State: Pennsylvaniadfdhd

Our immune cells help us fight injections, for example, the flu. Our immune cells also help our bodies fight cancer cells. Famous studies by Drs. Allison and Honjo, where they did experiments by injecting cancer cells into mice to study how the immune system fights cancer discovered “ways” cancer cells use to hide from immune cells. Those discoveries were then used to make drugs that “wake-up” the immune system; those drugs are known as immunotherapies. But these drugs don’t work for all patients. This means there are other “ways” cancer cells hide from our immune system. Our goal is to discover these other ways, but not by using cancer cells. Instead, we are doing experiments using unique and special cells that are not cancer yet, but on their way to becoming cancer. We call them “pre-malignant” cells (pre-malignant = pre-cancer). By using these unusual and novel cells, we want to discover new ways that cancer cells use to escape from the immune system and to make drugs that reverse this, so we can develop the next generation of immunotherapies.

Basal-like breast cancer is one of the most dangerous types of breast cancer. It is hard to treat because many cancer drugs do not work well against it. This cancer is common in people who inherit certain harmful gene changes, but it can also affect people with no family history of the disease. Today, treatment often includes chemotherapy or surgery to remove breast tissue. These options can be difficult for patients and do not always stop the cancer. Better ways to prevent and treat this disease are needed.Our research looks at the early changes that happen before this cancer forms. We created special mouse models to study how the disease begins. Using these models, we found an early change called chromatin priming. During this step, normal breast cells start to act differently and become more likely to turn into cancer cells. Changes in the way DNA is packed inside cells make it easier for genes linked to cancer to switch on. We also found that the same genes are active in both inherited and non-inherited forms of basal-like breast cancer. This means the two forms of the disease may start in similar ways.Our next goal is to learn what causes these early changes and how they lead to cancer. If we can block these changes, we may be able to stop tumors from growing. This work could lead to better treatments and better outcomes for patients.

Funded with support from Calhoun Associates
Abeloff V Scholar * (Tie for Top Rank)

Acute myeloid leukemia is an aggressive blood cancer. It affects thousands of people every year and often returns even after the newest targeted drugs. We have learned that, instead of dying, some cancer cells can “change their identity” to become a new blood cell type. These cells are called monocytes and they are able to escape therapy. This switch is like a costume change in a play: when the spotlight of treatment is on them, cancer cells put on a monocyte costume to hide. Later, when treatment eases, they can take off the disguise and return as cancer cells. We will test if these monocytes can turn back into cancer cells and cause disease to come back. We want to know how these cell changes happen and what helps them survive therapy. To answer these questions, we use new models that mimic patients’ cancer. We track how cancer cells looking at cell identity and genetic mutations. We also test new ways to block survival strategies, such as stopping the cells from becoming monocytes, in hopes of making current treatments work better and longer. By understanding and blocking the ways cancer escapes treatment, our goal is to develop strategies that keep patients in remission and improve survival.

Funded by the Maui Hui

Melanoma is the deadliest type of skin cancer because it can spread from the skin to organs like the lungs and liver. This spreading, called metastasis, can cause organ failure and is the main reason people die from melanoma. Some melanoma cells can hide in these organs in a quiet or dormant state for decades. While dormant, the cancer is not growing and cannot be found or treated. Later, these hidden cells can wake up, grow quickly, and form deadly tumors. Current treatments, including immunotherapy (which helps the body’s immune system fight cancer), often fail once melanoma returns.Most research uses young mice to study how melanoma spreads and to test treatments. But melanoma mostly affects older adults. The average age of diagnosis is 65 years-old. This mismatch means many treatments may not reflect how melanoma acts in older patients, which makes up most of the melanoma cases.Our research shows that age plays a key role in melanoma spreading. In young mice, melanoma cells that reach the lungs and liver often stay dormant. In older mice, the same cells wake up and form aggressive tumors. We show that this happens because the immune system gets weaker with age. We found that aging raises certain proteins that block the immune system from stopping cancer. Increasing these proteins in young mice causes cells to wake up and promotes aggressive cancer.This project will test if blocking these proteins can stop melanoma from coming back, spreading, and help current treatments work better.