Eleven inspired projects underway with Knight Cancer pilot funds

Exploring immune therapy combinations to stop aggressive breast cancers. Unraveling the gene changes that make juvenile myelomonocytic leukemia so difficult-to-treat. Developing a biomarker to guide therapy against a deadly brain cancer. These are some of the ideas researchers are pursuing with the latest round of Knight Cancer Institute pilot project awards.

Up to $50,000 each, the awards help investigators generate the preliminary data needed to seek full funding from sources such as the National Institutes of Health. The awards are supported by the Betty Hise Foundation, the Hillcrest Committee, anonymous donations and the Knight Cancer Institute’s NCI Cancer Center Support Grant.

Andrew Adey, Ph.D., with Lisa Coussens, Ph.D.

Epigenetic tumor microenvironment reprograming in triple negative breast cancer

Triple-negative breast cancer is an aggressive subtype with a high risk of metastasis. Adey and Coussens are investigating how a novel combination of immune therapies, along with chemotherapy, impacts gene expression in immune cells present in mammary cancers. The aim is to uncover new targets for therapy, and biomarkers to stratify patients with triple-negative breast cancer for more effective treatment strategies.

Monika Davare, Ph.D.

Validating the oncogenic role and targetability of ROS1 in primary glioma model systems

Davare’s lab recently found that fusions of the ROS1 gene are found in child and adult patients with glioblastoma. In animal models of this lethal brain cancer, ROS1-targeted drugs reduce tumor size and prolong life. Davare’s project aims to test whether the overproduction of ROS1 in glioblastoma is a useful biomarker for potential therapeutic benefit of these drugs. The findings could facilitate new clinical trials for ROS1-positive glioblastoma patients.

Lara Davis, M.D.

Resistance training to improve physical function in sarcoma survivors

Sarcoma treatment leads to high rates of physical function limitations among survivors, but there are no evidence-based strategies to improve physical performance in sarcoma survivors. Davis’s project will gather meaningful, quantifiable data within a reasonable timeframe to address whether or not tailored progressive resistance training is feasible in survivors of sarcoma.

Summer Gibbs, Ph.D., with Jessica Riesterer, Ph.D.

Novel electrochemiluminescent probes for correlative light and electron microscopy (CLEM)

CLEM presents significant challenges for imaging in biological samples. Gibbs aims to develop electrofluorescent probes that are activated when an electron beam interacts with the sample. The generated photons can be collected simultaneously with electron microscopy images via a cathodoluminescence detector attached to a scanning EM. Initial development will be conducted using cell cultures and mouse models that exhibit interesting cancer biomarkers.

Amanda Lund, Ph.D.

Interrogating macrophage/lymphatic vessel crosstalk in melanoma

Lund’s lab has shown that lymphatic vessels play an active role in anti-tumor immunity and inflammation. Her project is exploring the contribution of a myeloid-biased, immunosuppressive microenvironment on lymphatic vessel function as it relates to the trafficking of dendritic cells and subsequent activation of anti-tumor immune responses in draining lymph nodes. The goal is to find new targets for stopping melanoma.

Julia Maxson, Ph.D.

Mechanisms underlying poor prognosis in setbp1-mutated juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia is an aggressive cancer mostly affecting young children. Five-year survival is about 50 percent. Maxson is pioneering new techniques to understand how the gene SETBP1 makes these cancers more aggressive and difficult-to-treat. Her project also aims to develop a mouse model of SETBP1-mutated JMML for mechanistic studies and potential drug development efforts.

Tomi Mori, Ph.D., M.B.A.

Impact of pregnancy-related factors on distant metastasis-free survival and tumor characteristics in young women with breast cancer

Breast cancers diagnosed within ten years after a woman gives birth are more likely to spread and become life-threatening. Mori and colleagues are using the Utah Population Database to clarify the links between pregnancy-related factors and breast cancer stage and molecular subtype. The goal is advance risk stratification for young women with breast cancer, aid the development of decision-support models, and advance the development of a chemoprevention trial to address an unmet need.

Naoki Oshimori, Ph.D.

A potential determinant of high-risk tumor development

The Oshimori lab has identified a gene strongly associated with survival in early-stage squamous cell carcinomas. Oshimori’s pilot project is exploring the role of this gene in the rearrangement of the basement membrane. The work aims to identify the key determinants of tumor progression that will make it possible to distinguish high-risk from low-risk squamous cell carcinomas, and enable the development of new strategies for cancer detection and treatment.

Jennifer Saultz, D.O.

Innate immune evasion of acute myeloid leukemia and therapeutic targeting

Saultz and colleagues have found that high levels of immature natural killer cells in the bone marrow of AML patients correlate with decreased overall survival. Her pilot project seeks to understand the innate immune profile changes associated with leukemic stem cell survival in the bone marrow through a detailed examination of RNA expression profiles in natural killer cells. The goal is to identifying novel immune therapies for AML.

Philip Stork, M.D.

Measuring glycolysis and lactate production microscopically within single cancer cells

Cancer cells alter their metabolic programs in a process called the Warburg effect. But whether the Warburg effect is the cause or the result of increased proliferation is not known. Currently there is no way to monitor this metabolic switch within single cells and a successful conclusion of Stork’s project will provide a novel tool to monitor metabolic programming within individual cancer cells during their evolution and treatment.

Kerri Winters-Stone, Ph.D.

Piloting a novel therapeutic intervention to restore health and functioning in cancer survivors with chemotherapy-induced peripheral neuropathy

Cancer survivors treated with chemotherapy often suffer from chemotherapy-induced peripheral neuropathy many years past diagnosis. Poor mobility and pain can make it difficult to engage in exercise to improve symptoms. Winters-Stone is testing the use of whole body vibration, a relatively new therapeutic modality for older adult and chronically ill populations that are unable to participate in rigorous exercise.