Career Enhancement Program (CEP)

Directors: William Gillanders, MD, and Channing Der, PhD

Program Application Information

The Pancreas SPORE will fund one to two investigators per year for the life of the SPORE. The 2020 deadline for applications is April 30, 2020. The award will be up to $75,000 per year for up to two years, beginning on July 1, 2020. Download the forms below to submit your project: Request for Applications and Instructions; Face Page.

SPORE CEP Overview

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.

CEP Past Awardee’s

The CEP has funded a total of four projects.  These projects have led to two clinical trials in pancreatic cancer.  CEP-funded investigators have published in top-tier journals, including Cancer Discover, Clinical Cancer Research, and Cancer Immunology Research. Thus, our CEP investments, in combination with our DRP awards, account for three out of four of the projects in this SPORE renewal application and a significant number of new trials for pancreatic ductal adenocarcinoma (PDAC) patients. These metrics highlight the quality of our applicants and the projects we foster with the developmental mechanisms. We aim to continue our success in this area. A summary of our CEP awardees and their collaborative, high-impact productivity is provided below.

2016 Awardee

Kian-Huat Lim, MD, PhD

Evaluation of IRAK4 as a Novel Immunotherapeutic in Pancreatic Ductal Adenocarcinoma. Immunotherapy using checkpoint inhibitors has revolutionized the outlook of several cancers, including melanoma, lung, and renal cancer, and yet has been largely unsuccessful in pancreatic cancer. Lim found that pancreatic cancer cells “armor” themselves by activating their own innate immune system, a self-defense mechanism that is usually summoned when cells are injured or invaded by microorganisms. Recent findings in his lab revealed that pancreatic cancer cells can utilize the same mechanism to invoke a fibrotic and inflamed tumor environment that renders immunotherapy ineffective. Lim found that deactivating this defense mechanism by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4), the master switch that controls the innate immune pathway, caused pancreatic cancer cells to become greatly weakened and thus responsive to immunotherapy. His lab investigated the role of IRAK4 in other cell types within the pancreatic tumor, such as immune cells and fibroblasts, which will facilitate optimization of future clinical trial design. The results of Lim’s research were leveraged to obtain additional grants, including an American Cancer Society Award and a National Cancer Institute R37. He has published five articles in journals such as Clinical Cancer Research, Oncotarget, Molecular Cancer Therapeutics, Cancer Research, and Gut. CEP funding of Kian’s project led to development of a clinical trials (NCT03496662 & NCT03851237).

2017 Awardee

Yuliya Pylayeva-Gupta, PhD

Role of Immunosuppressive B Cells in Pancreatic Cancer.

Understanding how cancer promotes immune suppression is vital to our ability to treat Pancreas Ductal Adenocarcinoma. The overall goal of Dr. Pylayeva-Gupta’s initial research revealed that B cells promote growth of pancreatic cancer, and the goal of her research was to identify new targets that can block immune suppression in pancreatic cancer.  Her team has been testing strategies that block immune suppressive pathways in the tissue microenvironment and enhance the impact of T cell-reinvigorating therapies. She has published her research in top journals, including Cancer Discovery, Cancer Immunology Research, and Cytokine. The results of her work have led to multiple new grants in pancreatic cancer from the V Foundation for Cancer Research, Concern Foundation Conquer Cancer Now, Department of Defense, and the National Cancer Institute.

2018 Awardee

Aadel Ahmed Chaudhuri, MD, PhD

Circulating Tumor DNA for Early Treatment Response Assessment of Pancreatic Cancer. Pancreatic cancer is among the deadliest cancers worldwide, and surgical resection and stereotactic body radiotherapy (SBRT) play major roles in 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. In his research, Chaudhuri plans to address these issues by measuring circulating tumor DNA (ctDNA) in blood plasma using the CAPP-seq method to assess response to therapy at a molecular level. Chaudhuri’s research aims to provide key data to facilitate development of personalized response-adaptive therapy via dose escalation for patients with detectable MRD and avoid excess therapy for those with undetectable MRD. His research has led to publications in Gastroenterology and Molecular Diagnosis and Therapy. Based on Dr. Chaudhuri’s promising preliminary data this project has now evolved into a prospective longitudinal collaboration with Dr. Ryan Fields.

2019 Awardee

Carl DeSelm, MD PhD

Care Modified Innate Immune Cells for Pancreatic Ductal Adenocarcinoma. Pancreatic cancer remains one of the deadliest cancers and is characterized by a rich infiltration of innate immune cells that are programmed by the tumor to facilitate its own survival, growth, and spread. In other contexts, these same innate immune cells can be potent killers of bacteria, viruses, or even tumor cells. Why they become strong tumor-supportive cells rather than tumor-killing cells and how to reverse this role remain key gaps in knowledge. Using genetic techniques, DeSelm is modifying these innate immune cells with chimeric receptors that, upon tumor binding, initiate a program of anti-tumor activity. These anti-tumor responses range from direct tumor phagocytosis or killing to modulation of the tumor microenvironment to lead to its eventual death. This genetic programming impedes the tumor’s manipulation of innate immune cells. This strategy may become an effective treatment option for pancreatic cancer at all stages. Dr. DeSelm is currently developing a new clinical trial with Dr. David DeNardo of Project 2 that is planned to open in the early 2020’s.

2020 Awardee

Patrick Grierson, MD, PhD

Evaluation of MK2 as a novel Immunomodulatory Target in Pancreatic Cancer.  Pancreatic cancer remains among the deadliest cancers, and is presently unresponsive to targeted or immunotherapies, leaving combination chemotherapies as the primary treatment for advanced disease. However, treatment responses to chemotherapy are neither universal nor durable, largely due to intrinsic signaling events that drive resistance as well as a protective extrinsic tumor microenvironment that limits the delivery of chemotherapy and neutralizes anti-tumor immunity.  In preclinical models, near-complete stromal depletion reverts pancreatic cancer cells into a primitive and more aggressive tumor type and clinically, stromal depletion via addition of hyaluronidase fails to potentiate chemotherapy and may increase toxicity. These findings underscore the need to identify novel therapeutic targets in pancreatic cancer.  Grierson has found that adaptive activation of the MK2/Hsp27 pathway is a novel and major resistance mechanism to genotoxic stress in pancreatic cancer, and that treatment with a novel oral MK2 inhibitor concurrent with chemotherapy greatly augments the efficacy of chemotherapy in preclinical models. Furthermore, targeting MK2 causes marked reduction in stromal density and shifts tumor-infiltrating T cells and myeloid cells to an activated anti-tumor phenotype.  Beyond the CEP award, his work has also led to grant support from the Emerson Collective Cancer Research Fund to further study pancreatic cancer.  Dr. Grierson is currently developing a new clinical trial based on this work.

2020 Awardee

Calvin L. Cole, PhD

Role of CCR2 and CXCR1/2 inhibition on the attenuation of PDAC-related cachexia. Pancreatic cancer is a leader in cancer-related deaths due to the aggressive nature of the disease, treatment intolerance, and/or discontinuation related to cancer-related skeletal muscle wasting (SMW) and decreased quality of life. The Cole laboratory is focused on elucidating the mechanisms of SMW uniquely associated with pancreatic cancer and developing interventions.  Importantly, a large percentage of patients with pancreatic cancer experience cancer-related SMW, and have reduced physical function and response to treatment, increased postoperative morbidity, and shorter life expectancy.  Thus, treatments that attenuate muscle wasting may also improve treatment tolerance, quality of life, and survival.  Recently, Dr. Cole obtained NIH P30 pilot grant funding to evaluate sarcopenia in the KCKO murine model of PDAC developed in Dr. David Linehan’s laboratory via standard histology and novel longitudinal dual-energy X-ray absorptiometry (DEXA) outcomes.  The results of this research revealed several remarkable innovations that were published in PLOS ONE. Most notable was our discovery that PDAC bearing mice faithfully recapitulate the pathophysiology of cancer-related SMW, upregulated systemic and local inflammation (TNF-α, IL-1, and IL-6), and increased tissue-associated cellularity, which are known to be upregulated in animal models of cancer cachexia.  Upregulation of these cytokines have been linked to high levels of the chemokine receptor genes CCR2 and CXCR1/2, which attract myeloid cells to the tumor microenvironment (TME).  The goal of Dr. Cole’s current research is to understand the relationship between secretions from the TME and SMW in a murine model of PDAC and translate these findings into clinically relevant treatments.