V Scholar Archives - Page 17 of 60

Shin-Heng Chiou, PhD

Funded by the Constellation Gold Network Distributors

Pancreatic cancer is one of the deadliest cancer types in the world. Most pancreatic cancer patients already develop advanced disease and are not suitable for surgery. A very small number of patients can live longer than ten years after surgery and are referred to as long-term survivors. Recently, unique bacteria were found in tumors from long-term survivors but not patients with shorter survival. In addition, long-term survivors tend to have higher numbers of T cells in their tumors – a cell type that is central to the immune system. Therefore, T cells might induce more powerful immune responses against cancer in long-term survivors through these unique bacteria. More precisely, we think that T cells in long-term survivors might “see” antigens from the bacteria and at the same time similar antigens from cancer cells. Our study is designed to understand the T cell responses unique to long-term survivors through T cell specificity inferences with our computer algorithms. The specificity inference will further guide our effort in finding these antigens that are “seen” by T cells in long-term survivors. Identifying these antigens from both cancer cells and the unique bacteria in long-term survivors will help us invent new and better treatments for pancreatic cancer patients.

Aadel Chaudhuri, MD, PhD

Cancer is a major cause of death worldwide. Immunotherapy is one of the most promising new ways to treat advanced stages of cancer. It works by “taking the breaks” off the immune system to let immune cells kill cancer cells better. Immunotherapy has revolutionized the treatment of cancers like melanoma, lung cancer and bladder cancer. Still, many patients do not respond to treatment. It is hard to know early who will respond and who won’t. We are developing and testing a method to predict response to immunotherapy early. We are doing this through a simple blood test that measures signal from immune cells deep inside a patient’s tumor. We are testing our method in melanoma patients. If successful, our method will revolutionize the ability to predict cancer response to immunotherapy. This will give doctors vital information early and improve patient survival.

Abhishek Chakraborty, PhD

Kidney cancer is among the ten most common forms of human cancer. While manageable in early stages, advanced kidney cancer remains incurable. Therefore, new drugs to treat this disease are urgently required.

Kidney cancers emerge when normal kidney cells acquire changes in their genetic program. DNA, our primary genetic source-code, is like a thread that is compactly wrapped into a complex spool called “chromatin”. This wrapping protects DNA from environmental adversity and also allows precise control to switch genes on/off, when desired. Importantly, many of the kidney cancer-causing genetic changes promote improper “chromatin” spooling, which possibly drives cancer growth by switching on the function of key tumor-promoting (onco)genes. Identifying and shutting off these misfiring oncogenes could thus block tumor growth, and be a means of therapy.

Our laboratory has begun comprehensively probing this idea. Using cutting-edge technology, we first identified numerous genes that were associated with improper “chromatin” spooling and thus were erroneously switched on in cancerous kidney cells. Among these genes, our follow-up studies shortlisted ten candidate oncogenes that promoted tumor growth in mouse models. Many of these gene products rewire the cancer cell’s metabolism. Here, we address which of these metabolic functions are indispensable for kidney cancer and how these changes fuel cancer growth. Cancer cells are perpetually hungry for nutrients to support their uncontrollable growth; therefore, starving kidney cancer cells of essential nutrients can be exploited for therapy. Together, our studies lay the foundations to establish such metabolic genes as clinically useful targets to treat kidney cancer.

Mariana Byndloss, DVM, PhD

Funded through the Stuart Scott Memorial Cancer Research Fund by John and Michele Truchard in honor of Jo Ann Truchard

Colorectal cancer is the second most common cause of cancer-related death in the United States. New research shows that colorectal cancer cases are increasing in younger age groups. We know that obesity is a major risk factor for colorectal cancer rates among younger adults, but we still don’t understand exactly how it works. Our research goal is to answer this important question. Obesity is mostly caused by unhealthy eating habits, including eating a diet rich in “bad fats”. First, we want to understand how healthy cells are damaged by “bad fats”. This is important because damages cells can produce harmful substances that cause cancer. “Bad fats” may also produce substances that feed harmful bacteria living in our intestines. These bacteria produce toxins that cause cancer. We will try to understand how the bad bacteria use this “food” to grow in the gut of obese individuals. This will help us show that “bad fats” cause cancer both by damaging cells and by feeding cancer-causing bacteria. If successful, our work will show how the dietary habits that lead to obesity can also cause colorectal cancer by damaging cells and feeding the growth of harmful bacteria. These findings will help us find new treatments for patients suffering from cancers caused by obesity.

Zuzana Tothova, M.D., Ph.D.

Abeloff V Scholar* (Tied for Top Rank)

Funded by the Constellation Gold Network Distributors

Use of a new DNA sequencing technology called next generation sequencing (NGS) has significantly improved our ability to describe the genetic basis of human cancers, including blood cancers like leukemia. However, we do not fully understand how most of the genes that cause leukemia play a role in this disease and how to target them with therapy. We know that mutations in a protein complex called the cohesin complex, which normally helps genes turn on and off, frequently occur in patients with blood cancers. These mutations usually occur during the process of disease progression from pre-cancerous states to highly aggressive cancer types. Cohesin mutations are found in 10-20% of patients with blood cancers such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) and are associated with poor survival. With this grant, we will focus on exploring how DNA changes mediated by the cohesin complex play a role in disease progression. Specifically, we will examine folding of DNA into loops and organization of chromatin during the steps of disease progression. Treatment options for patients with blood cancers are limited, and by expanding our understanding of the mechanisms by which leukemia causing genes contribute to disease development, we aim to inform the design of urgently needed therapies for patients. The impact of this work is far reaching and may extend to patients with other blood cancers, including chronic myelomonocytic leukemia (CMML) and chronic myeloid leukemia (CML), as well as patients with bladder cancer, glioblastoma, Ewing sarcoma and breast cancer.

Jihye Yun, Ph.D.

Colon cancer is the second leading cause of cancer-related deaths in the United States. An increasing number of human studies have highlighted the association among the consumption of sugary drinks, obesity, and the risk of colon cancer. It is currently thought that sugar is harmful to our health mainly because consuming too much can lead to obesity. It is well known that obesity increases the risk of many types of cancer, including colon cancer. However, whether a direct, causal link exists between sugar consumption and colon cancer has remained unknown.

Our group recently showed that consuming a modest amount of refined sugar every day—the equivalent of a human drinking about 12 ounces of a sugar-sweetened beverage daily—accelerates colon tumor development in mice, and it does so independently of causing obesity. The proposed project will identify the molecular mechanisms by which sugar enhance colon tumor development. In particular, we will focus on how sugary drinks alter the bacteria living in the gut and how these altered gut bacteria contribute to tumor development. To this end, we hope to identify bacteria that increase specifically in response to sugar consumption that could serve as new targets for prevention and treatment for colon cancer patients. Given that more than half of American young adults consume at least one sugar-sweetened beverage daily, and that young-onset colon cancer is on the rise for unknown reasons, any positive findings from this project will be of immense significance.

Vivian Weiss, M.D., Ph.D.

Funded by the Tyler Trent Fund and the Dick Vitale Pediatric Cancer Research Fund

A critical failure in the field of pediatric thyroid cancer care is the use of adult treatments for a childhood disease that has distinct genetics and tumor behavior. With thyroid cancer incidence rapidly increasing, we need to develop personalized treatments for this population to ensure their long and productive lives. There is currently no way to predict which children will go on to develop recurrent or aggressive disease at the time of biopsy and thyroid surgery. While thyroid cancer is generally curable, adolescents and young adults present with more frequent local and metastatic disease when compared to older adults. Adult treatment protocols lead to high cure rates, but adolescents and young adults have many years of potential recurrence, radioactivity-induced side effects, and secondary malignancies ahead. Precision medicine is becoming the standard of care for many diseases except pediatric thyroid cancer.

To develop more individualized pediatric thyroid cancer care, the scientific community must first strive to better understand the mutations and abnormal cellular signaling responsible for thyroid cancer behavior. Our research program utilizes a large cohort of adolescent and young adult human thyroid tumors in order to study the signaling pathways responsible for the unique growth and spread of each tumor. The funds from the Pediatric Cancer V Scholar Award will lead to an improved understanding of thyroid cancer development in this population and innovative therapies for children with this disease. These treatment strategies can then be applied to a wide range of pediatric cancers with reliance on similar signaling pathways.

Tuomas Tammela, M.D., Ph.D.

Lung cancer is the leading cause of cancer-related death worldwide, killing more than breast, prostate, colon, kidney, and liver cancer combined. Lung adenocarcinoma (LUAD), the most common type of lung cancer, alone kills ~60,000 Americans every year. Therefore, preventing lung cancer would have a large impact on society. Preventing lung cancer altogether would also address the problem of worse outcomes for patients who, for social and economic reasons, have unequal access to cutting-edge cancer treatment. Even patients who are cured of cancer experience psychological trauma, so prevention would also mean that no one would have to go through such a traumatic experience. Our initial results show that early lung cancers are less complex and therefore should be easier to eliminate compared to advanced disease that has spread from the lung to other parts of the body. We propose to study the earliest steps, when a normal lung cell becomes a cancer cell. To do this, we have developed a way to study lung cancer cells in the lab that closely resembles how tumors grow in humans. In addition to studying features of early lung tumor cells, we will also study the surroundings of these cells, a method that has not been used before to study lung cancer. We aim to discover molecular processes that are essential for the formation of lung cancer. Drugs could then be developed to block these processes and stop lung cancer at its earliest stages – preventing the disease altogether.

David Soto-Pantoja, Ph.D.

Funded by the Stuart Scott Memorial Cancer Research Fund

Our immune system operates on a balance of cells that can destroy infected or cancerous tissue and cells that prevent attacking healthy tissue. This balance is affected during cancer where cells that attack the tumor become inactivated. This allows further growth, cancer spread (metastasis) and eventual death of the patient. To address this problem researchers have developed drugs known as immune checkpoint inhibitors. These drugs activate T cells, a type of immune cell, to attack the tumor. Cancer patients treated with these drugs have seen major increases in survival. However, due to these drugs tipping the balance to a more active immune system, it can cause harmful side effects. These side effects cause interruptions in treatment plans which can result in disease progression. Currently, we do not have tests in the clinic that are able to predict these side effects. Therefore, there is an urgent need to understand how these side effects develop. Cancer cells consume abnormal levels of nutrients and release factors that can be sensed by blood circulating cells. We believe that these changes can be sensed by mitochondria. The mitochondria are organelles in cells that regulates energy metabolism. With new technological advancements, we can measure how this organelle changes in function in patients’ blood cells. We propose to test how patient blood cells energy changes. We predict that patients that develop side effects will have a lower cellular energy levels. Our study will provide a marker to predict side effects before they develop. We will also study genes that regulate cell energy metabolism to identify drug targets aimed at reducing the onset of side effects. Therefore, our studies will provide a personalized approach to cancer treatment to improve outcomes while preserving their quality of life.

Zachary Schug, Ph.D.

Funded by Hooters of America, LLC

The Schug laboratory is interested in understanding the way a cancer feeds itself in order to support its growth. The amounts and types of foods that cancers consume can be very different from the ones that our bodies normally use. For this reason, we believe that these differences can be used as new targeted treatment options for cancer patients. We have identified a specific food that is uniquely used by cancers to fuel their growth. Our goal is to create drugs that can block cancer’s ability to feed on this food. In addition, we are exploring the idea of combining this drug with other available treatments to improve patient survival. This research is important because it looks to block behaviors that are unique to cancer and therefore spares the body from harmful side effects. Furthermore, our results suggest that this food source is used by nearly all types of cancer. Because of this, we believe that our research is likely to make a major impact on the lives of many different cancer patients.