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Pancreatic Cancer Action Network-AACR Career Development Awards

The Pancreatic Cancer Action Network-AACR Career Development Awards represent a joint effort to encourage and support junior faculty, who have completed their most recent doctoral degree or medical residency within the past 11 years, to conduct pancreatic cancer research and establish successful career paths in this field. The research proposed for funding may be basic, translational, clinical, or epidemiological in nature and must have direct applicability and relevance to pancreatic cancer.

2017 Grantees

Doles_90x110.jpgJason Doles, PhD
Senior Associate Consultant
Mayo Clinic
Rochester, Minnesota
Metabolic alterations driving PDAC-associated muscle wasting

Scientific Statement of Research
Cachexia is a devastating muscle and fat wasting syndrome that affects many individuals with chronic disease, especially cancer. Pancreatic cancer patients are particularly at risk, with up to 70-80 percent exhibiting significant muscle wasting. This is a troubling statistic given the tight correlation between muscle wasting and patient outcomes, including mortality, morbidity, response to chemotherapy, and surgical prognosis. Despite decades of extensive pre-clinical/clinical research, therapeutic options for cachexia are limited. Dr. Doles’ team aims to understand how muscle repair and regeneration are impaired in pancreatic cancer-associated cachexia. This proposal focuses on metabolic regulation of skeletal muscle stem cells (satellite cells), and will dissect how pancreatic cancer-associated secreted factors disrupt satellite cell metabolism and muscle regeneration. Successful completion of these studies will pave the way for future work investigating metabolic interventions capable of stimulating satellite cell expansion, thus boosting the endogenous regenerative capacity of skeletal muscle in pancreatic cancer patients.

Biography
Dr. Doles earned an AB in political science and biology (2003) from Brown University. He received his PhD (2010) from MIT where he studied mechanisms of chemotherapeutic resistance with Dr. Michael Hemann. As a postdoctoral fellow, Dr. Doles transitioned to adult stem cell research in murine skin with Dr. Bill Keyes (CRG Barcelona), and in murine skeletal muscle with Dr. Bradley Olwin (CU-Boulder). He joined the Mayo Clinic Rochester as an assistant professor of biochemistry and molecular biology in 2016 where his lab studies adult stem cell dysfunction in skeletal muscle wasting disorders.

Acknowledgement of Support
My primary expertise is adult skeletal muscle stem cell regulation. As a relatively new independent investigator, this 2017 PCAN-AACR Career Development Award will facilitate my transition to independence and  help focus my muscle wasting program on pancreatic cancer, where improvements in muscle mass/function would greatly improve patient outcomes.

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Haoqiang Ying, MD, PhD
Assistant Professor
University of Texas MD Anderson Cancer Center
Houston, Texas
The regulation of oncogene addiction by YAP pathway in pancreatic cancer

Scientific Statement of Research
Despite the essential role of oncogenic KRAS in driving pancreatic tumorigenesis, a subgroup of tumors evolves to rely less on KRAS oncogene for survival, which contributes to the highly heterogeneous nature and poor prognosis of pancreatic cancer. However, the molecular determinants for KRAS-independency that may serve as context-specific vulnerabilities are still ill-defined. By using an inducible mouse pancreatic cancer model, Dr. Haoqiang Ying has recently demonstrated that a subset of advanced tumors will eventually grow independent of KRAS oncogene, and these tumors are highly reminiscent of those human pancreatic tumors that are relatively resistant to KRAS inhibition and exhibit the worst prognosis. For the proposed project, Dr. Ying and his research team aim to elucidate the molecular mechanisms that lead to the bypass of KRAS-dependency in advanced tumors. The long-term goal is to develop effective targeted approaches and achieve sustainable therapeutic responses for pancreatic cancer.

Biography
Dr. Ying obtained his MD degree from Peking Union Medical College, China in 2000 and received the PhD degree in biochemistry from Boston University School of Medicine in 2006. He then worked as postdoctoral fellow at Dana-Farber Cancer Institute where he used genetically engineered mouse models to study the dependence on KRAS oncogene in advanced pancreatic cancers and the role of KRAS-driven metabolism reprogramming in tumor maintenance. Dr. Ying joined MD Anderson Cancer Center in 2014 as an assistant professor. His research program is focused on understanding context-specific regulation of KRAS-dependency and its related metabolism programs in pancreatic cancer.

Acknowledgement of Support
The Career Development Award will not only provide funding support essential for the proposed research project, it will also foster critical scientific collaborations through interactions with peers and experts in the PanCAN community.

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Ingunn M. Stromnes, PhD
Assistant Professor
University of Minnesota
Minneapolis, Minnesota
Enhancing the efficacy of engieneered T cell therapy for pancreatic cancer

Scientific Statement of Research
Pancreatic cancer is highly resistant to therapies, including immunotherapy. Dr. Stromnes has developed a new cellular immunotherapy that genetically reprograms T cells to express a tumor-reactive receptor, thereby, enabling T cells to recognize and kill pancreatic tumor cells. Over time, however, the engineered T cells become dysfunctional only within the suppressive pancreatic tumor microenvironment thereby limiting efficacy. Dr. Stromnes’s project entails studying the role the tumor microenvironment plays in inducing engineered T cell dysfunction to devise new immunotherapeutic strategies to target this disease.

Dr. Stromnes will test the hypothesis that a greater understanding of the molecular and metabolic features of engineered T cell subsets infiltrating PDA will inform new ways to manipulate T cells for greater therapeutic benefit. Dr. Stromnes and her research team will test the hypothesis that modulating non-redundant signaling pathways in T cells can safely increase anti-tumor efficacy in preclinical animal models. Promising strategies will then be evaluated in combination with modulating suppressive cells in the tumor microenvironment and further developed for clinical testing. The proposed studies are designed to identify translatable strategies to enhance the efficacy of cellular immunotherapies for pancreatic cancer patient treatment.

Biography
Dr. Ingunn Stromnes obtained predoctoral training at the National Institutes of Health, followed by a PhD in immunology from the University of Washington. As a postdoctoral scientist at the Fred Hutchinson Cancer Research Center, she developed a novel and promising immunotherapy by genetically engineering T cells to infiltrate and attack pancreatic cancer without the toxic side effects of chemotherapy. Dr. Stromnes is now a faculty member at the University of Minnesota where she and her lab will continue to push the boundaries of cellular engineering to create safe and effective immunotherapies for pancreatic cancer patients.

Acknowledgement of Support
It is a distinct honor to be selected for the 2017 Pancreatic Cancer Action Network-AACR Career Development Award. I believe there is reason to be optimistic that immunotherapies can successfully be designed to safely and effectively eradicate pancreatic cancer in patients, and this award exemplifies a similar confidence from the pancreatic cancer research community. I am truly grateful to the Pancreatic Cancer Action-Network and the AACR for their support and am honored to represent them during our pursuit of designing effective immunotherapies for pancreatic cancer patients.

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