Back to All News

Siteman Investment Program awards $2 million in cancer research grants

Cyclists prepare to begin the Pedal the Cause Classic route. (Pedal the Cause 2016). Cyclists prepare to begin the Pedal the Cause Classic route. (Pedal the Cause 2016).

Research on upper gastrointestinal cancers and recurrent glioblastoma are among the seven projects that will benefit from $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: Mechanisms of Gastrointestinal Adenocarcinoma Tumorigenesis

Principal investigator: Jason Mills, PhD, MD, a professor of medicine at Washington University School of Medicine and a research member of Siteman Cancer Center

Goal: To identify the genes that may start cancers in the stomach, intestines, liver and pancreas, to find drugs targeting those genes to stop cancer before it starts

Description: Cancers of the colon, liver, pancreas and stomach are among the most common and deadliest. Because these cancers first show pre-cancerous changes, such as intestinal polyps, preventing or even reversing these cancers may be possible if we understood how they begin. Researchers will study genes and cell-to-cell communication that breed pre-cancerous growths, then will look for therapeutic drugs that work with individual patients’ genes to block the onset of cancer.


Title: Post-XRT Effects in Brain Parenchyma Promote Dramatic Changes in Glioma Phenotype

Principal investigator: Joel Garbow, PhD, a professor of radiology at Washington University School of Medicine and a research member of Siteman Cancer Center

Goal: To develop a greater understanding of the factors that affect the growth of recurrent glioblastoma and, ultimately, develop novel therapies to treat this incurable tumor

Description: Glioblastoma remains the most common malignant brain tumor. Despite state-of-the-art treatment, including surgery, chemotherapy and radiation, these tumors are incurable. Inevitably, the vast majority will recur, becoming more aggressive and invasive in the process. The goal of this work is to develop a greater understanding of the factors that affect the growth of recurrent tumors, and novel therapies. Using a novel animal model of recurrent tumor, researchers will test optimal treatment strategies. They will explore advanced imaging techniques to noninvasively identify tumors and assess early treatment responses, using methods that can be easily translated into the clinic. The scientists also will study how the molecular properties of tumors change in response to radiation therapy, and how these changes affect the way that the body’s own immune system, either alone or supplemented with additional therapies, is able to fight off the growth recurrent tumors.


Title: Characterization and Tumorigenic Action of Osteolineage Cells in the Breast Cancer Microenvironment

Principal investigator: Roberta Faccio, PhD, a professor of orthopedic surgery at Washington University School of Medicine and a research member of Siteman Cancer Center

Goal: To define the phenotype of “bone-like” stromal cells and how they affect tumor growth and metastasis, which ultimately might assist doctors in determining cancer severity and devising new anti-cancer treatments

Description: Working in mouse models of tumors, researchers have discovered that some cells in breast, lung or skin tumors have features that are normally seen only in bone cells. These “bone-like” cells also are present in about 3 percent of lung, breast and skin tissues of normal mice. However, their numbers increase severalfold when tumor cells are injected in the mouse, and, remarkably, they pass into the blood stream when tumors are present. The scientists also find that ectopic “bone-like” cells enhance tumor growth. They hypothesize that these “bone-like” cells are part of the body’s response to a tumor to facilitate tumor initiation, growth and metastasis. The proposed research will define the phenotype of these cells and how they affect tumor growth and metastasis. Results may impact future patient care, as the presence of these cells might tell doctors about the severity of cancer and may help researchers devise new anti-cancer treatments.


Title: Role of Interferon Regulatory Factor 4 in Human T Cell Leukemia Virus-Associated Adult T Cell Leukemia Lymphoma 

Principal investigator: Lee Ratner, MD, PhD, a professor of medicine at Washington University School of Medicine and a research member of Siteman Cancer Center

Goal: To understand the role of the IRF4 protein in adult T-cell leukemia lymphoma, which will also will help decipher its role in other cancers, including multiple myeloma and lymphoma, and help develop novel treatment approaches

Description: Human T-cell leukemia virus type 1 is the cause of a refractory T cell cancer, adult T-cell leukemia lymphoma (ATL). This project is based on exciting new data that mutations are common in genes that code for a pathway that allows the T cell receptor to induce cell growth. Notably, researchers found that one of these components, interferon regulatory factor 4 (IRF4), is overexpressed in almost all cases, as a result of IRF4 gene mutation and/or amplification, or mutation of genes in the pathway upstream of IRF4. The scientists will determine in tissue culture and mouse models the effect of IRF4 overexpression on T cell growth and proliferation. In future studies, they’ll examine in mice the effects of IRF4 inhibitors on ATL growth. Overall, these studies have the potential to lead to an important clinical advance in ATL treatment, which could have applications in other leukemias or lymphomas.


Title: Development of a Superior Mobilizing Regimen for Hematopoietic Stem Cell Transplantation

Principal investigator: Michael Rettig, PhD, an associate professor of medicine at Washington University School of Medicine and a research member of Siteman Cancer Center

Goal: To develop a new method to harvest healthy blood stem cells from the bone marrow of donors to use as transplants for patients with leukemia. In addition to mobilizing healthy stem cells from donors, this new method also might be useful in getting leukemia cells out of the bone marrow and into the blood, where they will be more sensitive to killing by chemotherapy drugs 

Description: The only curative therapy for many patients with blood cancers and bone marrow failure is to administer transplants of healthy blood stem cells derived from the bone marrow of a donor. This process is called hematopoietic stem cell transplantation (HSCT). One key obstacle to the broader success of HSCT is collecting a sufficient number of blood stem cells to create an effective transplant. Researchers are developing a new method to rapidly and efficiently harvest healthy stem cells from the blood of donors using two drugs that have never been combined before. One detaches the stem cells from the bone marrow, while the second not only detaches the stem cells from the bone marrow but also helps them exit the bone marrow and enter the blood stream, where physicians can collect them. This procedure is expected to shorten the time required for donors to donate stem cells, significantly reduce costs and increase the utility of stem cell transplantation. The procedure also might root out leukemia cells from the bone marrow environment, where they are protected from chemotherapy, and move them into the blood, where they should be sensitive to the effects of cytotoxic chemotherapy, a process called chemosensitization.


Title: Memory-Plasticity Crosstalk in Cancer Cells

Principal investigator: Amit Pathak, PhD, an assistant professor of mechanical engineering and material​s science at Washington University School of Engineering & Applied Science and a research member of Siteman Cancer Center 

Goal: This project will investigate whether invasive breast cancer cells remember their primary tumor environment even after they escape to healthy tissue 

Description: Metastasis is driven by the ability of cancer cells to thrive in distinct tissues and organs. This seamless adaptability of cancer cells to new environments is recognized as “plasticity.” However, it remains unknown whether the invasive cancer cells store any memory of past environments. The central hypothesis of this proposal is that breast cancer cells store a mechanical memory of their past environment through discrete memory-storing signals. Inhibition of this memory-storing signaling could negate the mechanical priming of cancer cells by their primary breast tumor. Researchers will develop innovative devices that integrate multiple steps of the breast tumor invasion trajectory. This is a necessary first step toward strategies to modulate the storage of the tumor memory in escaped breast cancer cells. The knowledge of memory-storing signaling targets in breast cancer cells may open new avenues for therapeutics by altering their ability to invade through healthy tissue.


Title: Posttranscriptional control of breast tumor growth and metastasis

Principal investigator: Jianguo Liu, MD, PhD, an associate professor of immunobiology and internal medicine at Saint Louis University School of Medicine and a research member of Siteman Cancer Center 

Goal: To learn what causes the unstoppable growth of cancer cells, with a focus on the role of a newly discovered protein named MCPIP1

Description: The researchers recently found that a new protein named MCPIP1 (Monocyte Chemotactic Protein Induced Protein-1) plays an important role in the control of breast tumor growth. They found that low MCPIP1 levels in tumors were strongly associated with poor survival of breast cancer patients over the 13 years following surgery. When the scientists expressed MCPIP1 in tumor cells, tumor cells were dead and tumors disappeared in animal study. The researchers think MCPIP1 is a powerful new target for breast cancer treatments. They plan to study how MCPIP1 suppresses breast tumor growth, why MCPIP1 levels are lower in tumor cells and what drugs can induce MCPIP1 in breast tumor cells. The results of this study will provide a basis to use MCPIP1 as a new breast cancer treatment.