Funded by the St. Louis Blues in support of Hockey Fights Cancer powered by the V Foundation
Therapies that modulate the immune response avoid the harmful side effects of standard cancer therapies and also have the potential to be more effective and longer-lasting. The most successful immune therapies to date rely on engineering a specific type of immune cells, T cells, to target and kill cancer cells. These therapies can be curative for some, but unfortunately still do not achieve their potential of cure for most. Our lab has identified a specific molecular pathway responsible for controlling the function of these immune cells. The goals of this project are to first understand how the driver of this pathway, a protein called BACH2, regulates engineered T cell function. Second, we aim to use advanced protein engineering tools to control the activity of BACH2, allowing us to thereby control engineered T cell function at will. If successful, these studies will shed light on a previously under-appreciated pathway that lies at the center of T cell function. Further, they will layout a pathway for “remote control” of BACH2 and nearly any T cell molecular program, allowing precision control of this potent anti-cancer therapy.
Funded by the Stuart Scott Memorial Cancer Research Fund
Pancreatic cancer is an extremely deadly disease, due to its ability to spread to other organs early and easily, a process known as metastasis. Molecules called purines are often used to build DNA and have been shown to be used by cancer cells to grow and survive. Pancreatic cancer usually spreads to the liver, an organ rich in purines. We find that pancreatic cancer cells, which contain mutations in certain genes involved in cell growth, prefer to use purines to uncontrollably grow and survive. Our study will identify how metastatic pancreatic cancer cells use purines to spread and survive in organs such as the liver. We will also test FDA-approved drugs used to treat other purine-dependent diseases such as gout and metastatic breast cancer to treat pancreatic cancer addiction to purines.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Immune checkpoint inhibitor therapy (ICT) is a form of cancer therapy that boosts the immune system to kill cancer cells. ICT can help cure some adult cancers but has not been effective in children with cancer. This proposal explores whether a combination of standard cancer therapy and ICT is both safe and effective in children with solid tumors in a clinical trial. First, we will test tumor, blood, and stool samples collected from patients in this clinical trial. We will attempt to learn what factors determine whether a patient will respond to this combination therapy or not respond. Second, we will use mouse cancer models to test different combinations of standard cancer therapy and ICT to see which combinations work the best. This work will help us understand if combining standard cancer treatments with ICT is both safe and effective in children with solid tumors.
Cancer cells often change their DNA to make more of the genes that help them grow and spread quickly. They do this with special proteins called transcription factors that read DNA, and helper proteins that change the DNA to work better. In prostate cancer cells, a protein called androgen receptor (AR) is the main cause of cancer growth. This is different from how AR works in normal prostate cells, where it helps the prostate develop properly and stops extra growth. We don’t know exactly how AR’s function changes in prostate cancer cells. My research tries to figure this out. With help from the V Foundation Award, my team will study a new protein called NSD2 that works with AR. Notably, NSD2 is only found in prostate cancer cells, not the normal ones. We’ll also test a new drug that stops NSD2 from working and see how well it kills cancer cells in different types of prostate cancer. This research will help us find more proteins that make AR cause cancer and create new medicines that target NSD2 to treat prostate cancer.
Funded by the Stuart Scott Memorial Cancer Research Fund with support from the Oral Cancer Cause
Voice is an incredible tool that we use every day to express our feelings and even our health. You can often tell if someone is stressed, happy, or not feeling well just by the way they sound. In fact, over 50 different diseases can cause noticeable changes in a person’s voice. One of the most serious conditions that affect the voice is laryngeal cancer, or cancer of the voice box. This type of cancer can cause major changes in a person’s voice, even in the early stages. Unfortunately, if it is not caught early, it can lead to the loss of voice, difficulty swallowing, and too many cases, death. The earlier we detect laryngeal cancer, the more treatment can preserve the voice and improve survival rates. The problem is that while many people with laryngeal cancer experience voice changes, most people who have a change in their voice do not have cancer. This creates a challenge for primary care doctors, who need to identify the rare instances where voice change suggests something more serious. To help with this, we are developing a machine learning tool that can listen to voice recordings and help doctors figure out when a patient may be at high risk for laryngeal cancer. This could help detect cancer earlier and save lives by making it easier for doctors to know when to refer patients to specialists for further testing.
Myeloma is a blood cancer that causes bone and kidney damage. Myeloma is the second most common blood cancer. New treatments are improving patient lives, but patients have to take medicine for the rest of their life. The cancer eventually adapts to these drugs and harms patients.
We will study myeloma that has become drug resistant. We are testing new therapies that can overcome drug resistance. This new therapy targets something called a co-activator. Co-activators turn on genes that enable the cancer to grow. Our research will treat cancer models with inhibitors of co-activator to understand how they work. We will also test different co-activator inhibitors to see which are most effective. Finally, we will look for genes that cause drug resistance. These studies will help guide ongoing clinical trials in myeloma. The long-term goal of this research is to find the right combination of therapies that will stop myeloma from growing.
Funded by the Stuart Scott Memorial Cancer Research Fund
Our research looks at how hormone receptors play a role in cancer. These receptors are involved in prostate, breast, uterine, and ovarian cancers. Normally, they help control important functions in the body. But as people get older and hormone levels drop, these receptors can stop working properly and help cancer grow.
Even though there are treatments that block these receptors, many patients still see their advanced cancers return within two years. This happens because cancer cells find new ways to turn the receptors back on, which makes the treatments less effective.
To tackle this problem, we use advanced imaging tools, including high powered microscopes, to make 3D models of the hormone receptors. This helps us see how the receptors work and what goes wrong in cancer. We have already found new interactions at the molecular level that were not known before. With support from the V Foundation, we hope to create better drugs that target these receptors more effectively, helping to stop cancer from coming back and improve patient outcomes.
Our bodies are constantly exposed to a multitude of challenges, such as microbes, toxins, and injuries, especially at barrier surfaces like the skin, lungs, and intestines. These tissues serve vital and complex functions in shielding us from environmental threats while also managing body moisture, oxygen levels, and nutrient absorption. For instance, the intestine must delicately balance the elimination of harmful microbes and toxins with the absorption of essential nutrients. This requires intricate cooperation between the intestinal lining cells and the intestinal immune system. Barrier tissues, like the intestine, are particularly prone to inflammation and cancer.
Inflammatory bowel diseases are chronic inflammatory conditions affecting the intestines. They result from an interplay of genetic and environmental factors, leading to dysregulated functioning of intestinal cells and immune system. These incurable diseases can significantly increase the risk of developing colon and rectal cancer. Yet, the mechanisms through which environmental factors and inflammation impact the immune system and cells of the intestine to drive the progression of chronic inflammatory diseases and cancer remain largely unknown.
Within the Niec lab, innovative tools have been developed to investigate how immune cells and the intestinal barrier cells respond to environmental challenges and interact in disease. Through this project, we aim to unravel the alterations occurring in the immune system and the intestine during inflammation. By understanding these processes, we aspire to develop strategies to prevent and treat cancer that arises from inflammatory bowel disease.
Cancer must change its nutrient uptake to grow. Drugs blocking cancer’s use of nutrients have been the basis of cancer therapy. However, most of these drugs work by blocking the pathways that metabolites use. They exhibit significant toxicity since they also harm normal tissues. We are looking at metabolite-targeted therapies that are less toxic. We hope the therapy will be more specific and effective as well. We don’t seek to block metabolite pathways. Instead, we target the specific metabolites that change in the tumor microenvironment. We study and harness the power of our body’s metabolites as drugs. Our work has the potential to change how we target cancer, leading to less toxic and more effective drugs. Our work will also help to diagnose cancer.
To understand how genes change in cancer, our field has uncovered many gene mutations and deletions in patient tumors. However, we have not yet been able to create treatments that can combat many of these changes. This research proposal will test the potential for new combinations of medicines to treat tumors with a common gene many cancers need on for survival, PRMT5. A number of aggressive tumor types have PRMT5 as a drug target including lung cancer which remains the leading cause of cancer-related deaths in the U.S. and pancreatic cancer where >90% of patients with this disease will succumb to it. We need to make better medicines to treat these cancers.
We will test our ability to drug PRMT5 protein in lung tumors in combination with other new drug targets. This work will provide fundamental insights into mechanisms of PRMT5 function and reveal new strategies to treat an aggressive and deadly form of cancer. It is necessary that we test and design effective, rationale combination therapies in cancer. These efforts aim to effectively kill tumors and to avoid tumors coming back in the patient.
This work could lead to clinical trials in the future that would directly benefit cancer patients and their families. My goal is for our laboratory to contribute to mentoring young scientists and to improving cancer treatment for patients. This V scholar award will help me to achieve my goals by providing additional support, mentorship, and scientific exchanges.
