V Scholar Archives - Page 5 of 60

Esther Rheinbay, PhD

Uveal (ocular) melanoma (UM) is a rare type of eye cancer. When the cancer spreads to other sites in the body, outcomes are often poor. Unlike skin melanoma, UM does not respond well to new types of therapy focused on the immune system. Better treatments are urgently needed. Our lab has recently shown that UM tumors frequently lose a sex chromosome (Y in tumors from men, X in tumors from women). Loss of the male Y chromosome (LOY) in men and loss of one X chromosome (LOX) in women occurs in about half of tumors, thereby affecting many patients. We found that LOY is linked to worse survival, and that LOY and LOX can give clues whether a patient’s tumor will spread to other sites in the body. I now propose to study the exact role of LOY in UM with a combined approach. Using genome analysis, gene knock-outs and drug screens in uveal melanoma models, our team hopes to find the weaknesses of UM tumors with LOY. These weaknesses could suggest new treatments for patients. LOY is not limited to UM but also occurs frequently in other tumor types. Therefore, the proposed work has far-reaching implications for finding better treatments for many people living with cancer.

Jessica Stark, PhD

The immune system is your body’s resident doctor. Immune cells constantly examine the organs and tissues in your body. Most of the time, immune cells eliminate damaged or infected cells before they can make you sick. However, this process goes wrong in cancer. We now know that tumors use multiple strategies to hide from immune cells so that they can grow and spread throughout the body.

A new kind of medicine, called immunotherapy, teaches the immune system to recognize and destroy cancer. Some patients treated with immunotherapy cleared their tumors and remained in remission for decades – the closest we’ve come to a cancer cure. However, most patients with colorectal cancer, the second deadliest cancer in the US, do not benefit from existing immunotherapies. It is thought that these patients’ cancers have developed different or additional strategies to hide from immune cells – but how?

One way that immune cells examine cancer cells is by detecting the sugars, or glycans, they display on their surfaces. It was recently discovered that colorectal tumors decorate their surfaces with sugars that trick the immune system into thinking the tumor cells are healthy cells. Thus, glycans are emerging as a main strategy used by colorectal cancers to evade the immune system. This project will develop medicines that target these glycans as a new kind of immunotherapy. Our hope is that medicines targeting sugars can help improve outcomes for all patients with colorectal cancer.

Carla Nowosad, PhD

Immune cells are always patrolling our intestines, even when we are healthy. This includes B cells, which produce antibodies. Antibodies are floating molecular fire extinguishers which bind to and neutralize infections. In our intestines, huge amounts of antibodies are made every day. These bind to the ‘friendly’ bacteria that we live with to make sure they are well balanced, which keeps us healthy. In inflammatory bowel disease (IBD), the intestine becomes damaged by the immune system and antibodies change which bacteria they bind to. This turns the population of gut-bacteria from friendly to harmful, and can cause IBD to become colorectal cancer.

We do not know which B cells make cancer antibodies, or how antibodies make bacteria harmful. To understand this, we need to know how dangerous B cells become selected to produce the antibodies that turn IBD into cancer. This requires special tools to tell the helpful cells apart from the harmful ones. We built mice with multicolored B cells so we can follow the B cells that become hijacked during IBD and cancer. We may then understand where cancer-causing antibodies are made, and what they bind to. By doing this, we hope to compile a list of common antibodies that are always made before IBD becomes cancer, and look for them as warning signs in IBD patients. This could give doctors more time to treat high-risk patients before tumors form. In the future, we hope our findings help design new cancer drugs to delete harmful B cells.

Christine Eyler, MD, PhD

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.

Melissa Reeves, PhD

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.

Caroline Bartman, PhD

Funded with support from Hockey Fights Cancer powered by the V Foundation presented by AstraZeneca

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.

Xueqiu (Chu) Lin, PhD

Funded with support from Steve and Tamar Goodfellow

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.

Noam Auslander, PhD

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.

Corina Antal, PhD

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.

Shiri Gur-Cohen, PhD

Funded with support from the Michael Toshio Cure for Cancer Foundation

When a patient is diagnosed with cancer, they start treatment hoping to get rid of the unhealthy cells. But some cancers, including a common and aggressive type called squamous cell carcinoma, have an unsettling ability to resist treatment. When cancer cells escape therapy, patients may find that the tumor comes back after initially going away and that it starts to spread. Drug resistance is the main reason that cancers have been so difficult to eliminate. We know that genetic changes in healthy cells can cause cancer to form, but these don’t tell us why some cancer patients don’t respond well to treatment. My lab is developing new ways to observe how the surrounding healthy tumor environment is helping cancer cells resist therapy. We found that drug-resistant tumor cells rely on their connections with lymphatic vessels, typically considered as the waste drains of the body. Using a model of skin cancer, we are proposing a new tool to track cancer cells in their natural habitat to find how lymphatic vessels shield and protect the cancer cells. By targeting the supportive lymphatic network, we hope to prevent cancer cells from surviving therapy. We believe that our findings will lead to new ways to treat cancers and eliminating cancer relapse as a treatment fallout.