Siteman Cancer Center Announces 2024 American Cancer Society-Funded Pilot Projects 

Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine is excited to announce the next cohort of pilot projects funded by the Institutional Research Grant from the American Cancer Society. The $480,000 grant supports 12 pilot projects from 2022-2024, including the four new projects described below.  

Under the leadership of Jason Weber, PhD, who has been the principal investigator of the grant since 2011, these awards support independent, self-directed investigators early in their careers and enable them to conduct research in areas of special interest to the American Cancer Society. 

 Washington University has funded early-career oncology researchers with this grant since 1958. Learn more about the projects announced in 2023 here. 

 

 

 

 

Project Title: Investigating the Role of KDM6A in Human Squamous Cell Carcinoma 

Principal Investigator: David Chen, MD, PhD 

 Summary: Skin cancer is diagnosed in more people in the U.S. each year than all other cancers combined. Cutaneous squamous cell cancer (cSCC) is a non-melanoma skin cancer that, together with basal cell cancer, accounts for most skin cancer diagnoses. Statistics on the number of people diagnosed with cSCC and their outcomes are not captured in national cancer registries. Correspondingly, knowledge of how cSCC forms and how best to prevent its development (and even the research tools needed to study these questions) are underdeveloped. We recently discovered that the protein KDM6A likely plays an important role in restraining cSCC development because mice without KDM6A and the well-established tumor suppressor Trp53 will inevitably develop cSCC. Importantly, in human tumors, it appears that KDM6A dysfunction may happen early in cSCC development, but the details of how this makes skin susceptible to cancer are unknown. This project will use state-of-the-art genomics techniques to discover how KDM6A dysfunction occurs in human cSCC and what the consequences of this dysfunction are in the context of skin cancer development. Knowledge gained from this project could lead to a deeper understanding of the early events in skin cancer development and to newer and better ways to prevent and treat cSCC. 

 

Project Title: Immunogenicity of a Personalized Neoantigen DNA-based Vaccine in Patients with Glioblastoma 

Principal Investigator: Tanner Johanns, MD, PhD 

Summary: Researchers have performed a clinical trial in patients with brain tumors where they received a novel vaccine encoding targets derived specifically from their individual tumors. This personalized vaccine strategy takes advantage of genetic changes that occur in tumor cells, called neoantigens, which can serve as highly tumor-specific targets for the immune system. While this approach is not new, the vaccine platform used in this study is novel due to the increased number of neoantigens targeted per patient and the inclusion of an immune-boosting agent to improve vaccine efficacy. This application aims to analyze blood samples from patients in this study to assess the immune response to this novel vaccine platform. The results will provide key insights into factors that drive effective neoantigen-specific immune responses – insights that have been limited in prior neoantigen vaccine studies due to the restricted number of neoantigens included and the weak efficacy of the vaccine platforms used. The data generated by this application will guide the design of next-generation neoantigen vaccines to be tested in subsequent clinical trials. The goal is to optimize this immune therapy approach so it can be incorporated into the standard treatment regimen for patients with brain tumors. However, these findings have applicability to nearly all other tumor types as well, so the implications of the proposed work extends beyond patients with brain tumors. 

Project Title: Evaluation of Cell-free DNA Fragmentation for Non-invasive Molecular Profiling and Outcome Prediction of Meningiomas  

Principal Investigator: Dimitrios Mathios, MD 

Summary: Meningiomas are the most common brain tumors, and their clinical course can vary significantly with a subgroup of them exhibiting a very aggressive behavior leading to rapid neurological worsening, need for multiple surgical and oncological treatments and eventually death. This proposal capitalizes on the significant progress recently made in the molecular understanding of this disease and introduces several innovations in liquid biopsy technology development, to build a noninvasive blood test that detects these tumors before symptoms arise, as well as assesses their biological aggressiveness and provides insight into the molecular mechanisms of each patient’s tumor to better guide and tailor treatment strategies. 

 

 

Project Title: Cancer Epidemiology and Genomic Analysis of Kaposi Sarcoma-associated Herpesvirus in Kenya 

Principal Investigator: Thomas Odeny, MBChB, MPH, PhD 

Summary: The global cancer burden is surging, with 70% of new cases arising in low- and middle-income countries, including Kenya. Yet Kenya lacks investigator-initiated cancer clinical trials. The National Cancer Institute (NCI) Center for Global Health is encouraging NCI-designated cancer centers to advance global oncology by identifying opportunities for cancer research and control globally. This two-part project aims to: 

Develop a comprehensive electronic database of all cancer patients at the Jaramogi Oginga Odinga Teaching and Referral Hospital in Kisumu, Kenya. Collecting patient demographics and clinical data will enhance the ability to assess the patient populations and identify potential clinical trial candidates. This approach will yield a more accurate understanding of the burden of cancer within the hospital’s 10-million-person catchment area.

Conduct a proof-of-concept genomic study to demonstrate the database’s capability for comprehensive data extraction and high-quality genomic studies, in collaboration with the Ratner Lab. The project will focus on cancers caused by the Kaposi sarcoma-associated herpesvirus (KSHV), which is highly prevalent among people living with HIV. Researchers will conduct DNA and single-cell RNA analysis of KSHV, which causes Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease. Patients infected by KSHV van have a broad range of diseases, ranging from asymptomatic to Kaposi sarcoma tumors on the skin, to Kaposi sarcoma tumors in the lungs and gastrointestinal tract, to aggressive types of lymphoma that can be rapidly fatal. By genotyping, we will identify KSHV subtypes more likely to cause severe diseases. This project aligns with the NCI Center for Global Health’s mandate of advancing global oncology within NCI-designated cancer centers and will set the stage for Siteman Cancer Center’s broader participation in global cancer clinical trials.