Past Pancreatic Cancer Action Network Research Grant Recipients

2007

Samuel Stroum PanCAN-AACR Young Investigator Award for Pancreatic Cancer Research

Hiroyuki Kashiwagi, MD
Targeted delivery of pro-apoptotic therapeutics in pancreatic cancer Washington University, St. Louis, MO

I chose the field of pancreatic cancer research because I was frustrated with the treatment options available for my patients with pancreatic cancer.

To summarize the work of our research project, we have developed peptide antagonists for two distinct anti-apoptotic pathways that are often hyperactive in cancer cells. We have coupled these therapeutic domains with ligands, which preferentially bind to and are internalized by pancreatic cancer cells. In this grant we wish to explore the efficacy and toxicity of these novel dual domain peptides as single therapies and as potentiators of each other and of standard therapies. These studies will be performed in vitro as well as in vivo in mouse models of pancreas cancer.

We anticipate that these studies will establish our novel dual domain therapeutics as effective treatment regimens for pancreatic adenocarcinoma without severe toxicity. Successful completion of the research plan will provide the preliminary data to seek the additional funding which will allow us to initiate an Investigational New Drug application and to initiate a phase I clinical trial of our new drugs. I am thankful to be the recipient of the Samuel Stroum Young Investigator Award, which will allow me to dedicate myself to pancreas cancer research and continue my training towards a career as a clinician-scientist.

Carole and Bob Daly PanCAN-AACR Career Development Award for Pancreatic Cancer Research

Martin E. Fernandez-Zapico, MD
Characterization of the Hedgehog interacting pathways in pancreatic cancer Mayo Clinic, Rochester, MN

Pancreatic cancer research has always attracted me, even as a medical student in Argentina, where I had an opportunity to study the effect of chemopreventive agents in animal models of pancreatic cancer. Before graduation, I was an undergraduate research fellow at the Gastroenterology Research Unit (Mayo Clinic) under the mentorship of Raul Urrutia. During this clerkship, I had the opportunity to study the mechanisms underlying the cancerassociated growth functions of pancreatic cancer cells. Later, I joined Dr. Urrutia’s group as a postdoctoral fellow in order to extend my training in cell/molecular biology, biochemistry and animal models of pancreatic cancer. Together, these experiences have provided the necessary tools and expertise that will allow me to develop as an independent investigator in pancreatic cancer as well as create awareness for the needs in early diagnosis and novel therapeutic tools for this disease.

My long term goal is to improve the quality of life and develop treatments for pancreatic cancer patients derived from fundamental basic science knowledge. My research focus is to better understand the signaling networks involved in pancreatic carcinogenesis in order to find new targets that can contribute to therapy and prevention of pancreatic cancer. I am certain that obtaining the PanCAN Career Development Award will provide the essential support for my development as an independent investigator. This proposal will have a focus on the molecular characterization of the survival cascade mediated by Hedgehog and its signaling interacting pathways in pancreatic cancer.

Nancy Daly Riordan PanCAN-AACR Career Development Award for Pancreatic Cancer Research

Paul J. Grippo, PhD
Evaluating Kras oncogene addiction in pancreatic precancer and cancer Northwestern University, Chicago, IL

In 1995, I was introduced to pancreatic cancer by my academic advisor and mentor, Dr. Eric Sandgren, while doing graduate studies at the University of Wisconsin. At the time, Dr. Sandgren was one of only a handful of researchers to have a NIH/NCI grant focused on pancreatic cancer research, and nearly all of my laboratory work was directed on developing models of pancreatic cancer and using existing ones to understand disease development. I became passionate about my research as I learned about this disease, its late detection, and poor prognosis. PanCAN has also made its mark in my career from its earliest beginnings, and especially since 2002, where my volunteering in a TeamHope Affiliate (Northern Illinois) has brought me eye to eye with patients and their dedicated, driven families and friends. These people (Valerie, Angie, Kim, Linda, Terry, Ed, and Marvin) have touched me the most and encouraged me to keep pushing forward with my research, if not for the present, at least for the next generation. To them and to God, I am truly grateful.

The funds that accompany this award will be used to support a project that will determine if a common genetic mutation in pancreatic cancer (in a gene called Kras) is required for the development and maintenance of both early precancerous lesions (PanINs) and cancer. Findings from this project will help identify the cell types that can give rise to pancreatic cancer and if therapies that target mutations in Kras will be effective at the level of precancer and cancer. By trusting me with this award, PanCAN provides the confidence for me to move forward, the funds with which to begin those endeavors, and the history of success to serve as a template.

Laurie and Paul MacCaskill PanCAN-AACR Career Development Award for Pancreatic Cancer Research

Kimberly Kelly, PhD
Molecular imaging agents for early detection of pancreatic cancer Massachusetts General Hospital, Charlestown, MA

Through participation in a large consortium made up of such distinguished pancreatic cancer researchers as Ronald DePinho, Doug Hanahan, and Tyler Jacks, I became aware of the devastation of the disease and also the lack of available clinical diagnostic tools. This knowledge galvanized me to investigate possibilities that could lead to effective diagnostic tools and potentially improve survival rates.

My research will identify novel molecular markers and develop imaging probes for pancreatic ductal adenocarcinoma (PDAC). Clinical imaging and early detection of pancreatic cancer with the developed imaging agents may substantially decrease the morbidity and mortality of patients diagnosed with pancreatic cancer. Given the lack of diagnostic tools for PDAC, the PanCAN Award is important since it will allow me to focus on these important studies and further this much needed research.

Ralph H. Hruban, M.D. PanCAN-AACR Career Development Award for Pancreatic Cancer Research

Ben Stanger, MD, PhD
Investigation of the pancreatic "ductome" University of Pennsylvania, Philadelphia, PA

I first became aware of the devastating impact of pancreatic cancer over 10 years ago, when a patient I was caring for as a medical student was diagnosed with the disease. I still vividly recall the powerless feeling, which entrapped him, his family, and his medical providers. With each subsequent case, I have been reminded of the desperate need for earlier diagnosis and better treatment.

The efforts of PanCAN and other patientoriented organizations have generated significant momentum in pancreatic cancer research, and have also served to remind those of us working in the field that pancreatic cancer is a very “real” problem. My project, “Investigation of the Pancreatic Ductome,” seeks to compare the putative precursors of pancreatic cancer with their normal embryonic and adult pancreas counterparts. The support being provided by PanCAN will allow me to explore this question as part of a broader interest in the relationship between cancer development and embryonic development. It is a particular distinction to have an award named in honor of Ralph Hruban, MD, whose careful studies have defined pancreatic cancer precursors. This PanCAN award gives me the opportunity to perform the type of study that falls outside of a typical NIH grant and I hope these efforts will provide the information that will allow us to go after the “Achilles’ heel” of this tumor.

Skip Viragh PanCAN-AACR Career Development Award for Pancreatic Cancer Research

Huamin Wang, MD, PhD
Functional study of hematopoietic progenitor kinase-1 in pancreatic cancer MD Anderson Cancer Center, Houston, TX

I am a pathologist specializing in research in the gastrointestinal tract, liver, and pancreas. My daily clinical services are to review the histologic slides from many different types of cancer specimens. I was fascinated by the fact that most of the pancreatic ductal carcinomas are moderately or well differentiated and yet they behave as one of the most lethal diseases among all human malignancies. Clearly, we have to look beyond the histology to understand the biology of pancreatic cancer. This led me to pursue my laboratory research focusing on the underlying molecular mechanisms of pancreatic cancer.

I am deeply honored to have been selected for the PanCAN Career Development Award. This funding will provide essential support during my career transition period to further dissect the molecular mechanisms involved in pancreatic cancer. I am also very grateful to have the opportunity to work and to collaborate with many outstanding clinicians and researchers at the University of Texas M. D. Anderson Cancer Center who dedicate their careers to pancreatic cancer. Through our multidisciplinary teamwork, I believe that we will make a difference in pancreatic cancer care tomorrow.

Seena Magowitz PanCAN-AACR Career Development Award for Pancreatic Cancer Research

Rebekah White, MD
Prostate stem cell antigen: a specific target for pancreatic cancer therapy Duke Medical Center, Durham, North Carolina

My interest in and relationship to pancreatic cancer started in my residency and subsequent surgical oncology fellowship at Memorial Sloan- Kettering Cancer Center. As a surgeon, I learned that one of the most difficult conversations I had to have was meeting patients and their families to share the news that surgery was not an option, and therefore long-term outcomes were not good.

My research plans involve investigating prostate stem cell antigen (PSCA), a GPI-anchored cell surface protein that is specifically over expressed in pancreatic cancer and has been implicated as potential therapeutic target. As a surgical resident at Duke University, I engaged in clinical research on neoadjuvant therapy for pancreatic cancer under the mentorship of Dr. Douglas Tyler and spent three years working with Dr. Bruce Sullenger, whose laboratory is focused on the development of innovative nucleic acid therapeutics. When I returned to Duke as a faculty member this summer, I will resume research under the mentorship of Dr. Sullenger and plan to use an iterative in vitro selection technique (SELEX) to generate nuclease-resistant RNA ligands (aptamers) that bind and inhibit PSCA. Such molecules may validate PSCA as a therapeutic target and may be useful as therapeutic agents themselves. This award not only helps to initiate my research program but also demonstrates PanCAN’s support of physician-scientists and translational research in pancreatic cancer.

Development of immune-modulating therapies delivered directly to the pancreatic tumor site

Pinku Mukherjee, PhD, Mayo Clinic
Current protocols for the treatment of pancreatic cancer are not as effective as we desire. Novel therapies such as cancer vaccines that target specific proteins only on the tumor present an attractive alternative with the expectation that this approach will cause fewer side effects and prevent metastasis and recurrence better than standard therapies. To prevent metastasis and recurrence, cancer vaccines must generate immune memory against these tumor-specific proteins. So far, this has not been possible because tumors have adopted ways to successfully escape recognition and killing by the immune cells. Several known agents that can reverse immune escape have previously been tested but with modest clinical responses because the agents were administered systemically and may have never reached the tumor site. Goal: Our goal is to target these novel immune-modulating agents directly to the pancreatic tumor site using a tumor-specific MUC1-antibody as a carrier. Hypothesis: We hypothesize that a robust anti-tumor response along with a strong memory response will be generated when MUC1/KRAS-based vaccine is combined with novel immune modulating agents that are delivered directly to the pancreatic tumor site. To test the hypothesis, we have generated an appropriate animal model that develops spontaneous pancreatic cancer and appropriately mimics the human disease. These studies could form the basis for targeting other agents directly to the pancreas site. If successful, the results from these studies could help us develop a new combination modality for the treatment of localized and disseminated tumors.

Activated kras G12D and oncogene dependence in pancreatic cancer

Sunil R. Hingorani, MD, PhD
Fred Hutchinson Cancer Research Center

Activating mutations in the RAS family are among the most frequently encountered oncogenic events in human malignancies. In pancreas cancer, KRAS mutations appear to be essential for disease initiation. It remains unknown, however, whether sustained mutant KRAS activity is required to maintain the preinvasive or invasive and metastatic stages of the disease. In other words, does oncogenic KRAS subvert and rewire intracellular signaling networks to create a situation of dependence or ‘addiction’ to its effects? If so, then the very event that endows the pancreatic cancer cell with its lethal abilities may also represent the means to its undoing. We have previously shown that targeted conditional expression of endogenous KrasG12D in progenitor cells of the murine pancreas induces the development of all three stages of preinvasive pancreas cancer lesions, termed pancreatic intraepithelial neoplasias (PanINs). These lesions can progress of their own accord, or can be hastened to progress in the setting of additionally targeted tumor suppressor gene mutations, to fully invasive and widely metastatic pancreatic ductal adenocarcinoma (PDA). We now propose experiments to establish whether physiologic levels of oncogenic Kras create a state of cellular dependence in vivo in faithful animal models of human PDA and rigorously demonstrate whether activated Kras represents a valid therapeutic target.

Using a genomic scale to identify the genes that play a role in the ability of pancreatic cancer to metastasize to other organs

Christine Iacobuzio-Donahue, MD, PhD
Johns Hopkins

We propose to use a novel technology called functional allelotyping to investigate those changes in gene expression that accompany the formation and spread (“metastasis”) of pancreatic cancer. Functional allelotyping is unique compared to other whole genome evaluation methods because it can detect abnormalities of both DNA content and epigenetic control of gene expression in the same sample. Studies that focus on pancreatic cancer metastasis have the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for intervention.

Assessing mechanisms and therapeutic potential of an aspartyle protease in pancreatic cancer

Douglas Hanahan, PhD
University of California, San Francisco

Our study is focused on the underlying mechanisms of pancreatic cancer which we believe can potentially have important implications for pancreatic cancer therapy. We are testing the hypothesis that Cathepsin E expression in neoplastic ductal epithelial cells of the pancreas serves to functionally promote carcinogenesis and is, therefore, an attractive therapeutic agent. We will test this hypothesis by crossing a Cathepsin E gene knockout mouse into the pancreatic tumor model. We have also identified an FDA approved drug, Ritonavir, which inhibits Cathepsin E. Once we have identified a role for this enzyme in ductal carcinogeneisis we will then evaluate the therapeutic potential of targeting this enzyme in improving disease prognosis. These tools will enable us to evaluate the effect of Cathepsin E loss on lifespan of tumor bearing mice and also the effects on the parameters of the tumor and its microenvironment.

Activin signaling in the development of pancreatic cancer precursor lesions

Gloria Su, PhD
Columbia University Medical Center

Genetic engineered mice have been effective tools for cancer modeling and pathway studies. In our application, we propose to study activin signaling pathway in genetic engineered mice, because we have previously shown that activin signaling pathway is important for human pancreatic tumorigenesis and this tumor-suppressive pathway has not been investigated in vivo. Our preliminary data shows that the inactivation of activin pathway in combination with Kras oncogenic activation can lead to the development of mucinous cystic lesions in the pancreases of the mice. We plan to utilize these mice to further our understanding of the tumorigenesis from non-invasive mucinous cystic precursor lesions to invasive cancer in human pancreases. By studying these genetic engineered mice, we hope to understand the predetermination of the three common precursor lesions, PanIN (pancreatic intraepithelial neoplasias), IPMN (intraductal papillary mucinous neoplasms), and MCN (mucinous cystic neoplasm), at the onset of pancreatic tumorigenesis.

2006
2006 PanCAN-AACR Career Development Award
Dr. Ru Chen
University of Washington
Identifying the role of the notch signaling pathway in the development of pancreatic ductal adenocarcinoma

2006 PanCAN-AACR Michael Landon Career Development Award
Dr. Brian C. Lewis
University of Massachusetts Medical School
Development of the early biomarkers of pancreatic cancer to improve early detection while the cancer is still curable

2006 PanCAN-AACR Career Development Award
Daoyan Wei, PhD
MD Anderson Cancer Center
The role of KLF4a in pancreatic cancer

2006 PanCAN-ASCO Career Development Award
David Chang, MD, PhD
MD Anderson Cancer Center
Treating Pancreatic Cancer with the Well-characterized Anti-allergy Drug Cromolyn, Through a Novel Mechanism of Action

2006 PanCAN-ASCO Samuel Stroum Young Investigator Award
Jennifer Tseng, MD
University of Massachusetts Memorial Medical Center
Development of a malignancy prediction rule for cystic lesions of the pancreas

2005
Skip Viragh Career Development Award
William G. Hawkins, MD
Washington University in St. Louis
Assessing the ability of regulatory T-cell depletion to augment xenogeneic DNA vaccination against mesothelin as a method to overcome immunologic tolerance in a murine model of pancreas cancer

Dr. Laurence A. Mack and Roselle Mack Memorial Career Development Award
Sunil R. Hingorani, MD, PhD
Fred Hutchinson Cancer Research Center
The Cell-of-Origin in Pancreatic Cancer

Career Development Award
Mircea Ivan, MD, PhD
Tufts University
Exploring hypoxia resistance in pancreatic tumors

Samuel Stroum Young Investigator Award - PanCAN-ASCO Award
Aram Hezel, MD
Dana-Farber Cancer Institute
Novel Therapeutic Antibodies for Pancreatic Ductal Adenocarcinoma

2004
Career Development Award
Anirban Maitra, MD
Johns Hopkins Medical Institutions
Notch Signaling in Pancreas Cancer

Samuel Stroum Young Investigator Award - PanCAN-ASCO Award
David S. Hong, MD
MD Anderson Cancer Center
SRC Kinase Inhibition with BMS-354825 in Pancreatic Cancer Models

2003
Career Development Award
C. Max Schmidt, MD, PhD
Indiana University
The Chemopreventive Role of Cyclooxygenase Inhibitors in Pancreatic Tumorigenesis

Career Development Award
David Tuveson, MD, PhD
University of Pennsylvania
Tumor suppressor gene loss of heterozygosity for the generation of a murine model of ductal pancreatic cancer

Career Development Award - PanCAN-ASCO Award
Andrew Ko, MD
University of California, San Francisco
Detection, Analysis, and Significance of Micrometastases in Pancreatic Cancer

Samuel Stroum Young Investigator Award - PanCAN-ASCO Award
Christopher Cogle, MD
University of Florida
Defining the Hemangioblast in Tumor Neoangiogenesis