Sita Kugel, Ph.D.

Few words inspire more fear than “pancreatic cancer,” and for good reason. Pancreatic cancer is the third leading cause of cancer death in the United States and treatment regimens have changed little, despite these poor outcomes. Researchers have learned a great deal about the genetic mutations that give rise to pancreatic cancer. Yet, we still struggle to apply this information towards more effective treatments. An enormous challenge is that there are different “subtypes” of pancreatic cancer, which makes designing tailored treatments complicated. While studying individual pancreatic cancer subtypes, our lab identified a drug that can selectively kill the most lethal subtype of pancreatic cancer at extremely low doses. This subtype, referred to simply as QM, makes up ~25% of pancreatic tumors and has the worst overall prognosis of all subtypes. Further, because the drug works at such low doses, we may be able to treat patients at doses that do not cause significant toxicity. Here, we propose to define the details of how this drug kills QM pancreatic cancer cells. We will also test whether it can treat pancreatic cancer in mouse models. Finally, we will identify ways that cancer cells could develop resistance to this drug, a frustratingly common outcome. What we learn could help to develop modified versions of the drug or possible combination regimens to overcome resistance. The ultimate goal of our research is to identify new therapies that can be tested in clinical trials.

Seth Pollack, M.D.

Synovial Sarcoma is a cancer that affects 800 Americans every year, generally teenagers and young adults. Although it can be cured if caught early, it often spreads though-out a patient’s body making it very difficult to eradicate. A new type of therapy, known as immune checkpoint inhibitors, can unleash anti-tumor immune responses against many types of cancer. But these treatments are not effective against Synovial Sarcomas. We think this is because immune cells rarely enter the tumor, and the few immune cells that are nearby cannot “see” the tumor. We have worked to address this barrier and our early findings suggest that combining checkpoint inhibitors with an old drug called interferon gamma can empower immune cells to eliminate Synovial Sarcoma.

In our new project, we will test the interferon + checkpoint inhibitor combination in a clinical trial. Using tumor and blood samples from patients, we will perform a thorough analysis of both tumor and immune cells in order to learn how to make this therapy work better and for even more patients. While Synovial Sarcoma is a rare cancer, there are other cancer types that seem to be resistant to checkpoint inhibitors for similar reasons, and our findings will likely be broadly applicable.

Parveen Bhatti, Ph.D.

Funded by Medifast, Inc.

Working outside the regular hours of 7am to 6pm, or shift work, has become a critical component of our 24-hour society. With approximately 18% of workers in the US engaged in shift work, the possibility that working at night causes cancer is an important public health issue. While increased cancer risks have been observed among shift workers, the specific factors responsible for the increased risks remain unknown. Identifying these factors is crucial to the development of strategies to prevent cancer among shift workers. Sleep disruption is thought to be a likely causal factor, but little research has been done, and studies thus far have relied on crude measures of sleep disruption. By looking at DNA damage among shift workers and using detailed measures of sleep quality, our study will, for the first time, closely examine the cancer causing role of sleep disruption among shift workers. Though sleep disruption occurs commonly among shift workers, it is not unique to them, so findings from this study will be broadly useful to the protection of health and well-being across the general population. 

Andrew Hsieh, M.D.

V Scholar Plus Award – extended funding for exceptional V Scholars

Our research is important because we study a new uncharted realm of gene expression in cancer call mRNA translation. This significantly understudied field is poised to reveal new insights into what makes cancer so difficult to treat and identify completely new ways to treat them. Our laboratory has developed new technologies to study this process in cancer. For example, we specifically focus on late stage prostate cancer which leads to approximately 26,000 deaths per year in the United States. Through the generous support of the V Foundation, we have developed a tool box of advanced staged prostate cancer models and have discovered that mRNA translation plays a key role in this disease. Furthermore, we have developed new sequencing based technologies to study the parts of the human genome which regulate mRNA translation in cancer. Importantly, we are rapidly discovering that our work applies not only to prostate cancer, but to all human malignancies. Ultimately, we aim to develop new drugs to target mRNA translation. If we are successful we will break open completely new ways to think about and treat incurable cancers.

Kevin Cheung, M.D.

Funded by Hooters of America, LLC

Metastatic breast cancer is a result of breast cancer cells that spread to and grow in other organs. It is one of the most feared consequences of breast cancer, and the main cause of death from this disease. Yet, we still do not know what causes breast cancer cells to spread and become resistant to cancer treatment. For years, researchers have attempted to learn what makes individual cancer cells within tumors most able to migrate and grow elsewhere. My lab recently found that the cells that are the most successful at metastasizing do so as clusters. Clusters are also more resistant to cancer treatment. In this project, we will evaluate the different ways that tumor cells within these clusters communicate with each other. By studying these signals, how they are transmitted and their consequences, we may uncover the key vulnerabilities needed to disrupt and destroy tumor cell clusters. We will take advantage of a technology we invented that allows us to study ‘mini-tumors’ in a dish. We will also analyze the genetic code of the various cell types in the mini-tumors. We will then cross-reference what we learn with very large studies of breast cancer patients. Through shifting our mindset from the individual to the collective, our ultimate goal is to identify new leads for the development of therapies to treat – or prevent- metastasis so that we can save lives. 

Andrew Hsieh, M.D.

Prostate cancer is the most common cancer among men in the developed world and there is currently no cure for its most deadly and advanced form, castration resistant prostate cancer (CRPC). The pervasiveness of this disease, particularly in minorities such as African Americans, highlights the importance of studying prostate cancer progression in order to develop effective new treatments. Historically, cancer research has focused on understanding how normal cells become cancer cells by accumulating alterations in DNA and RNA, the genetic material of a cell. However, these studies focus on only part of the overall process of gene expression, and neglect to take into account the ultimate end process of gene expression, protein production. Exciting discoveries from my lab and others have shown that the protein synthesis machinery is essential for cancer. This process can be hijacked by cancer, leading to grave consequences such as metastasis and drug resistance. Moreover, we have found that there is a remarkable therapeutic opportunity to drug cancerous protein synthesis without affecting normal cells in the body. The primary focus of our laboratory is to understand the fundamental connections between cancer and its protein making factories.  We will employ a convergence of state-of-the-art genetic tools and genome-sequencing strategies to study how abnormal protein production leads to CRPC and drug resistance. Our studies will help identify patients whose cancers are addicted to aberrant protein synthesis and will accelerate the development and application of cancer therapies that target this poorly understood, but vital cellular process in cancer patients.




Harlan Robbins, Ph.D. & Miriam Gutschow, Ph.D.

Funded in Collaboration With

Stand Up To Cancer (SU2C)

The last two decades have seen the development of increasingly effective cancer therapies that target different facets of transformed cells, including aberrant proliferation/survival, immune evasion, hyper-activated signaling pathways and dysregulated transcriptional programs. In a subset of cancers, including acute myeloid leukemia (AML) and non-small cell lung cancer with activating EGFR mutations, these therapies lead to dramatic clinical responses in a significant proportion of patients.

However, in the majority of AML and EGFR mutant lung cancer patients who respond to anti-cancer therapies, therapeutic relapse subsequently ensues, although often after a considerable interval, such that these responses do not lead to long-term cures. Often the relapsed tumors are infiltrated by adaptive immune cells (T cells). With the advances in immunotherapy, which utilize a patient’s own immune system to fight the cancer, it is possible to treat with immunotherapy after relapse. We are studying the T cell infiltrates before, during, and after relapse in both AML and NSCLC patients to determine if the response if the relapsed tumors have the characteristics of an immunogenic tum.

Aude Chapuis, M.D.

Research has advanced new anticancer drug therapies, saving many lives, but it is estimated that cancers will still kill more than half a million Americans specifically African and Hispanic Americans. New, safe and effective treatment approaches are urgently needed. Especially promising are treatments including cancer cells, through a large family of proteins called “T cell receptors” (AKA TCRs) which bind particular molecules associated with tumors Dr. Chapuis is an expert in identifying tumor antigens, genetically engineering matching TCRs, putting them in T cells and then infusing these enhanced methods to develop new engineered T cell therapies for patients for whom best available therapies are simply inadequate. For patients with non-leukemia patients, further optimizing methods that can also be used to target other antigens in tumors where WT1 is not expressed. She also proposes therapy after the safety of each is established for a broader future impact, including for other patients with urgent needs.

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