Funded in partnership with Miami Dolphins Foundation
Blood cell cancers often bear mutations in STAT3. This protein is normally beneficial but, when overactive, becomes a cancer ‘driver’. More than 150 relevant mutations have been identified but only 7 have been studied in any detail. Thus, it remains unknown how mutations alter STAT3 activity to drive blood cancers. In fact, the same can be said of most oncogenes. The capacity to identify mutations far exceeds the capacity to appraise them. Our research will directly address this problem. To that end, we have devised an experimental platform that enables us to study all known STAT3 mutations at once. This platform is scalable, new mutations can be easily added, and readily adaptable to other cancer drivers. It is also designed to be implement in mice, allowing us test drugs in vivo, across all mutants at once. Using this platform, we will advance basic understanding of STAT3 and inform treatment options for associated blood cancers.
Every year, over 40,000 people are diagnosed rectal cancer in the US. Many of these patients will receive radiation treatment. Sadly, radiation does not cure all rectal cancers. Many non-genetic, or “epigenetic,” factors control how cancer cells are built and how they respond to treatment. Often, these factors mimic biology seen in normal, non-cancer cells. Radiation causes normal intestine cells to change into stem cells that repair damage. We suspect these radiation-induced stem cells also occur in rectal cancer. We propose to test whether these radiation-induced stem cells cause rectal cancer to resist radiation. We will also map out the epigenetic factors that allow these stem cells to arise. To do this we will use new methods we have developed to show the fine details of epigenetic regulation. From our data, we will discern new mechanisms of rectal cancer radiation response. We hope these studies will yield novel treatments to combine with radiation for rectal cancer.
Funded by the Stuart Scott Memorial Cancer Research Fund
Cancer immunotherapy, which uses a patient’s own immune system to fight cancer, has been very successful for some patients. But not everyone benefits. The immune system is made up of both immune cells that are both “good” and “bad” at fighting cancer. T cells are important “good” cells because they can kill cancer cells. Macrophages, however, can limit how well T cells can kill. Our lab studies how immune cells respond to cancer. In particular, we are interested in how different regions of the same tumor can have different immune cells in them. This means that some regions can have a good immune response, while at the same time, other regions have a bad response. We want to understand how the “bad” immune response regions form and how to fix them. We have identified a molecule called Cx3cl1 that some tumor cells make, which attracts “bad” macrophages. In this project, we will use a model system to study how Cx3cl1 interacts with macrophages. We will study areas of a tumor that have lots of Cx3cl1, and what happens to them when the tumor is treated with immunotherapy. We will also look at Cx3cl1, “bad” macrophages and “good” T cells in different regions of patient tumors. Our ultimate goal is to bring a “good” immune response to all regions of a tumor, so that immunotherapy will work better.
Cancer is dangerous because it grows out of control in the body. Cancer needs to consume nutrients to make the energy to grow. We discovered that colon cancer makes energy very slowly. Because of this, we want to try blocking energy production to kill the colon cancer.
We found that colon cancer has a very low level of Vitamin B1, which is required for the major energy producing pathway in colon cancer. We will test three different ways to take away Vitamin B1 to see if this could stop colon cancer. We will also try to find why colon cancer has so little Vitamin B1. In future, if our hypothesis is right, maybe colon cancer patients could eat a diet low in Vitamin B1 to strengthen the effects of anti-cancer drugs they receive.
In recent years, colorectal cancer (CRC) has become the third most common and second most deadly cancer in the US. CRC is the leading cause of cancer death among Americans under 50 years old, but experts do not know why rates are increasing among young people. Moreover, we do not have a good way of detecting people who are at higher risk of CRC. These people should receive early monitoring and undergo extra measures to prevent CRC. How can we identify these at-risk individuals? We propose that certain bacteria cause the production of an enzyme (DUOX2) in the gut. High levels of this enzyme are found in people with gut inflammation and people with CRC. In the proposed research, we plan to test whether patients with different types of CRC have different levels of DUOX2. We expect that some CRC types will have higher levels than others. Next, we will try to identify the bacteria that lead to high DOUX2 levels. Discovering these bacteria may help to identify people at higher risk of CRC (people with higher amounts of these bacteria) and suggest new cancer treatments (ones targeting these bacteria). Finally, we will test whether drugs that are already approved for use in humans, along with other products of bacteria, can reduce levels of DUOX2 in the gut. Identifying these drugs may improve prevention and treatment for CRC.
Colorectal cancer (CRC) is the third most common cancer worldwide and ranks as the second leading cause of cancer-related deaths. Screening plays a key role in early detection and makes CRC one of the most preventable cancers. Developing an accurate risk prediction score is crucial because it helps us identify and focus on those at high risk from a young age, enabling early screening and effective intervention. Research has shown that thousands of genetic mutations can increase the risk of developing CRC. Our goal is to convert these genetic discoveries into useful tools for clinical use. We plan to utilize advanced techniques such as CRISPR screening technology and single-cell sequencing, combined with deep learning models and statistical analysis. This approach will help us understand the whole impact of these genetic mutations better. This work aims to provide deeper insights into how these mutations contribute to the development of CRC, leading to more targeted and efficient screening strategies. Ultimately, our research is directed toward developing a sophisticated method for predicting colorectal cancer risk, focusing specifically on those who are most at risk. This could significantly change how we prevent and treat colorectal cancer.
Surgery is the main treatment option for patients with rectal cancer. During surgery, the surgeon’s main goal is to completely remove cancer tissue without leaving cancer behind. However, not all diseased tissue can be seen with the surgeon’s eye, especially after radiation when tumor and scar look similar. Because of that, it is hard for a surgeon to be certain that all cancer tissue has been removed on the anal side to help preserve the anus and avoid a permanent bag. The same problem happens for adjacent organs such as the pelvic nerves, pelvic sidewall, vagina or prostate that may appear to be affected. Consequently, 4-20% of patients have recurrence while 20-50% have postoperative complications. Currently, there are no technologies that can help surgeons identify cancer tissues within the rectum and nearby organs in vivo during surgery. Surgeons are thus faced with the difficult decision to excise questionable tissue that could be affected by cancer at the devastating expense of compromising critical tissue structures and quality of life. In our study, we will evaluate the MasSpec (MS) Pen technology for tissue identification in rectal cancer surgery. The MSPen provides the transformative capability of detecting molecules diagnostic of cancer in tissues in vivo, without tissue damage. We will refine the MSPen for rectal surgery and evaluate its performance in identifying rectal cancer and normal tissues. The MSPen has the potential to help surgeons achieve complete cancer removal and preserve normal tissues, thus improving treatment, outcomes, and quality-of-life for patients.
Cervical cancer is highly preventable. However, it remains a health burden and is the fourth most common cancer in females around the world. Cervical cancer is caused by “high-risk” types of the human papillomavirus (HPV). Screening for cervical cancer using HPV is much more effective than the Pap test. However, HPV screening alone cannot determine if an HPV infection will resolve, or if it will progress to cervical cancer. We need to find better ways to identify the people with HPV who have the highest risk of cancer.
The microbiome of the vagina may play an important role in progression to cancer. Understanding more about the vaginal microbiome in those with high-risk HPV could help us determine when an HPV infection may resolve or when it may progress. This knowledge could lead to earlier and better treatment and prevent cervical cancer from developing.
This research will be done in British Columbia, Canada. We will determine the microbiome characteristics of an existing set of cervical samples. We will then link these characteristics to over 10 years of cervical cancer screening results. We will explore if certain microbiome characteristics can determine whether HPV progresses to cervical pre-cancer or if HPV will clear. These findings can lead to important advancements in HPV screening for cervical cancer. This study has strong potential to impact global cervical cancer prevention and treatment standards. The findings are especially important as screening programs around the world shift to HPV-based cervical cancer screening.
This research aims to improve cancer treatment, specifically immunotherapy. My lab will identify factors that determine patients’ immunotherapy responses. We already know that microbes in our gut impact cancer treatment. For example, research shows that a fecal microbiota transplant can overcome immunotherapy resistance. At first, our goal was to identify which microbes impact immune responses. However, a difficulty for this research was that the regions we live in change which types of microbes are in our gut. This is a problem because it makes it hard to validate findings between regions. Our work revealed that it is not the species of microbe that impacts immunotherapy responses, as we first thought. Instead, it is the types of proteins produced by these microbes that matter. Different species of bacteria can make similar proteins, and it is these proteins that drive immune responses. We developed a new strategy to identify the proteins that bacteria are producing in the gut. Our approach reveals a relationship between proteins and treatment response. We verified this relationship in melanoma patients from different regions. For our next steps, we propose identifying non-invasive immunotherapy biomarkers. We will do this with the fecal microbiome. We expect that our research will improve clinical decisions and treatment outcomes.
Pancreatic cancer is one of the deadliest cancers because it is very difficult to treat. There are only a few treatment options available, and they do not work very well for most patients. We propose to find new therapies by studying how certain molecules, called RNA-binding proteins (RBPs), contribute to pancreatic cancer growth. RBPs are important because they control how genes are translated into proteins and ensure that the right genes are expressed at the right time and in the right amounts. When they are not working properly, RBPs can contribute to cancer development. For example, how much of an RBP is made can be affected by certain changes in the cancer cells, like how genes are turned on and off. Additionally, how an RBP works can be affected by cancer-specific modifications to its protein structure. Our research will focus on understanding what goes wrong with RBPs in cancer and how we can fix it. We will determine which RBPs and which cancer-specific modifications of RBPs are important for tumor growth and drug resistance. This will help us find answers that could lead to new therapies for pancreatic cancer patients.
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