State: California

Funded in memory of Bob Moonan

Of the cancers that affect both men and women, colon cancer is the second leading cause of cancer deaths and the third most commonly diagnosed cancer in the United States. Interestingly, evidence from the clinic links disruption of normal 24-hour rhythms with many diseases including a higher risk of cancer. Our internal clock controls sleep/wake cycles, feeding and metabolism and disruption of the clock has been reported in several cancer types, including colon cancer. Yet, the precise process of clock disruption in colon cancer remains undefined. We are interested in cells that have the ability to initiate tumors because these cells have been found to be treatment resistant. We propose to determine how loss of the clock can promote colon cancer by changing the cues that direct these cells that initiate cancer. To accomplish this, we have generated a mouse model to understand the effects of clock disruption on cell growth in the intestine. We propose that disruption of both the clock and loss of cues that control normal cells in the intestine can result in colon cancer. The goal of these studies is to provide new directions towards clock-dependent treatments that can target colon cancer.

Vintner Grant funded by the 2018 V Foundation Wine Celebration in honor of Karen Aldoroty

Immunotherapy is a very promising new treatment that uses the body’s own immune system to recognize and fight cancer. This research project focuses on immune cells called macrophages, which are a group of white blood cells in the body. Previous studies have showed that when cancer cells grow in the body, they use signals to protect themselves and escape from macrophages. When treatment was given to block these signals, macrophages were able to recognize and attack cancer cells. In the tumors, in addition to cancer cells, there are many other groups of cells including macrophages. Cancer cells can travel from the primary tumors and grow in organs such as the lung, liver and brain. This caused over 90% of cancer patient deaths. Importantly, these organs also have many macrophages. It is very important to examine if and how macrophages can be used to defend against tumor cells and thus to treat cancer. However, there is much that we do not understand about what exactly occurs during these processes. In this study, we would like to understand how macrophages and cancer cells interact with each other and how macrophages decide if or not they should attack tumor cells. This knowledge will be used to develop new immunotherapies that block cancer cells’ protective traits and allow macrophages to attack and clear them.

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.

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.