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2008 Pancreatic Cancer Action Network Research Grants
The Pancreatic Cancer Action Network combines its push for increased federal research funding with direct research support of Fellowships/Young Investigator Awards, Career Development Awards, and Pilot Grants for pancreatic cancer research through a peer-reviewed grant system.
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Fellowship Award: One-year grant totaling $45,000 that is awarded to a postdoctoral or clinical research fellow at an academic facility, teaching hospital or research institution who is sponsored by a mentor. The intent of the award is to attract young scientists to a career in pancreatic cancer research.
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Career Development Award: Two-year grants totaling $100,000 per award that are provided to junior faculty at academic and medical institutions. The intent of these grants is to support and encourage young scientists to establish a career path in the field of pancreatic cancer research.
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Pilot Grant: Two-year grants totaling $100,000 per award that support innovative research in pancreatic cancer. This research may be basic, translational, or clinical in nature. Particular consideration is given to projects that are non-duplicative and have the potential for national application.
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In 2008, 11 grants were awarded, totaling $1,045,000 in funding. This year’s research portfolio includes one Fellowship, six Career Development Awards, and four Pilot Grants. Collectively, these grants support junior and senior scientists and provide funding for research in diverse fields of inquiry, including: the origin and causes of pancreatic cancer; the biology of the disease, including underlying physiological and biochemical processes; discoveries in detection, staging and diagnosis; and novel therapeutic strategies.
Since introducing the Research Grants Program in 2003, the Pancreatic Cancer
Action Network has provided over $3.7 million in funding for research. This
includes six Fellowship/Young Investigator Awards, 23 Career Development
Awards, and nine Pilot Grants.
Fellowship Award
Samuel Stroum - Pancreatic Cancer Action Network – AACR Fellowship
Ken-Tye Yong, PhD
State University of New York, Buffalo, NY
Engineering Multimodal Targeted Probes for Pancreatic Cancer
Detection
Click
here to download Dr. Yong's Grant Snapshot
As a postdoctoral student, Dr. Yong’s advisors have been very instrumental
in inspiring his interest in pancreatic cancer research. His specific
interests are to engineer ultrasensitive materials capable of early
diagnosis to help improve patient survival.
The funded research focuses on the development of quantum dots (QDs)
with enhanced illumination and magnetic features to enable early
diagnosis of pancreatic cancer. QDs are luminescent nanoparticles
that can serve as probes for imaging. In previous research, Dr.
Yong developed QDs that can selectively visualize pancreatic cancerous
cells in vitro (laboratory). However, for in vivo (in the body)
application, these prototype QDs lack the properties as a diagnostic
tool. Building on his previous research, new QDs-based nanoparticles
will be developed which integrate multiple imaging abilities combining
optical imaging and magnetic resonance imaging (MRI). The integration
of these two imaging modalities will be used to develop a novel
nanoparticle system to explore detection of human pancreatic cancer
in an animal model. The study results are expected to pave the way
for the development of novel contrast agents for optical imaging
and MRI, thereby enabling early diagnosis of pancreatic cancer.
Career Development Awards
Constance Williams - Pancreatic Cancer Action Network - AACR Career
Development Award
Marie-Christine Daniel, PhD
University of Maryland, Baltimore County, MD
Multifunctional Nanovectors for Pancreatic Cancer Therapy
Click
here to download Dr. Daniel's Grant Snapshot
After losing her mother from a rare cancer, Dr. Daniel chose to
devote her research to this field. She was struck by the aggressiveness
of pancreatic cancer and its low survival rate, and is interested
in contributing to efforts to improve treatment for this disease.
The funded research focuses on nanotechnology as a therapeutic strategy
for pancreatic cancer. Nanocarriers are devices with a size comparable
to biological entities such as proteins or viruses but are much
smaller than cells. Along with other properties, this confers upon
them distinct advantages over traditional small molecule approaches.
Among others, they increase blood circulation time compared to small
drugs; provide protection of active agents against enzymatic or
environmental degradation; and allow combination of several different
agents. Nanovectors are in general composed of three parts: a core
constituent material, a therapeutic and/or imaging payload, and
some biological surface modifiers that enable tumor targeting of
the nanoparticle dispersion. The objective of this study is to prepare
nanoparticles that combine multiple agents and to test the effectiveness
of such an entity against transformed pancreatic cell lines. Upon
the preferential entry of a nanovector into a cell, a very large
quantity of therapeutic agents will be delivered. This targeted
combination therapy is predicted to allow for a dramatic enhancement
in potency and efficacy in pancreatic cancer treatment along with
a decrease of the side effects.
Seena Magowitz - Pancreatic Cancer Action Network – AACR Career
Development Award
David Dawson, MD, PhD
University of California, Los Angeles, CA
Wnt Signaling in Pancreatic Cancer Progenitor Cells
Click
here to download Dr. Dawson's Grant Snapshot
As a cancer researcher and sub-specialty gastrointestinal pathologist,
Dr. Dawson is acutely aware of the aggressive biology of pancreatic
cancer and the poor prognosis for most patients with this devastating
disease. This awareness has propelled him to pursue research in
this area.
Each pancreatic tumor is made up of a mixed population of cells
that have varied biological properties. A very small percentage
of these cells, referred to as cancer stem cells, appear to be largely,
if not solely, responsible for the ability of the tumor to first
evolve and then grow in size, resist chemotherapy and spread elsewhere
in the body. Dr. Dawson’s research focuses on how these rare pancreatic
cancer stem cells differ from the majority of the cells that make
up any individual’s pancreatic tumor, and how these differences
might be responsible for the development and aggressiveness of pancreatic
cancer. Better understanding the biology of these pancreatic cancer
stem cells will facilitate the development of new strategies to
target them with drugs or by other means, and thus more effectively
treat pancreatic cancer.
Blum-Kovler - Pancreatic Cancer Action Network – AACR Career Development
Award
Joseph Michael Herman, MD
Johns Hopkins University School of Medicine, Baltimore, MD
Evaluation of Focused Radiation to Potentiate a Pancreatic GM-CSF
Vaccine
Click
here to download Dr. Herman's Grant Snapshot
Dr. Herman has devoted his career to pancreatic research in the
hope of improving the quality and quantity of life of patients with
this diagnosis. He is specifically interested in vaccine therapy
because it adds little toxicity to standard treatments. By combining
vaccine therapy with radiation and chemotherapy, survival and quality
of life can be improved for patients with pancreatic cancer.
The funded research builds on previous work to develop a novel pancreatic
vaccine, which is comprised of irradiated (killed) pancreatic cells,
that is administered under the skin to induce the body's immune
system to attack pancreatic cancer. In patients with resected pancreatic
cancer (pancreas tumor surgically removed), a combination of this
vaccine with chemotherapy and radiation has been found to improve
survival and result in less toxicity than traditional treatments.
Vaccine alone may not be adequate for patients with unresectable
and metastatic pancreatic cancer because the tumor is bulky and
it is hard for the vaccine to penetrate. However, the role of vaccine
therapy for these patients has not been sufficiently addressed.
The funded research more closely examines this role. Specifically,
it uses animal models with pancreatic cancer to test how focused
radiation may make the pancreatic vaccine work better and to determine
the optimal treatment combination. Single high dose stereotactic
(focused) radiation therapy prior to vaccination may be more effective,
cause less side effects and be more convenient than standard radiation
treatment (which consists of 25 daily treatments). It is hoped that
this unique translational mouse model can be used to determine how
to optimally combine radiation, vaccine, chemotherapy, and targeted
therapy for patients with unresectable, resectable, and metastatic
pancreatic cancer.
Skip Viragh - Pancreatic Cancer Action Network – AACR Career Development
Award
Hyunki Kim, PhD
The University of Alabama at Birmingham, AL
MRI to Monitor Early Pancreatic-Tumor Response to a Novel Triple
Therapy
Click
here to download Dr. Kim's Grant Snapshot
Dr. Kim joined the drug development program for pancreatic cancer
treatment at his school after realizing how few drugs were available
to treat pancreatic cancer patients. He is inspired to help fill
this void and develop new drug treatments.
Investigators in the University of Alabama at Birmingham (UAB) created
a new drug named TRA-8, which kills cancer cells without having
any bad effects on normal cells. TRA-8 has been very effective in
prolonging survival of mice having pancreatic cancer, especially
when combined with conventional drugs. Currently, TRA-8 combined
with gemcitabine has been tested with a limited number of pancreatic
cancer patients at UAB. However, not all patients are expected to
respond in the same way to the treatment. The aim of the funded
project is to develop a method to determine how each patient responds
to these drugs, using magnetic resonance imaging. The results from
the imaging method, which will be applied during treatment, will
enable treatment plans to be adjusted during therapy, thereby maximizing
the therapy efficacy for each individual patient. Plans are to develop
the imaging method using an animal model first, and then translate
it to human patients. This method will extend and even save many
pancreatic cancer patients by minimizing unnecessary treatments.
Laurie and Paul MacCaskill - Pancreatic Cancer Action Network –
AACR Career Development Award
Lorenzo F. Sempere, PhD
Dartmouth Medical School, Hanover, NH and Dartmouth-Hitchcock Medical
Center, Lebanon, NH
Role of MicroRNAs in Initiation and Progression of Pancreatic
Cancer
Click
here to download Dr. Sempere's Grant Snapshot
Last year, Dr. Sempere's close relative died of pancreatic cancer
within a month following diagnosis. Although she had experienced
some minor health issues associated with her diabetes, nothing suggested
cancer. Dr. Sempere's research is dedicated to her memory and to
the hope that his work may provide new tools for early detection
and treatment of this stubborn and aggressive disease.
The funded project will examine the role of microRNAs in pancreatic
cancer. microRNAs are a recently discovered class of unusual and
very short genes. They do not code for proteins and hence are referred
to as noncoding RNAs. microRNAs are thought to regulate key processes
that keep the cells at check and prevent them from developing cancer.
Recent reports have shown that there are changes in the levels of
microRNAs between normal and tumor tissues of patients suffering
from different types of cancer, including pancreatic cancer. The
funded study will use a special staining technique called in situ
hybridization to visualize exactly where changes of selected microRNAs
occur in the pancreas of mouse models that have been purposely designed
to develop pancreatic cancer. Since pancreatic tissue is composed
of different cell types and only some of these cells are susceptible
to develop cancer, it will be important to know if these microRNA
changes occur within the cancer-prone cells. If so, then, the study
will determine whether having too much or too little of a specific
microRNA affects the growth and survival properties of the pancreatic
cancer cells in vitro and in vivo.
Patty Boshell - Pancreatic Cancer Action Network – AACR Career Development
Award
Peter Storz, PhD
Mayo Clinic, Jacksonville, FL
Kinases Regulating Pancreatic Cancer Resistance to Chemotherapeutics
Click
here to download Dr. Storz's Grant Snapshot
Dr. Storz chose to focus his research on pancreatic cancer since
he recognized that it is the most aggressive cancer and requires
a more aggressive and innovative approach to improve patient outcomes.
His specific interest is in discovering new molecular targets for
the development of novel drugs that allow better response to chemotherapy
and prevent recurrence.
The funded project is designed to identify cellular signaling proteins
(kinases) that regulate resistance of pancreatic cancer cells to
chemotherapeutic agents. Such kinases may serve as potential drug
targets for pancreatic cancer therapy. A global approach will be
employed to uncover key enzymes and test if some of them could serve
as targets for novel therapeutics to decrease the resistance of
pancreatic cancer to chemotherapy drugs. Study results are expected
to contribute to the development of a pharmacologic strategy to
re-sensitize pancreatic tumor cells to conventional chemotherapeutic
drugs, thereby providing new avenues for therapeutic intervention
in this disease.
Pilot Grants
Randy Pausch, PhD - Pancreatic Cancer Action Network – AACR Pilot
Grant
Nabeel Bardeesy, PhD
Massachusetts General Hospital, Boston, MA
Molecular Markers of Drug Sensitivity in Pancreatic Cancer
Click
here to download Dr. Bardeesy's Grant Snapshot
Dr. Bardeesy’s interest in pancreatic cancer research developed
while pursuing his postdoctoral studies and was sparked by a fellow
student who had lost two family members to the disease. This experience
highlighted the urgency for an improved understanding of the biology
of the disease and the need to discover effective treatment options.
The funded project focuses on the development of improved approaches
to pancreatic cancer treatment. In other cancers, progress in treatment
has come from the observation that some patients respond to certain
therapies and that this response is due to specific genetic alterations
in the tumor cells. The importance of this discovery is that it
demonstrates that different drugs can be matched or “tailored” to
patients with these genetic changes who are most likely to benefit
from these treatments. Only about 10% of patients with pancreatic
ductal adenocarcinoma are responsive to targeted and conventional
therapeutics. This study plans to analyze the responsiveness of
cells derived from many different pancreatic cancer patients to
a large set of anti-cancer drugs and then compare the drug sensitivity
with the genetic features of the cancer to determine which features
predict drug responsiveness. Predictions will be tested using a
series of mouse models that resemble the human disease. Overall,
the study is expected to define distinct subgroups of pancreatic
ductal adenocarcinoma, provide new insights into cancer therapeutics,
and directly inform the design of refined clinical trials.
Pancreatic Cancer Action Network – AACR Pilot Grant
Dafna Bar-Sagi, PhD
New York University School of Medicine, New York, NY
Impact of Diet-Induced Hyperlipidemia on Pancreatic Inflammation
and Cancer
Click
here to download Dr. Bar-Sagi's Grant Snapshot
Dr. Bar-Sagi’s involvement in pancreatic cancer research resulted
from her interest in making a difference in understanding and curing
a disease for which things have been hopelessly the same for the
past few decades.
The funded project focuses on the relationship between high fat
diet-induced hyperlipidemia and the development of pancreatic cancer.
Hyperlipidemia is an excess of fatty substances called lipids, largely
cholesterol and triglycerides, in the blood. High fat diet and obesity
have been implicated in the etiology of chronic pancreatitis (inflammation
of the pancreas) and pancreatic cancer. However, the mechanistic
basis of this association remains unknown. The overall goal of the
project is to establish a mouse model and investigate this link.
The experimental design will take advantage of mice that have been
genetically engineered to develop hyperlipidemia following feeding
of a high fat diet. These mice will be employed to (1) characterize
the structural changes that the pancreas endures in response to
hyperlipidemia, and (2) assess the effects of hyperlipidemia on
pancreatic cancer development. By exploring the cause-and-effect
relationships between hyperlipidemia and pancreatic carcinogenesis,
these studies will provide new insights into the epidemiological
connection between obesity, high fat diet and pancreatic cancer.
Michael C. Sandler - Pancreatic Cancer Action Network – AACR Pilot
Grant
Matthias Hebrok, PhD
University of California, San Francisco, CA
NF-kB Signaling in PanIN Formation
Click
here to download Dr. Hebrok's Grant Snapshot
Dr. Hebrok became interested in pancreatic adenocarcinoma when one
of his colleagues at UCSF was diagnosed and eventually succumbed
to the disease. Witnessing the rapid decline in his colleagues health,
he felt that studying basic aspects of this disease with the intent
to gather novel information about potential therapeutic targets
was an important goal.
The funded project involves genetic experiments that explore the
role of NF-kB signaling in the progression of healthy pancreatic
epithelium (the cellular covering of the pancreas) to pre-cancerous
lesions. Pancreatic ductal adenocarcinoma (PDAC) develops through
a sequence of precancerous lesions termed “pancreatic intraepithelial
neoplasias” or PanINs. Recently, mouse models of PDAC have been
described that repeat in its development human PanIN progression.
However, because lesion formation in these mice occurs gradually
and the onset of specific stages is variable, the molecular requirements
for the different stages have been difficult to interpret. A rapid
and synchronized mouse model of PDAC precancerous lesions has been
developed using chemical induction of pancreatitis (inflammation
of the pancreas), which is frequently correlated with PDAC in humans.
The use of this model allows the role of specific pathways to be
efficiently determined in the earliest disease stages. Preliminary
data using this model show that NF-kB signaling, a pathway that
is involved in inflammation and cell proliferation and is highly
active in human pancreatitis and PDAC, plays a significant role
in lesion formation. This study aims is to better understand the
mechanisms by which this pathway guides the progression from normal
pancreatic cells to PanINs. Plans are to characterize the effects
of disrupting NF-kB signaling in PanIN progression and determine
which cells, in the transition from normal to disease state, possess
active NF-kB signaling. Results are expected to provide the field
with important indications of the therapeutic and diagnostic possibilities
involving the NF-kB pathway.
Pancreatic Cancer Action Network – AACR Pilot Grant
Bin Liu, PhD
University of California, San Francisco, CA
Internalizing Human Antibodies Targeting Pancreatic Tumor Cells
In Situ
Click
here to download Dr. Liu's Grant Snapshot
Dr. Liu’s interest in pancreatic cancer research, and particularly
in developing novel anti-body based diagnostics and therapeutics,
was sparked by interactions with his colleagues who are treating
patients and studying the origin and development of the disease.
The funded project aims to identify internalizing human antibodies
that target pancreatic adenocarcinorma cells in situ in their natural
tissue microenvironment. Currently, there are very few human antibodies
that target pancreatic tumors and even fewer detect early stage
tumors. The study examines the following two key hypotheses: (1)
Pancreatic tumors, like other tumors, possess unique cell surface
molecules that distinguish tumors from non-neoplastic tissues; and
(2) A subset of these tumor cell surface molecules are internalizing,
and thus can be exploited for tumor-targeted intracellular payload
delivery. The methods and strategies used in this study are based
on precise procurement of staged tumor cells by laser capture microdissection
to select internalizing human antibodies that target pancreatic
cells in situ. These novel antibodies, which are human
in sequence, can be used in the future to develop noninvasive imaging-based
strategies for early pancreatic tumor detection and targeted therapeutics
based on tumor-specific intracellular drug delivery.
For
a listing of our past PanCAN Grant recipients, please click
here.
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