Directors: William Gillanders, MD, and Channing Der, PhD
The Career Enhancement Program is a joint venture between the SPORE in Pancreatic Cancer, Washington University School of Medicine (WUSM), and Siteman Cancer Center (SCC). The primary objective of the Career Enhancement Program is to enhance pancreatic cancer research by providing financial support and mentoring for investigators who are new to the field to help build translational research careers in pancreatic cancer. The research initiatives that will be funded by the Career Enhancement Program are expected to have a major translational component, focusing on etiology, prevention, diagnosis, early detection, treatment or population science in pancreatic cancer.
The Career Enhance Program's goals are as follows:
- Recruit and support new investigators to the field of pancreatic cancer research. The Career Enhancement Program is able to support a maximum of two investigators per year. Each investigator will be supported for up to two years, and the money can be used for salary support, laboratory supplies or tuition. The Career Enhancement Program will support both new investigators and established faculty members who are new to the field of pancreatic cancer research.
- Provide mentoring to junior faculty members. Truly successful Career Enhancement Program awardees will be those who subsequently apply for and receive independent external funding to support their pancreatic cancer research careers. The Career Enhancement Program will foster this success by mentoring junior faculty members one-on-one, providing numerous opportunities for research training and didactic instruction, and assisting in the development and review of grant applications.
- Promote participation of women and under-represented minorities in pancreatic cancer research. The Career Enhancement Program will specifically seek to increase the diversity of those participating in pancreatic cancer research through numerous outreach, recruitment, training and retention activities.
The Career Enhancement Program will select awardees from the collaborating SPORE institutions and from other appropriately qualified institutions. Financial support (salary, research supplies and tuition) will be provided for awardees for up to two years. The Career Enhancement Program will facilitate interactions between awardees and all members of the SPORE, emphasizing the basic and clinical science cross-fertilization that is essential to translational research. The SCC, WUSM, and our collaborating SPORE institutions provide outstanding opportunities for career development in translational pancreatic cancer research. We have the broad research base, existing and continually evolving new collaborations, basic science and clinical programs in pancreatic cancer that make the Career Enhancement Program a success.
We have established intra-SPORE collaborations with the University of North Carolina, University of Rochester and Johns Hopkins University, broadening the Career Enhancement Program applicant pool and helping to match the interests of junior investigators with local expertise and need. The Career Enhancement Program will be open to all institutions participating in the SPORE.
Learn How to Apply and Download the Application Forms for the Career Enhancement Program.
Aadel Ahmed Chaudhuri, MD, PhD
Washington University School of Medicine
Project Title: Circulating Tumor DNA for Early Treatment Response Assessment of Pancreatic Cancer
Lay Abstract: Pancreatic cancer is among the deadliest cancers worldwide, and surgical resection and stereotactic body radiotherapy (SBRT) play major roles the treatment of localized disease. Unfortunately, there is no modality in clinical practice that can reliably detect molecular residual disease (MRD) after surgery, or distinguish between post-treatment inflammation/fibrosis and residual disease after SBRT. Here we will attempt to address these issues by measuring circulating tumor DNA (ctDNA) in the blood plasma using the CAPP-Seq method to assess response to therapy at a molecular level. Our goal is to show that this method can reliably detect MRD shortly after treatment completion. If successful, this would pave the way for personalized response-adapted therapy via dose escalation for patients with detectable MRD and avoid excess therapy for those with undetectable MRD. Our aim is that this research will improve pancreatic cancer survival through the application of precision medicine.
Yuliya Pylayeva-Gupta, PhD
University of North Carolina at Chapel Hill
Project Title: Role of Immunosuppressive B Cells in Pancreatic Cancer
Lay abstract: Pancreatic cancer is a very aggressive disease. It is the 4th leading cause of cancer deaths in the USA. Only 6% of patients who can undergo surgery will survive past five years. Late diagnosis and lack of good treatment options are some of the reasons for this outcome. Recent progress in cancer immune therapy showed effect in cancers such as relapsed leukemia and metastatic melanoma. Unfortunately, immune therapy was not effective in patients with pancreatic cancer. One explanation for this result is that pancreatic cancer blocks immune responses against cancer. Thus, understanding how cancer promotes immune suppression is vital to our ability to treat this deadly disease. Our initial work has revealed that B cells promote growth of pancreatic cancer. However, it is not clear how B cells promote cancer growth, and how targeting these cells can benefit patients. We propose to understand how B cells function in pancreatic cancer. The goal of this research project is to find new targets that can block immune suppression in pancreatic cancer. Using both mouse models of pancreatic cancer and patient samples, we hope to identify B cell based targets in pancreatic cancer. We ultimately hope to translate our findings into effective therapies that may also work with existing immune therapy treatments.
Kian-Huat Lim, MD, PhD
Project Title: Evaluation of IRAK4 as a Novel Immunotherapeutic Target in Pancreatic Cancer
Lay Abstract: To date, the prognosis for pancreatic cancer remains dismal. To improve patient outcome, novel and effective therapeutic strategies must be developed. Immunotherapy using checkpoint inhibitors has revolutionized the outlook of other cancer types including melanoma, lung and renal cancer, and yet is largely unsuccessful in pancreatic cancer. Our lab recently found that pancreatic cancer cells “armored” themselves by activating their own innate immune system, a self-defense mechanism that is usually summoned when cells are injured or invaded by microorganisms. We now believe, based on recent findings in our lab, that pancreatic cancer cells can utilize the same mechanism to invoke a fibrotic and inflamed tumor environment that renders immunotherapy ineffective. Our approach is to “deactivate” such defense mechanism by inhibiting Interleukin-1 Receptor-Associated Kinase 4 (IRAK4), the master switch that controls the innate immune pathway. By doing so we found that pancreatic cancer cells become greatly weakened and are now responsive to immunotherapy. In this proposal, we will further investigate the role of IRAK4 in other cell types such as immune cells and fibroblasts within the pancreatic tumor, which will yield valuable knowledge to optimize future clinical trial design. In addition, we will test two new, highly potent IRAK4 inhibitors in combination with immunotherapy in mouse models with the goal of advancing a promising regimen that can be tested for pancreatic cancer patients.