V Scholar Archives - Page 22 of 60

Qing Chen, M.D., Ph.D.

Metastasis is the spread of cancer to one or more different organs of the body from where it started. The brain is one of the common organs for cancer recurrence. Even with aggressive treatments, brain metastasis is increasingly becoming a significant clinical problem. To find new therapeutic targets to treat brain metastasis, we need to first understand the progression of the disease.

Metastases are generally site specific. The environment of each organ is different. Cancer cells may only be able to colonize one or more specific organs, depending on the primary tumor from which the cells derive. As illustrated in the ‘seed and soil’ theory, tumor cells behave like seeds that can only successfully colonize selective organs that offer the right soil for their survival and growth. Thus, we plan to understand brain metastasis by focusing on the complex conversation between cancer cells (the seed) and brain cells (the soil). Using advanced microscopy techniques, we will directly visualize the metastatic brain tumors in the living animals. Meanwhile, we will detect therapeutic responses when newly designed treatments are applied. From these studies, we will obtain dynamic longitudinal changes in the cancer cells and the surrounding brain cells. This will allow “reconstruction” of the brain metastasis process, as well as therapeutic response. We strongly believe that these studies will yield new ways of fighting brain metastasis.

Scott Bratman, M.D., Ph.D.

Many cancers are treated with radiation therapy. Some cancers types are especially hard to treat. One type of cancer that affects the lungs and throat is only cured in about half of cases. Even when drug treatments are added to the radiation therapy, cure rates are not much improved. Also, adding drugs to radiation therapy can make the treatment hard for patients to tolerate. New treatment approaches are needed for these patients.

One new approach that is showing promising results is to give refined treatments that are more precisely targeted to each patient’s cancer. This approach is called Precision Medicine. Precision Medicine has not been used much for the cancer type that affects the lungs and throat. Also, Precision Medicine has not yet been used for radiation therapy. Instead, the standard treatment for these patients continues to be a one-size-fits-all approach.

We expect that the standard one-size-fits-all treatment approach could be replaced by Precision Medicine. The objective of our research is to develop new Precision Medicine approaches for the cancer type that affects the lungs and throat for use with radiation therapy. These new treatments could someday lead to higher cure rates and tolerability of treatment. If successful, our research will lead to new clinical trials that will test these new treatment approaches in cancer patients.

Paula Bos, Ph.D.

Funded by Hooters of America, LLC

Breast cancer is the most common type of cancer in women worldwide. Metastatic disease is incurable and causes 90% of breast cancer-related deaths. Current treatments for breast cancer help patients live longer, but they have no effect once the tumor is in the brain. Moreover, by prolonging survival they increase the risk of brain metastasis over time.

Primary breast tumors secrete factors that travel through the blood and facilitate seeding and growth of new distant tumors by inducing changes in the structure of other organs. The proposed research will look at how regulatory T (Treg) cells, a type of immune cells heavily present in primary tumors, support changes in the brain tissue that allow brain metastasis to develop. To model this, we will utilize genetically engineered mouse models and surgical manipulations like the ones occurring in human breast cancer patients to investigate how the presence of regulatory T cell affect brain metastasis formation over time. Specifically, we will assess the changes in cell composition and structure of the brain tissue before metastasis develops in mice with and without Treg cells. In addition, we will evaluate changes in blood circulating factors, and establish the requirement of cells from the bone marrow and specific cytokines for the remodeling of the brain. By learning more about what happens to the brain tissue before metastases form, we hope to improve our chances of developing therapeutic strategies to prevent them.

Collin Blakely, M.D., Ph.D.

Lung cancers are often driven by genetic changes. The focus of my research is on a type of lung cancer that is driven by changes in the EGFR gene. This type of lung cancer often occurs in younger patients who are non-smokers. New medications can target these changes. This has allowed patients to live longer. However, patients are almost never cured of their disease. My goal is to understand why responses to these EGFR targeted treatments are almost never curative. Then I will work to identify new medications that can be used together with EGFR inhibitors. This may allow patients to live longer. I will accomplish this goal by identifying all of the genetic changes present in patients’ tumors. This will allow us to understand which ones may be allowing cancer cells to survive. I will also assess tumors for other changes that occur within cancer cells. In addition, I will look at the immune cells that are in the tumor. To summarize, the goal of this research is to identify new combination therapy strategies that can improve the depth and duration of response to EGFR targeted therapies, allowing patients with this deadly disease to live longer.

Ami Bhatt, M.D., Ph.D.

Funded in partnership with the SAGERSTRONG Foundation in memory of Craig Sager

There are trillions of bacteria, viruses and fungi inside each and every human. We call this the microbiome. Scientists have found that the microbiome can change how cancer grows and how people respond to cancer therapies. Our lab wants to make the lives of cancer patients better by improving their microbiomes. The usual ways to change the microbiome are through diet, antibiotics, and by eating live bacteria in food. An example of a food with live bacteria is active culture yogurt. We are doing an experiment to see if a special type of fiber can improve the human microbiome. This fiber is digested by specific bacteria in the gut. When it is digested, it is turned into molecules that control the human immune system. We are giving cancer patients this fiber to see if we can increase these immune system-controlling molecules. If this works, we will prevent the immune system from doing harm in cancer patients. We hope to help patients like those who get blood and marrow transplants for treatment of leukemia or lymphoma. Once we understand how these fibers and our microbes change the immune system, we can figure out precise ways to use this knowledge to make the immune system work better. For example, we may be able to make exciting new cancer therapies, like immunotherapy, work better.

Olga Anczukow, Ph.D.

Funded by Hooters of America, LLC

Age is the greatest risk factor for breast cancer. About 80% of all breast cancers occur in women older than age 50. Aging is associated with tissue changes as well as changes in the genes that are expressed in breast cells. However, the age-related molecular and cellular mechanisms that underlie these changes and contribute to breast cancer development remains poorly understood. Our lab studies a mechanism by which genes are read to produce different proteins, called RNA splicing. RNA splicing can generate proteins with different functions from a single gene. We previously discovered that this process is altered in human tumors and leads to breast cancer. Additionally, changes in RNA splicing also occur in healthy aging. Here we will test the hypothesis that (1) changes in RNA splicing occur in the mammary tissue with age, and (2) that these splicing changes prime the breast for tumor formation. Our research findings may provide biomarkers of breast cancer risk before the tumor develops. Our ultimate goal is to identify novel strategies for early breast cancer detection, early intervention, and prevention.

Claudio Alarcon, Ph.D.

Funded by the Stuart Scott Memorial Cancer Research Fund

Pancreatic cancer is a deadly disease. Most patients with pancreatic cancer are diagnosed at late stages. There are no impactful treatments for this disease. Patients with advanced disease only survive for a few months. There is a need for novel approaches for novel therapies. We need to understand the biology that allows cancer cells to create new tumors and invade other tissues. We propose to study the role of a new RNA modification. These changes on RNA control many aspects of the cells. Recently, the proteins that modify the RNA have been involved in several cancer types. However, the way that they act in cancer cells is unknown. We propose that the RNA changes are used by cancer cells to increase their ability to grow and invade new tissues. Thus, we propose to use multiple approaches to test the role of this RNA modification in pancreatic cancer initiation and progression. Understanding the basic mechanisms involved in the abnormal use of this RNA changes could lead to the development of novel therapies to treat cancer and metastatic diseases.

Russell Ryan, M.D.

Abeloff V Scholar*

Diffuse large B-cell lymphoma is a blood cancer that is currently treated with chemotherapy drugs. These drugs can be toxic, and do not work for all patients. Certain cancer-causing genes must be turned on in order for lymphoma cells to grow and survive. One new way to treat patients with lymphoma might be to find drugs that turn off the ‘switches’ that cancer cells use to turn genes on. This could potentially kill cancer cells without hurting normal cells.

We will study the proteins and DNA code that serve as a ‘switch’ to control two lymphoma-promoting genes, MYC and BCL6. We will use new technologies to learn how these genes are turned on, and how we can block this process. Some lymphomas contain errors in the DNA code (mutations) that alter these gene ‘switches’. We will compare the function of lymphomas with mutations to lymphomas with intact ‘switches’.

This project has two main goals. First, we seek to create new tests that can be used to find mutated gene ‘switches’ and guide lymphoma patient care. Second, we seek to find target proteins that could be used to create new lymphoma treatments.

Philip Kranzusch, Ph.D.

Abeloff V Scholar*

A new form of treatment for cancer is to activate a patient’s own immune system to recognize and destroy tumor cells. Called cancer immunotherapy, this strategy has proven to have a remarkable impact on long-term survival for patients with a wide range of cancer types, but only a subset of individuals has sustained responses that can lead to a long-term cure. In order to advance cancer immunotherapy, it is critical to understand the immune signals responsible for robust tumor immunity.

One key part of the immune response to cancer is a cellular protein named STING (Stimulator of Interferon Genes) that allows immune cells to detect DNA derived from tumors. STING naturally responds to drug-like small molecules, and an exciting new area of study is the idea of “STINGing cancer” – using compounds that specifically activate STING to boost tumor recognition and patient responses to cancer immunotherapy. In spite of the clear role of STING in immune cell responses, STING signaling is poorly understood and we do not understand how signaling leads to improved patient responses.

Our research will determine how STING transmits signals to the immune system and which STING signal is critical for combating cancer. These experiments will provide the foundation for the design of next-generation drugs that target STING and, ultimately, will help us understand how to use cellular proteins like STING to better control human immune responses and treat cancer.

Robert Signer, Ph.D.

Funded in memory of Tony Smith, EdD, Member of the V Foundation Board, 2003-2017

Blood cancers, such as leukemia, often begin in the bone marrow where rare blood-forming stem cells regenerate normal blood cells throughout life. Many blood cancers can be eliminated with chemotherapy, but chemotherapy also destroys normal stem cells. Thus, many cancer patients depend on receiving stem cell transplants after therapy. Sadly, many patients are unable to receive life-saving transplants because of insufficient numbers of available stem cells. One way we can overcome this challenge is to develop ways to grow and expand blood-forming stem cells outside the body, but previous efforts to do so have been unsuccessful. Recently, we discovered that stem cells make new proteins much more slowly than other blood cells, and this slow rate of protein production is crucial for stem cell function. Proteins are the functional products of genes and perform many specialized tasks within cells. Making proteins too quickly increases assembly errors leading to the production of dysfunctional and toxic proteins. In contrast, producing proteins slowly helps ensure that new proteins are precisely assembled, are of high quality and function correctly. We found that growing stem cells outside the body increases the rate of protein assembly and decreases protein quality, which impairs stem cells. We are using new and innovative strategies to enhance protein quality within stem cells that could, for the first time, enable expansion of blood-forming stem cells in the laboratory. These discoveries could provide new therapeutic possibilities for numerous cancer patients.