V Scholar Archives - Page 12 of 60

Maria Mihaylova, PhD

Colorectal cancer is the second leading cause of cancer related deaths worldwide. Alarmingly, recent studies show that its incidence is increasing in younger adults. Certain environmental factors, such as diet, can have an impact on colorectal cancer. Calorie dense, western diets can lead to energy imbalance and excessive weight gain, which is associated with higher risk of colorectal cancer. Since diet is a modifiable risk factor, it is important to understand precisely how diet composition and particular nutrients within the diet can affect colon tumor cells directly and indirectly. We plan to systematically examine how colon cancer cells become dependent on certain nutrients that are necessary for rapid tumor growth and progression. We will also test how relevant dietary nutrients, such as sugars and fats, change the function of support cells found within the tumor and influence tumor growth. Our hope is to identify vulnerabilities in colon cancer cells that we can enhance through nutrition and develop new treatments that will improve survival and quality of life for cancer patients.

Liron Bar-Peled, PhD

The goal of this project is to make new drugs against ovarian cancer genes using a new drug discovery method.  Ovarian cancer (OC) remains a deadly disease. OC will be diagnosed in over 21,000 women in the United States this year and 13,770 patients are expected to pass away during this time.  While initial responses to the best anti-cancer drugs are frequent, most patients with OC will experience disease again after 24 months of treatment, and most women will unfortunately pass away from this disease within five years. Thus, there is an urgent need to make new drugs to treat ovarian cancer. The classic approach to drug discovery is both time intense and costly, and most cancer drug discovery is focused on making drugs against cancer proteins whose shape is considered readily ‘druggable’. Our central premise is that many ovarian cancer proteins can be drugged. To test our idea, we will use a new tool that finds druggable proteins by detecting drug binding to cancer causing proteins in OC cell lines and patient tumors. If successful, this program should develop a new class of anti-cancer drugs to help women suffering from OC.

Nausica Arnoult, PhD

Fighting cancer is like a game a chess: each treatment can be followed by the adaptation of the tumor. Our next move requires the development of a novel treatment strategy. This is however a difficult task.

My research goal is to develop novel strategies to treat breast and ovarian cancers that are resistant to common drugs. Many breast and ovarian cancers are no longer capable to correctly repair DNA when it is broken. This Achille’s heel can be used to eliminate cancer cells without damaging healthy tissues. My research team has identified a novel protein that help repair DNA and that is essential in these cancers. Our goal is to develop a drug against this protein and to test if we can use it to kill certain cancers that became resistant to current treatments.

Alison Taylor, PhD

Funded by the Constellation Gold Network Distributors

Genetic information is carried in DNA, which is present in every cell of our bodies. Most cells have 46 chromosomes, which carry DNA within the cell. However, more than 90% of tumors have cells without the correct number of chromosomes. These cells are called “aneuploid”. Some whole chromosomes or large chromosome fragments may be duplicated or lost. Aneuploidy is a contributing factor in cancer formation. However, its exact role in this process is an unanswered question in cancer biology. The goal of this research is to understand the effects of different changes in chromosome number.

For our studies, we make use of a new technology that allows us to cut chromosomes at specific locations. With these experiments, we can study the effects of changes in large chromosome segments. Our current focus is a type of cancer called squamous cell carcinoma (SCC). In this cancer type, large pieces of chromosome 3 are affected. Here, we will uncover the interaction between chromosome 3 changes and DNA mutations. We will also create a human cell model of SCC. These studies address a gap in our understanding of aneuploidy in cancer by studying the effects of specific sets of chromosomal changes. With knowledge of how these chromosomal changes contribute to cancer formation, we will uncover new ways that cells can become cancerous. A better understanding of paths to disease formation will be crucial for designing new cancer treatments.

Christopher Seet, MD PhD

Harnessing the immune system to eliminate tumor cells has led to remarkable responses in several advanced cancer types. T cells are the key immune cell type which are engineered in the lab to seek out and destroy tumor cells, however in many cases tumor cells adapt to evade T cell killing, leading to disease relapses. Advances in cell engineering now permit T cells to be made in the lab from specialized stem cells. This technology promises to provide more cancer patients access to T cell therapies, but also presents the opportunity to make T cells more effective in prevent tumor escape. The goal of this research project is to study the ways in which tumor cells evade killing by lab-grown T cells, and how engineering specific molecules on lab-grown T cells may enable us to turn on tumor killing mechanisms to prevent tumor cell escape. Our overall goal is to further the development of this new kind of T cell therapy to be more effective across a wider range of cancer patients.

Siddhartha Mitra, PhD

Funded by the Constellation Gold Network Distributors in honor of the Dick Vitale Pediatric Cancer Research Fund

Brain cancers have recently surpassed blood cancers as the most common cause of cancer-related death in children. The big question we ask here is how we can make cancers easy to destroy from the inside by the body’s own soldiers. Modern cancer-treating drugs utilize the body’s defense mechanism to destroy tumors and have shown promising results against several cancers. However, most of these drugs have been developed against adult tumors and do not always behave similarly against childhood cancers. Furthermore, a lack of suitable targets that can differentiate childhood brain cancers from normal cells prevents the safe treatment of childhood cancers. This is more so due to our lack of understanding by which cancer cells hide from the body’s soldiers, especially in brain cancer.  While significant progress has been made in the care of children with medulloblastoma, some of those patients still suffer a lot. The cells create a signal on their surface which identifies healthy cells from diseased cells. It tells a particular type of cell called macrophages not to eat these cells. Macro meaning big and phages meaning eater mean Big Eater. The body uses some proteins to protect cells that should remain and help dispose of diseased cells. Cancers use this to create a force field to protect themselves. In this grant we will test how to reduce this force field on the surface so we can use the bodies soldiers to eat up the tumor.

Liling Wan, PhD

Acute myeloid leukemia is the deadliest blood cancer. The mainstay chemotherapeutic treatments have met with limited success, and most patients will die from their disease. Thus, New treatments are desperately needed. To address this need, we have identified a cellular pathway leukemia cells rely on to live. In this project, we have developed an inhibitor that blocks this pathway and found that it kills leukemia grown in mice. We would like to understand why some leukemia cells rely on this pathway to survive and what determines the response to the inhibitor. If successful, our work will provide preclinical evidence for a new pathway as a target for acute myeloid leukemia and offer needed knowledge and chemical tools to guide future clinical studies. We are hopeful that our findings could lead to improvements in the lives of AML patients.

Anastasia Tikhonova, PhD

Immunotherapy is a type of cancer treatment that uses the body’s own immune system to fight and destroy cancer cells. Despite its success in treating a number of cancers, immunotherapy has had a limited impact on the treatment of blood cancers, known as leukemia. While there are many reasons for this, a primary reason is the current lack of understanding of how the cells of the immune system interact with leukemia cells. Present knowledge of the types of immune cells that live in the bone marrow and their behavior at various stages of leukemia are almost entirely lacking. To address this, we will perform a widespread analysis of immune cell composition and function during leukemia disease progression. We will use cutting-edge technology to understand the biological mechanisms that become altered during leukemia, which may cause immune cells to promote the cancer’s initiation and relapse. These studies would enable the identification of “immune signatures” associated with different stages of cancer development. The findings will lay the groundwork for our understanding of the bone marrow immune landscape in the context of the human disease. We envision that these studies will fundamentally lead to new treatment strategies for this devastating cancer and thereby improve patient outcomes.

Andrew Roth, PhD

Vintner Grant funded by the V Foundation Wine Celebration in honor of Rich and Leslie Frank and in memory of Edythe Frank

When a patient is diagnosed with Follicular Lymphoma (FL) the effect the disease will have is unpredictable. Many patients will do well and live many years. But, some patients will have what are called transformation events.

Transformation is when a new, more aggressive type of lymphoma develops. When this happens patients do not do well. With no way to know which patients will transform, doctors cannot determine the best strategy for treatment. But even if they could predict transformation, it is not clear what the best course of action is since we do not understand the biology of transformation.

Recent research has shown that the non-cancerous cells in a tumor can have a major impact on how the tumor behaves.

These cells can create an environment that either encourages or limits tumor growth. The way cancerous and non- cancerous cells are organized can be thought of as the architecture of the tumor. By comparing the architecture of patients that do and do not transform, we believe that we can find better ways of predicting and preventing transformation. To do this we will employ cutting edge technologies that allow us to precisely measure features of thousands of single cells and look at how they are organized. We will use artificial intelligence to build a new approach to predict transformation using this information. This will also let us learn about the causes of transformation and how to prevent it.

Jihan Osborne, PhD

Funded by the KAAB Memorial Foundation and the Stuart Scott Memorial Cancer Research Fund

Cancer kills millions of people every year. The deadliest cancers are those that have high rates of metastasis. Metastasis is the movement of cancer cells from one organ site to another. Many of the current therapies are designed to kill cancer cells from the original tumor but not the secondary tumors that follow. We find genes responsible for normal embryonic development are improperly present in tumors but not in normal adult tissue. Many of these abnormally expressed genes control activities required for successful invasion and migration to distant organ sites. The purpose of the proposed research project is to comprehend how tumors use these embryonic genes to become metastatic and resistant to chemotherapy. This research will ultimately enable researchers to better target these aggressive gene programs, leading to increased patient survival and hopefully eradication of the metastases. My training as a cancer and developmental biologist puts me in a unique position to tackle these difficult questions. The medical community has finally realized that there will not be one treatment for cancer and each tumor is as unique as the individual is. Therefore, we must think outside the box to design therapies that target genes that responsible for growth, resistance to chemotherapy and metastasis. This current project seeks to understand why developmental pathways are re-expressed as well find ways to specifically target these pathways to inhibit metastasis.