Liver cancer is among the top four causes of cancer death. Historically, liver cancer is driven by HCV. Now, liver cancer is the fastest-growing cause of cancer death in the United States. This is due to the increase of nonalcoholic fatty liver disease (NAFLD), affecting around 25% of the global population. Emerging evidence defines over-nutrition environment and circadian misalignment as risk factors for NAFLD and liver cancer. So far, there is no FDA-approved drug to target the progression of NAFLD to liver cancer. Therapeutic approaches for liver cancer are also limited. Therefore, it is important to understand the mechanisms behind NAFLD-related liver cancer and identify new therapeutic targets.
We reported that a lipid-lowering drug decreased liver fat more when given in the afternoon than when given in the morning. This work is an example of chrono-pharmacology, where giving drugs at specific times of the day can maximize efficacy. My recent work revealed eating time as a key pacemaker for rhythmic metabolic processes in the liver. We can find a potential preventive approach for metabolic disorders and cancer patients by exploring this relationship between the internal clock and eating time. Chrono-nutrition is adjusting diet schedules to maximize results for treatment. The future project will identify how circadian rhythm affects liver cancer cells. These studies aim to find new targets of circadian physiology and reveal insights into liver cancer prevention and treatment.
Funded by the Stuart Scott Memorial Cancer Research Fund
Liver cancer is a leading cause of cancer-related deaths. Its incidence continues to increase, posing a significant threat to public health. A leading risk factor is the chronic exposure to liver stress, which, in turn, enhances the uncontrolled division of cancer cells and tumor growth. Proteins are the functional units within cells. They are made from the instructions stored in DNA and carried by messenger RNA (mRNA) through a process known as translation. Notably, the information stored in DNA is not static and can be modified to alter the outcome of translation to promote cancer growth. Two of these modifications are called ‘RNA oxidation’ and ‘RNA acetylation’, which are induced in liver cells in response to cellular stress, and their levels correlate with tumor growth. Thus, this study will investigate how the interplay between RNA modifications and translation promotes liver cancer. The results obtained in this study will allow for future clinical efforts to fight liver cancer.
Funded in partnership with Miami Dolphins Foundation
Liver cancer is deadly. Hepatocellular Carcinoma, or HCC, is the most common type of liver cancer. There are significant racial differences (disparities) in how long people with HCC survive. Black people with liver cancer do not live as long as White people. Also, Black patients are less likely to receive treatment. Previous studies have been unable to explain why these differences exist. We started a research study to learn about various factors that might contribute to these disparities. When we approach patients to participate, many say that they are too overwhelmed. Some patients do not understand what is happening when they are first diagnosed. In this study, we will ask patients and caregivers what needs we might be able to help with. We will also ask healthcare staff and patient advocates to identify what needs patients have. Together with patients, caregivers, advocates and medical staff, we will create a program that helps high-risk patients to navigate the health care system and provides extra support to the patients who need it most. This study is unique because we will train lay people to work as navigators, rather than nurses. By building a relationship between the patient and navigator, we will be better able to meet our patients’ needs. We expect this program to increase the number of patients that come to their appointments and get cancer treatment. This program may increase patients’ willingness to participate in research studies, which could dramatically improve our ability to understand and eliminate disparities in survival.
Funded in partnership with Miami Dolphins Foundation
Like computers, the cells that make up our bodies also have specialized ‘software’ that runs their specific functions. When cells in the blood become cancerous -known as leukemia-, they hijack this biological software. By doing this, the leukemia cells can grow very fast and quickly multiply. Despite the many different types of leukemia that exist, they all share certain defects in their biological software. We call these shared defects a ‘biological common denominator’ across all of them. As part of this biological common denominator of leukemia we have identified the abnormal loss of PDZD2. Although PDZD2 is a gene capable of stopping the growth of other types of cancers it has never been studied in leukemia. Normally, PDZD2 is present in healthy blood cells. However, when blood cells become malignant, they lose PDZD2. We will explore how loss of PDZD2 helps turn healthy blood cells into leukemia. Importantly, we will determine if treatment of cells with a synthetic version of PDZD2 can help stop the growth of leukemia cells. Our long-term goal is to develop a novel way to treat patients with leukemia. We expect that this synthetic PDZD2 will kill the leukemia cells while having no effect on healthy blood cells.
The Epidermal Growth Factor Receptor (EGFR) gene mutations can be detected in about 15% of patients with lung cancers. In female lung cancer patients who have never smoked cigarettes, as many as 50% of patients have this EGFR mutation. These mutations in the EGFR gene can be different from patient to patient, but all lead to the generation of an active protein that drives cells to survive, proliferate, and become cancerous. Currently, we have efficacious drugs for some of the EGFR mutations, but many other mutations do not have an approved drug. To address this unmet need, I am leading a clinical and translational research program including multiple clinical trials aiming to bring new approvals to treat those atypical EGFR mutations lung cancers. We will collect clinical information and bio-samples (both blood and tissue) to understand why some tumors respond to a certain drug, whereas other tumors not, to characterize the landscape of resistance mechanisms for each group of EGFR mutations. We will test a number of novel drug-drug combinations to overcome resistance and provide more potential options for EGFR mutation lung cancer patients. In this program, we will take a team approach to engage investigators with different expertise, use leading-edge technologies, including computational biochemical approaches and single-cell transcriptomics analysis, and ultimately nominate future therapeutic options for patients.
Pancreatic cancer is an awful disease that kills about 50,000 people a year and is going to be the second most common reason people die of cancer in 2025. We have few treatments for pancreatic cancer that do not work very well and can make patients sick. More treatments for pancreatic cancer that shrink the cancer tumors and do not make patients sick are needed now. Our studies have shown that combining two pills, trametinib and hydroxychloroquine, shrink pancreatic cancer tumors in mice, as well as, in a pancreatic cancer patient. In addition, our previous clinical trial has shown that this combination of pills is easier for patients to take and does not make them sick in a small number of patients. We would like to now see whether the combination of trametinib and hydroxychloroquine pills shrinks pancreatic cancer tumors and leads to a longer life in more pancreatic cancer patients. If our study is successful it might allow for a treatment for pancreatic cancer patients that will make them live longer lives and not cause them to become sick.
The cells in the human body are constantly subjected to stress, which is linked to changes in cellular metabolism. Our research team, and others, have made connections between these cell conditions and cancer. Our central question is: Can we make a simple blood test that provides an accurate measure of ongoing cell stress and metabolic changes to gauge an individual’s risk of cancer? This test may provide more than just a snapshot measure of cancer risk. For example, the test could be used to measure how lifestyle changes modify cancer risk across the lifespan. To answer our question, we developed expertise that enables rapid measurement of signals in certain blood cells attributed to changes in cell stress and metabolism. Our study will determine if these signals can be used to quantify cancer risk. We will obtain blood samples from individuals without cancer, from individuals who have a condition known to increase their risk of cancer, and from individuals diagnosed with cancer. We will isolate certain cells from these samples and then measure the candidate signals in the cells. We anticipate our studies to reveal that the signals we are measuring will be the lowest in healthy individuals, will increase in individuals with the precancer condition, and will be highest in people diagnosed with cancer. These findings would powerfully validate our technology and suggest that individuals may benefit from our test for the early detection, and even prevention, of cancer.
The study will detect cancer of the prostate in African-American men. African American men develop prostate cancer at a young age. The cancer spreads rapidly making it difficult to treat. Our method will detect substances produced by prostate cancer. The test will examine blood collected from men who have concerns with their prostate. The study will develop the test and make it available in the clinic. The test will help African American men in the community who do not have access to medical care. Early finding of prostate cancer will provide enough time for cure and will help reduce cancer related suffering and death.
Lung cancer is the leading cause of cancer death in both the US and the world. There is an effective screening tool called low dose computed tomography (CT) scans of the lungs, which can find lung cancers earlier while curative surgery is still an option. These screening CT scans are recommended once to year for heavy current and former smokers, but only a tiny fraction of those who should be getting lung screening are receiving it, in part because of the high false positive rate with screening CT scans. When lung screening identifies an abnormal area (called a nodule) within the lung, the chances are much greater that it will turn out to be benign rather than cancer. However, to prove the nodule is benign a battery of tests and procedures are often ordered, leading to cost, inconvenience, possible complications, and worry. Our project aims to cut the obstacle of false positive results on lung cancer screening in half by developing a blood test that can be drawn in a doctor’s office after a patient is found to have a lung nodule on a screening CT scan and can help predict whether the nodule is benign or cancerous. The test is built upon a cutting-edge technology called multiplexed mass spectrometry-based plasma proteomics, which can detect the signature spectrum of hundreds of proteins within a patient’s blood plasma using just a small sample. Our test will look at the pattern of proteins to see if the pattern matches those seen in cancer patients. Our long-term goal is to develop an accessible test that will promote increased lung cancer screening uptake and lead to more lives saved.
In cancer, many processes and functions of cells are changed. One such change is the presence of errors in the DNA sequence of cancer cells. By searching for these errors in blood samples from patients, one could use these as a means to detect the disease. In early disease, the presence of these errors in blood is scarce compared to normal cells, making their detection difficult. Recently, in addition to mutations, the DNA has also been observed to be chemically changed at an early stage. One such change (DNA Methylation) is vastly different in cancer cells and it covers larger regions of DNA, making it easier to detect. Analyzing these patterns from blood could be a viable means to detecting cancer in its early stages. In this proposal, we will map out the profile of patients who develop Acute Myeloid Leukemia (AML). We will use blood samples from a large number of patients that were diagnosed with the disease. Importantly, we have identified samples from patients who have particularly aggressive forms of the disease. Our objective is to create biomarkers to identify the disease early through blood samples, differentiate aggressive disease from benign ones. This allows us to treat lethal cancers with more aggressive therapy at an earlier stage. Together, we propose an exciting opportunity to detect cancer early and identify patients who could benefit from treatment before their cancer grows beyond control.
