabolism is the reason for their strong performance. We will also see how the tumor environment changes T cell metabolism, and whether changing the way T cells use pyruvate can make them even better at fighting cancer.We will use umbilical cord blood as a safe, widely available source of baby T cells. If this approach works, it could lead to new cancer treatments designed for children. The goal is to make these treatments safer, more effective, and take advantage of the natural strengths of the infant immune system.

Immune therapy is a cancer treatment that turns on killer T cells to attack the tumor. It is a major advance in cancer care. As it is less damaging to healthy tissue than chemotherapy, it has fewer side effects. Most importantly, it can help patients with advanced disease who had few options before. However, many patients do not benefit from immune therapy. The reasons why are not fully understood. Cancer affects people of all ages, but it is much more common in the elderly. T cells are key to the success of immune therapy, but aged T cells do not work as well as young ones. We have discovered that a signal important for T cell function is lost as people age. The loss happens even before a tumor appears. As tumors grow, aging makes even more T cells lose this signal. Our research will test whether the loss of this signal explains why older patients do not respond to immune checkpoint therapies. We will explore ways to restore this signal to improve treatment outcomes. Through this research, we hope to make immune therapy effective for more patients, especially older adults who face the highest rates of cancer.