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Siteman Investment Program awards $2.2 million in cancer research grants

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Washington University School of Medicine
Special guest comedian Dana Carvey at the Foundation for Barnes-Jewish Hospital’s annual Illumination Gala benefiting Siteman... Special guest comedian Dana Carvey at the Foundation for Barnes-Jewish Hospital’s annual Illumination Gala benefiting Siteman Cancer Center. This year's event raised a record-breaking $3 million for cancer research.

Research on breast cancer and the effects of chemotherapy are among the seven projects that will benefit from $2.2 million in new grants announced by Siteman Cancer Center through its Siteman Investment Program. The goal of the grants is to support and accelerate the pace of innovation in cancer research.

The money awarded comes from a variety of sources: Pedal the Cause annual bike challenge and Illumination gala, through the Cancer Frontier Fund at the Foundation for Barnes-Jewish Hospital; the Fashion Footwear Association of New York; the National Cancer Institute; and the Barnard Trust.

The research projects are described below.

Title: Siteman Cancer Center Breast Cancer SPORE

Principal investigator: William Gillanders, MD, a professor of surgery at Washington University School of Medicine and a research member of Siteman Cancer Center

Amount: $400,000 over one year

Goal: To create a Specialized Program of Research Excellence (SPORE) focused on tumor immunology, oncologic imaging, surgical oncology and breast cancer prevention that will enable researchers to quickly translate basic science discoveries to clinical uses for patients with breast cancer

Description: Breast cancer is a mixed and diverse disease that will require a combination of prevention, diagnostic and treatment approaches to decrease mortality. This project brings together a multidisciplinary team of investigators leveraging institutional strengths in basic and translational research. The objective is to obtain NCI funding for a Breast Specialized Program of Research Excellence (SPORE) that will enable rapid clinical translation of basic science discoveries with the goal of impacting patient care. Siteman Investment Program funds will provide critical continuing support for the development of a Breast Cancer SPORE at Siteman Cancer Center with a focus on tumor immunology, oncologic imaging, surgical oncology, and breast cancer prevention.

Title: RNA as a target of alkylation chemotherapy in cancer

Principal investigators: Nima Mosammaparast, MD, PhD, an assistant professor of pathology and immunology at the School of Medicine and a research member of Siteman Cancer Center, and Hani Zaher, PhD, an assistant professor of biology at Washington University School of Arts and Sciences

Amount: $400,000 over two years

Goal: To better understand the importance of chemotherapy-induced RNA damage of cells which will impact our understanding of how tumors respond to chemotherapy and ultimately may lead to new targets for chemosensitization

Description: Alkylating agents, a highly reactive group of molecules, are frequently used in cancer chemotherapeutics. These drugs are thought to work primarily by damaging the genome, which consists of DNA. However, another key molecule in the cell that is targeted by these drugs is RNA. Yet, we do not understand whether RNA damage by alkylating agents is important for tumor responses to these drugs. At a chemical level, RNA is very similar to DNA and changes to its structure often affect its function during protein synthesis. Therefore, we propose that RNA damage contributes to cell death upon exposure to alkylating agents. Our studies will focus on understanding how cells deal with RNA damaged with alkylating agents, and how this may affect tumor responses to these commonly used drugs. This work represents a major paradigm shift in our understanding of how tumor cells respond to chemotherapy, and may provide new ways of treating multiple types of cancer.

 

Title: Optimizing decision making about breast reconstruction after mastectomy: A patient-centered approach

Principal investigators: Siteman Cancer Center research members Terence Myckatyn, MD, a professor of surgery at the School of Medicine, and Mary Politi, PhD, an associate professor of surgery at the School of Medicine

Amount: $400,000 over two years

Goal: To develop a clinical decision support tool that will enable physicians and patients to make high-quality breast reconstruction decisions, ultimately improving cancer survivorship for women with breast cancer

Description: Deciding whether or not to have breast reconstruction after mastectomy, when to have reconstruction, and which type of reconstruction to have is very challenging for patients with breast cancer. Currently, this choice is limited by inadequate information and deficits in knowledge about treatment options. In this proposal, we aim to develop and evaluate a novel clinical decision support tool that integrates patients’ unique clinical characteristics with their preferences to enable clinicians and patients to make high-quality breast reconstruction decisions. This research will promote personalized cancer care for patients with breast cancer. Ultimately, this proposal has the potential to improve knowledge of treatment risks, harms and benefits; enable patients across racial groups to get the treatments they prefer; and improve outcomes patients find important, thereby improving cancer survivorship for women with breast cancer.

 

Title: Evaluating cognitive function and functional connectivity in breast cancer survivors who received chemotherapy

Principal investigators: Jay Piccirillo, MD, a professor of otolaryngology at the School of Medicine and a research member of Siteman Cancer Center; Lindsay Peterson, MD, an assistant professor of medicine at the School of Medicine; Alex Wong, PhD, an assistant professor of occupational therapy at the School of Medicine; and Bradley Schlaggar, MD, PhD, a professor of neurology at the School of Medicine

Amount: $400,000 over two years

Goal: To better understand the basis of chemotherapy-related cognitive impairment (CRCI) in breast cancer patients, to ultimately improve the survivorship experience

Description: Chemotherapy has been linked to cognitive impairments among breast cancer patients, especially related to planning, learning and attention. The neurological basis of this phenomenon, termed chemotherapy-related cognitive impairment (CRCI), is unknown, and the impact in patients over an extended period of time is lacking. The study aims to establish the groundwork to allow the assessment of the structural brain reasons that CRCI occurs and to evaluate why some patients develop CRCI and others do not. All newly diagnosed eligible breast cancer patients scheduled to undergo chemotherapy at Siteman Cancer Center will be enrolled in order to establish the Clinical Database for Cognitive Assessment. These patients will complete several cognitive function measures pre- and post-chemotherapy. A subset of these patients will complete special MRI functional imaging pre-and post-chemotherapy. Ultimately, the results of this project will support the exploration of the reasons why CRCI occurs and identify ways to improve the survivorship experience for breast cancer patients.

 

Title: A genetic model of perineural invasion

Principal investigator: James Skeath, PhD, a professor of genetics at the School of Medicine and a research member of Siteman Cancer Center

Amount: $200,000 over two years

Goal: To discover the molecular causes of cancer metastasis along nerves (perineural invasion) and better understand the molecular basis of this aggressive yet poorly understood form of metastasis

Description: Metastatic spread of tumors is often the key event that leads to cancer-related mortality. Although the blood and lymph systems represent the most common routes for tumor metastasis, nerves identify a key under-appreciated path for cancer spread. Perineural invasion is the process by which tumor cells migrate along nerves to invade distant tissues. First identified in the 1800s, perineural invasion is common in many cancers and a marker of poor outcome. Despite its clinical significance, the causes of perineural invasion remain unknown. We have developed one of the first in vivo model systems of perineural invasion. Here, we will exploit this system to uncover the molecular causes of perineural invasion. Given the lack of knowledge about perineural invasion, our research holds the potential to break open the field and catalyze advances in our understanding of this poorly understood form of cancer metastasis.

 

Title: Fatty liver promotes hepatic breast cancer metastasis

Principal investigator: Steven Teitelbaum, MD, the Messing Professor of Pathology and Immunology at the School of Medicine and a research member of Siteman Cancer Center

Amount: $200,000 over two years

Goal: To better understand the mechanisms by which fatty liver disease, a reversible and preventable disease, promotes breast cancer metastasis to the liver

Description: The United States is experiencing an epidemic of obesity which is often associated with fatty liver disease, estimated to be present in 20 percent to 30 percent of Americans. Surprisingly, nothing is known about the influence of fatty liver disease on liver metastasis. We find that whereas normal mice are resistant to liver metastasis of breast cancer, those with fatty liver are predisposed. This observation is important as fatty liver disease is reversible. We propose to determine why fatty liver predisposes to liver metastasis and if reducing liver fat prevents cancer spread. If our data extends to humans, it would have significant public health implications.

 

Title: Nonsense-mediated mRNA decay in DNA damage response

Principal investigator: Zhongsheng You, PhD, an associate professor of cell biology and physiology at the School of Medicine and a research member of Siteman Cancer Center

Amount: $200,000 over two years

Goal: To better understand the effects that DNA damage generated by radiation and chemotherapy has on the healthy cells surrounding the tumor, in order to develop new therapeutic strategies that will ultimately lessen side effects and cancer relapses.

Description: The mainstays of cancer treatment have been radiation and chemotherapy that generate DNA damage. However, the efficacy of DNA-damaging therapies is hampered by serious side effects and frequent cancer relapse. A major cause of cancer relapse is the alterations in gene expression that occur after treatment in the cells in the environment surrounding a tumor. Thus, it is imperative to understand the molecular mechanisms for the gene expression changes induced by DNA damage. The goal of this pre-R01 application is to explore the role of an RNA degradation pathway called nonsense-mediated mRNA decay in the reprogramming of gene expression in response to DNA damage. This project is expected to generate key experimental results that will enable development of new therapeutic strategies targeting harmful changes in the tumor environment.