State: New York

FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND

Understanding young women’s breast cancer is a public health priority. In the United States, the rate of metastatic breast cancer is rising faster in women aged 25-39 compared to older women. Pregnancy is associated with an increased risk of breast cancer for 10 years after birth. Being diagnosed with breast cancer during this period is called postpartum breast cancer (PPBC). PPBC tumors are often more life threatening. Also, while breastfeeding reduces breast cancer risk, we do not know how breastfeeding impacts PPBC. Identifying unique tissue features within the PPBC tumor could lead to better outcomes. We will use the New York Breast Cancer Family Registry to analyze tumor tissue from 150 women. 50 samples from women diagnosed with breast cancer less than 5 years from childbirth (PPBC cases). 50 samples from women diagnosed more than 10 years from childbirth. 50 samples from women diagnosed who have never given birth. We will stain the tumor tissue with four biological markers. These markers have been associated with the spread of breast cancer and death from breast cancer. Staining, or adding coloring, to the tumor tissue will help identify unique features across the breast cancer cases. 

Aim 1: Identify unique features within the tumor samples using the four markers in 150 cases. 

Aim 2: Examine if the unique features predict breast cancer clinical features in 150 cases. 

We know little about the PPBC tumor tissue. Identifying unique tissue features that map to the PPBC tumor can improve survival outcomes for young adult patients. 

Funded through the Stuart Scott Memorial Cancer Research Fund by the Marks Family in honor of Lisa Curtis

The human body is estimated to remove over a billion cells every day, a process achieved by a relatively rare population of cells called phagocytes. When a phagocyte ingests a dying cell, it essentially doubles its content (analogous to a neighbor moving into your house). Yet, phagocytes such as macrophages often ingest multiple targets in quick succession. How these phagocytes maintain their homeostasis and manage the excess influx of dead cell cargo, are interesting scientific problems that are largely unexplored. This is an important topic in understanding cancer development broadly, and the development of cancer therapies specifically, because the clearance of cancer cells directly establishes an environment for the tumor to grow. Exciting avenues of therapy involve trying to either break down this tumor-promoting environment or by increasing the immune response against the tumor. These approaches show much promise; however, they often only work in specific patient populations. We believe that to develop a more effective therapy, we must understand the underlying processes that link clearance of cancer cells to generating an anti-cancer immune response. To this end, my lab focuses on studying phagocytes that are prevalent in Triple-Negative Breast Cancer (TNBC), how tumor cell clearance contributes to TNBC progression, and discovering new ways to target these cells to treat TNBC.  

Funded by the Constellation Gold Network Distributors in honor of the Dick Vitale Fund

Leukemia is the most common cancer among children in the US. It is also the leading cause of death from cancer before 20 years of age. Despite advances in diagnosis and treatment, a subset of leukemias affecting infants predict poor outcomes. Leukemic cells in these patients carry a fusion gene known as MLL rearrangement (MLL-r). MLL-r is critical for the development of leukemia cells, and has been well studied over the years. However, current therapies targeting MLL-r showed modest clinical activity. Therefore, there is a need of finding additional drug targets. We have found a previously unknown protein complex required for the survival of MLL-r leukemic cells. In this project, we propose to test if blocking this complex delay the growth of MLL-r leukemia in cells and animals. We will also investigate the molecular mechanisms behind. Taken together, our work will provide preclinical evidence for a new protein complex as a potential target for MLL-r leukemias. More broadly, our technologies will help the study of other childhood cancers.  

Abeloff V Scholar * (Three-way Tie for Top Rank)

Melanoma is an aggressive form of skin cancer that frequently spreads (metastasizes) to other organs. While some patients with metastatic melanoma benefit from novel drug therapies, such as immunotherapies, which reinvigorate the body’s own immune system to detect and eliminate cancer cells, most patients do not. Interestingly, patients who have metastasis to the liver are significantly less likely to respond to immunotherapies, and the underlying reasons are unclear. Here, we established a melanoma mouse model that, similar to patients, experiences liver metastasis, and therefore enabling us to study the impact of these lesions on responses to immunotherapies. We use cutting-edge methods, such as genome-editing tools and high-resolution molecular profiling and imaging methods to dissect both how liver metastases develop and how they impact the immune system in the entire body. The ultimate goal of this work is to develop improved therapies for melanoma patients with metastases to the liver. 

Lung cancer is the leading cause of cancer-related death worldwide, killing more than breast, prostate, colon, kidney, and liver cancer combined. Lung adenocarcinoma (LUAD), the most common type of lung cancer, alone kills ~60,000 Americans every year. Therefore, preventing lung cancer would have a large impact on society. Preventing lung cancer altogether would also address the problem of worse outcomes for patients who, for social and economic reasons, have unequal access to cutting-edge cancer treatment. Even patients who are cured of cancer experience psychological trauma, so prevention would also mean that no one would have to go through such a traumatic experience. Our initial results show that early lung cancers are less complex and therefore should be easier to eliminate compared to advanced disease that has spread from the lung to other parts of the body. We propose to study the earliest steps, when a normal lung cell becomes a cancer cell. To do this, we have developed a way to study lung cancer cells in the lab that closely resembles how tumors grow in humans. In addition to studying features of early lung tumor cells, we will also study the surroundings of these cells, a method that has not been used before to study lung cancer. We aim to discover molecular processes that are essential for the formation of lung cancer. Drugs could then be developed to block these processes and stop lung cancer at its earliest stages – preventing the disease altogether.

Liposarcoma is a cancer that affects approximately 1000 new people per year in the United States and primarily targets adults over the age of 50. Although some cases are successfully cured with surgery if caught early, patients traditionally had few options if the cancer came back or if surgery did not eradicate it, because standard chemotherapy and radiation therapy were not effective. A new class of drugs called CDK4/6 inhibitors has recently begun to change the prospects of these patients. These drugs stop cancer cells from dividing without killing them. In some patients, the same drugs cause the cells to enter what is called senescence: the cells never resume dividing, even when the drug is removed. Senescence normally occurs in cells whose DNA has been damaged, so this exciting new form of senescence called SAGA (senescence after growth arrest), that is triggered by a CDK4/6 inhibitor, is not as well understood. I am working with a collaborator who has begun to study SAGA in liposarcoma tumor cells. I am an expert in mapping how DNA is folded inside the cell nucleus to regulate which genes are expressed (turned on). I propose to use my mapping tools to study how the structure of the genome in tumor cells helps cells to decide whether to enter or stay in SAGA, what genes to turn on, and how we might control these genes using other drugs that can be combined with CDK4/6 inhibitors.

Inflammation is major risk factor for cancer and is directly linked to at least 20% of all cancers. Our epithelial tissues, such as the gut, lungs and skin, routinely experience injuries and infections that cause inflammation. A vast majority of inflammatory reactions resolve to restore tissue health. Many studies have examined the role of chronic (non-resolving) inflammation in cancer formation and progression. However, how routine acute or resolving inflammation influences cancer formation has not been closely studied.

We have previously shown that acute inflammation fundamentally changes tissue immune environments and epithelial stem cells. This process, called “inflammatory training”, is known to improve responses to pathogens, vaccine efficacy and, we find, enhance tissue regeneration. Using models of squamous cell carcinoma, a deadly cancer that can develop on many epithelial surfaces, we examine how inflammatory training impacts the initiation of tumors. We will study both the tumor forming cells and their microenvironment to determine exactly which factors are changed by acute inflammation that make tissues hospitable to cancer cells. In doing so, we seek to unearth fundamental knowledge of how tumors form and use this information to develop strategies for early intervention to stop this devastating disease in its tracks.