State: California

Prostate cancer is the second most frequently diagnosed cancer worldwide. In the US,
more than 230,000 cases are diagnosed yearly, affecting 1 in 7 men. If detected early,
the cure rate for these cancers is high – nearly all patients will be disease-free after five
years. However, in patients whose cancers either re-appear after treatment or spread to
other organs, therapies are limited mainly to symptomatic relief. Patients diagnosed at
this stage usually live no longer than 20 months. Therefore, a major challenge in treating
advanced prostate cancer is that the standard therapies, including radiation and
medicine, are not effective in killing these cancer cells.

A small proportion of tumor cells, known as cancer stem cells (CSCs), is particularly
important in promoting cancer, because they 1) can give rise to an entire tumor from a
single cell, and 2) are more resistant to treatment than other tumor cells. Efforts to
identify and then kill CSCs hold the key to effective prostate cancer treatment. The goal
of our work is to define the molecular mechanisms that drive growth of prostate cancer
CSCs. Once identified, those factors could serve as “biomarkers” or diagnostics. In
addition, drugs could be designed to target those factors as a way of blocking tumor
growth.

2016 V Foundation Wine Celebration Volunteer Grant

in honor of Pack and Susan and Sheryl Warfield

EBV infects over 90% of the population. It causes infectious mononucleosis (“mono”) among adolescents and 200,000 cancer cases worldwide every year. People infected by EBV may develop Burkitt lymphoma, a disfiguring disease common in children in Africa, Hodgkin lymphoma, head-and-neck cancer, and stomach cancer. EBV infection is typically mild but the virus remains in the body. It can become active again and cause disease in people with a weakened immune system, such as transplant or AIDS patients.
Diagnosis and treatment of cancer related to EBV infection can be difficult. Even though we have known EBV causes cancer in humans since 1965, no vaccine exists. Scientists agree on the urgent need to develop one. Our goal is to develop a safe and effective vaccine to prevent and cure EBV-driven cancers.
We will develop a vaccine using virus-like particles (VLPs). When a person receives the VLP-vaccine before EBV infection, the body will prepare itself to fight infections with antibodies. Also, immune cells will be ready to identify and kill cancer cells hiding EBV. We know our VLP-vaccine works in mice. We will repeat our work in an improved mouse model that has human immune cells. We predict that VLP-vaccine will cause antibodies to be made and will prepare immune cells to fight EBV infection and cancer cells.
If successful, we will test the vaccine in healthy patients to prove its safety. Then, clinical trials in EBV-infected patients will test if the vaccine works, before it is used in the clinic.

Ovarian cancers are among the most deadly cancers for women. We need better drugs to treat women with ovarian cancer. Recent studies show that certain ovarian cancers have mutations in unique genes. For example, 60% of epithelial ovarian cancers (EOC) have mutations in the ARID1A gene. This is an important clue to understand EOC and how to treat it. ARID1A mutation forces these cancers to rely on the related protein ARID1B. ARID1B is thus an attractive target for drug discovery. ARID1A and ARID1B are proteins that control gene transcription. However, we do not why ARID1B is vital for ovarian cancers. Using new methods, we will find the genes that ARID1B controls in EOC. We will design a system to eliminate ARID1B in EOC to test if ARID1B is a good drug target. Cancers can often find ways to escape our drugs and come back. We will find loopholes that ovarian cancers use to escape ARID1B elimination. Our goal is to find new strategies to treat women with ARID1A mutant EOC.

Funded by the 2015 V Foundation Wine Celebration

Blood cancer affects thousands of individuals each year, and despite impressive early therapeutic advances, cure rates for most blood cancers have reached a plateau. Moreover, most therapies that are currently used do not specifically target blood cancer cells and therefore lead to undesirable side effects in a large number of patients. There is therefore an urgent need for developing safer new drugs for this devastating disease. The focus of this research proposal is to define the molecular mechanisms of a specific sub-type of acute myeloid leukemia that mostly affects children and young adults but is also seen in older patients. In this project, we will make use of molecular, genetic and biochemical methods to identify ways and means by which genes that are mis-regulated in these tumors lead to cancer development. Based on our preliminary findings, we propose that our approach may lead not only to a more detailed understanding of this specific sub-type of blood cancer, but also to novel treatment strategies.