AACR Career Development Awards are open to junior faculty at an academic or medical institution who completed postdoctoral studies or clinical fellowships no more than three years prior to the start of the grant term. The Awards provide two-year grants of $50,000 per year for direct research expenses and salary support.
Applications open in the Fall each year.
2008-2010 AACR-Aflac, Incorporated Career Development Award for Pediatric Cancer Research
Charles G. Mullighan, M.D.
St. Jude Children's Research Hospital, Memphis, TN
Project: Genomic Analysis of BCR-ABL1 Pediatric Acute Lymphoblastic Leukemia
"My research will use several complementary genomic approaches in parallel with in vivo modeling to identify the genomic abnormalities underlying BCR-ABL1 positive acute lymphoblastic leukemia (ALL). ALL is the commonest pediatric malignancy, and while most patients are cured, several ALL subtypes, such as BCR-ABL1 ALL, have a poor prognosis. BCR-ABL1 is also a hallmark of chronic myeloid leukemia (CML) and the reasons why CML and BCR-ABL1 ALL are so strikingly different in clinical features and outcome have been poorly understood. I recently performed genome-wide analysis of DNA copy number abnormalities in acute lymphoblastic leukemia and chronic myeloid leukemia using high-resolution single nucleotide polymorphism microarrays and found a high frequency of recurring abnormalities in genes regulating a variety of cellular pathways, most notably B lymphoid development in over 40% of B-lineage ALL. The genes involved include the transcription factors PAX5, EBF1 and IKZF1 (Ikaros). Notably, IKZF1 deletions were a near-obligate feature of BCR-ABL1 ALL, and were also observed at the progression of CML to lymphoid blast crisis. This suggests that alteration of Ikaros is a key event in the pathogenesis of BCR-ABL1 lymphoid leukemia. This study will use ultra-high resolution CGH microarrays to determine the nature and frequency of genomic abnormalities in ALL, and will complement this with genome-wide analysis of cytosine methylation and exon array analysis to examine the effects of genomic abnormalities on the leukemic transcriptome. I will use transgenic and retrogenic mouse models to examine the influence of Ikzf1 deletion and the expression of dominant negative Ikzf1 isoforms on the development of BCR-ABL1 ALL. These studies promise to further extend these exciting advances in our knowledge of the pathogenesis of this problematic subtype of leukemia, and will potentially identify novel therapeutic targets. My work in leukemia genomics has been performed in the laboratory of my mentor, Dr James R. Downing, at St Jude Children's Research Hospital, and this AACR grant will provide crucial support as I establish my own research program."
2008-2010 AACR-FNAB Career Development Award for Translational Cancer Research
Tara A. Young, M.D., Ph.D.
University of California, Los Angeles, Los Angeles, CA
Project: High Resolution Cytogenetic Study of Archival Metastatic Choroidal Melanoma
The goal of Dr. Young's research is to determine if high-resolution, genome-wide patterns of cytogenetic aberration within archival, primary choroidal melanoma tissue from patients of known metastatic outcome can accurately predict metastatic risk. Choroidal melanoma, a cancer arising from within the eye, causes both blindness and death. Despite successful treatments for the eye, 50% of patients will die of metastasis, or spread of the cancer to other parts of the body. No treatment for this cancer has been shown to improve survival. High resolution DNA and RNA microarray analyses will be performed on archival primary choroidal melanoma tumor tissue provided by the Collaborative Ocular Melanoma tissue bank. These data will be integrated with extensive existing microarray information from patient biopsies performed at UCLA for which metastatic outcome is not yet known. Cluster analysis with respect to both monosomy 3 and clinical metastatic outcome will be performed to identify key over- and under-expressed genes for molecular studies of metastasis. The access to archival material from the Collaborative Ocular Melanoma tissue bank has the advantage of known long-term patient follow-up including extensive medical histories on these patients which include whether the patients developed cancer metastasis or not. Our research will establish the link between which molecular signatures correlate most highly with choroidal melanoma patients who ultimately develop metastatic disease. This information will be important for future patients who are diagnosed with this cancer. By knowing with greater accuracy which patients will develop metastasis, we can offer systemic therapies to help improve patient survival early in the course of the cancer. In addition, knowing the key molecular differences between patients with good-prognosis and poor-prognosis will help us learn more from a scientific level how these cancers cause metastasis. The ultimate goal of this research will be to help develop treatments and cures for patients with choroidal melanoma.
2008-2010 AACR-Genentech BioOncology Career Development Award for Cancer Research on the HER Family Pathway
Chonghui Cheng, M.D., Ph.D.
Northwestern University, Chicago, IL
Project: The Role of Alternative Splicing in HER2-Dependent Breast Cancer
"The research focus of our lab is to investigate the role of aberrant alternative splicing in the development of breast cancer. Alternative splicing is a process that produces multiple protein isoforms from a single gene through different combinations of variable exons. This process is an essential mechanism in gene regulation in mammals and is estimated to occur in 50-75% of the human genes. Aberrant alternative splicing has been documented in cancers for over a decade. However, the importance of alternative splicing in oncogenic transformation has been largely unexplored. We have recently found that alternative splicing of CD44 augments the action of the epidermal growth factor receptor (EGFR/HER) pathway and produces sustained oncogenic Ras/MAPK signaling resulting in stable changes in cell growth in vitro. The goal of this project is to investigate the importance of CD44 splice isoforms in Her2-dependent breast tumor progression in vivo. We hope that our research will identify new regulatory mechanisms in cancer pathogenesis that may facilitate the development of new strategies in cancer therapies, such as targeting splice isoforms. The AACR-Genentech BioOncology Career Development Award for Cancer Research on the HER Family Pathway will be of great help for me to conduct this project and establish my early scientific career."
2008-2010 AACR-Pancreatic Cancer Action Network Career Development Award, in memory of Patty Boshell
Peter Storz, Ph.D.
Mayo Clinic, Jacksonville, Jacoksonville, TN
Project: Kinase Regulating Pancreatic Cancer Resistance to Chemotherapeutics
"Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive form of cancer known to date with the lowest overall 5-year survival rate. PDAC is extremely resistant to conventional chemotherapies, and there is a desperate need to identify new targets for molecular therapeutics. The resistance to common chemotherapeutics in pancreatic cancer and PDAC cell lines is tightly linked to NF-kappaB activity. NF-kappaB is an inducible transcription factor which, dependent on the stimulus, is regulated by a variety of kinase-regulated signaling cascades. Our project is designed to identify kinases that regulate resistance of pancreatic cancer cells to chemotherapeutic agents. Such kinases may serve as potential drug targets for pancreatic cancer therapy. We will employ a global approach to uncover these key enzymes and test if some of them could serve as targets for novel therapeutics to decrease the resistance of pancreatic cancer to chemotherapeutic agents. Once these kinases are identified we will screen compound libraries for specific inhibitors and test if they affect PDAC resistance to chemotherapeutics. The AACR-Pancreatic Cancer Action Network Career Development Award for Pancreatic Cancer research will allow us to identify kinases that may serve as potential drug targets for pancreatic cancer therapy and contribute to develop a strategy to re-sensitize pancreatic tumor cells to conventional chemotherapeutic agents."
2008-2010 AACR-Pancreatic Cancer Action Network Career Development Award, in honor of Laurie and Paul MacCaskill
Lorenzo F. Sempere, Ph.D.
Dartmouth University, Hanover, NH
Project: Role of microRNAs in Initiation and Progression of Pancreatic Cancer
"MicroRNAs (miRNAs) are a recently-discovered class of short non-coding RNA genes, which act as post-transcriptional negative regulators of gene expression. miRNA-mediated regulation of tumorigenesis is emerging as a new paradigm in the field of cancer biology. Specific miRNAs with suppressive and promoting functions have been shown to interact directly or indirectly with K-Ras, p53 and p16 pathways in physiological and pathological contexts. These pathways are pivotal for the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). This AACR-Pancreatic Cancer Action Network Career Development Award will be focused on the functional analysis of selected miRNAs aimed at assessing: 1) the onset and magnitude of miRNA expression changes by in situ hybridization analysis during disease progression in genetically-engineered mouse models of PDAC. 2) The contribution of individual miRNAs to pancreatic tumorigenesis by manipulating levels of miRNA expression/activity in murine pancreatic cancer cell lines and directly in the pancreas of these mouse models. Results from this grant should advance our understanding of the role of miRNAs in PDAC and potentially suggest new avenues for therapeutic intervention. Combinatorial therapy with current therapeutic agents and synthetic modulators of this novel class of regulatory RNAs may provide an effective strategy to increase patient response to treatment."
2008-2010 AACR-Pancreatic Cancer Action Network Career Development Award, in honor of the Blum-Kovler Family
Joseph M. Herman, M.D.
Johns Hopkins University, Baltimore, MD
Project: Evaluation of Focused Radiation to Potentiate a Pancreatic GM-CSF Vaccine
"Combining an allogeneic granulocyte-macrophage colony stimulating factor (GM-CSF) secreting pancreatic vaccine with chemoradiation improved survival in patients with resected pancreatic cancer. These results are encouraging for patients with resectable (20%) pancreatic cancer; however the GM-CSF vaccine has not been evaluated in the vast majority of patients (80%) who present with unresectable or metastatic pancreatic cancer. As a single treatment modality, the GM-CSF vaccine is not likely to have the potency required to overcome the obstacles of tumor burden and immune tolerance inherent in pancreatic tumors. In this proposal, I outline an animal model where focused (tumor plus a small margin) dose-escalated radiation is used to alter the pancreatic tumor environment to enhance the local and systemic response of the GM-CSF vaccine. I propose that this unique translational mouse model utilizing a unique small animal radiation research platform (SARRP) can be used to pre-clinically determine optimal combinations of high dose focused radiation, vaccine, chemotherapy, and targeted therapy for patients with unresectable, resectable (neoadjuvant), and metastatic pancreatic cancer. I am fortunate to have the support of nationally recognized experts in immunotherapy (Dr. Elizabeth Jaffee), radiation sensitization (Dr. Theodore DeWeese), and image guided animal radiation therapy (Dr. Wong). This grant will allow me to have the protected time in the lab necessary to optimize treatment with vaccine and radiation. Over the past three years I have cared for a number of patients with pancreatic cancer and I am convinced that translational research is crucial to improving their survival and quality of life."
2008-2010 AACR-Pancreatic Cancer Action Network Career Development Award, in memory of Skip Viragh
Hyunki Kim, Ph.D.
University of Alabama, Birmingham, AL
Project: MRI to Monitor Early Pancreatic-Tumor Response to a Novel Triple Therapy
"Early assessment of response to cancer therapy by non-invasive imaging will improve patient care by providing a mechanism for personalized medicine, increasing the predictability of a favorable outcome while saving morbidity due to unnecessary treatment. The goal of my research is to develop Magnetic Resonance Imaging biomarkers for early evaluation of pancreatic cancer therapy. The specific aim to accomplish this goal is to develop a diffusion-weighted MR imaging (DWI) and dynamic contrast-enhanced MR imaging (DCE-MRI) methods to evaluate early changes in orthotopic pancreatic tumor xenografts (adenocarcinoma) following a novel triple combined therapy (chemotherapy using TRA-8 plus gemcitabine, together with radiotherapy (XRT)) in SCID mice, and then to extend the MR imaging approach to a limited patient trial to further optimize DWI and DCE-MRI collection and analysis parameters, enabling this type of early evaluation in future clinical trials. Gemcitabine is now the first line treatment agent for pancreatic cancer patients, but anti-tumor efficacy by gemcitabine alone is modest. TRA-8 is a novel monoclonal antibody developed at UAB that induces a type of cell death called apoptosis, acting through a specific cellular target called death receptor 5 (DR5). The distinguishing feature of TRA-8 is the fact that no cytoxicity in any normal tissue has been reported up to date. But human pancreatic tumor cell lines showed a differential sensitivity to TRA-8-induced cytoxicity. While the mechanism of natural and/or acquired resistance for TRA-8 is still under investigation, this resistance can be overcome by the addition of chemotherapy and/or radiation. Non-invasive DWI is a well-studied MR imaging technique to quantify the increase of water diffusion caused by cell necrosis or apoptosis in tumors within 2~4 days for responding patients. DCE-MRI is also a non-invasive clinically approved imaging technique to measure early change (within 2~7 days) in the properties of microvasculature in tumor. Therefore, DWI and DCE-MRI are logical approaches to evaluate early therapeutic efficacy of the novel triple therapy. The MRI methods will be further developed and tested in limited clinical trials, and then can be more widely applied to assess early pancreatic-cancer response in patients."
2008-2010 AACR-Pancreatic Cancer Action Network Career Development Award, in memory of Seena Magowitz
David W. Dawson
University of California, Los Angeles, Los Angeles, CA
Project: Wnt Signaling in Pancreatic Cancer Progenitor Cells
"My research focuses on the intersecting roles of epigenetics and growth signaling pathways in the development and progression of pancreatic cancer. I have recently found that epigenetic alterations appear critical for the dysregulation of Wnt signaling in pancreatic adenocarcinoma. Wnt signaling promotes stem cell renewal and cell fate determination, and is implicated in cancer. Accumulating data support the concept that cancer stem-like/progenitor cells are largely responsible for chemoresistance, metastasis and tumor recurrence in a wide range of cancer types, including pancreatic adenocarcinoma. For this project I will investigate the role of Wnt signaling and early epigenetic alterations specifically in pancreatic cancer stem-like/progenitor cells. This research has the potential to advance our overall understanding of the mechanisms responsible for the highly aggressive behavior of pancreatic adenocarcinoma, as well as identify novel strategies or targets of therapeutic intervention for pancreatic cancer. I am honored to receive this AACR-Pancreatic Cancer Action Network Career Development Award in memory of Seena Magowitz. Both the opportunity for scientific collaboration and generous funding it provides will be invaluable during the critical phase of my career transition to an independent pancreatic cancer research investigator."
2008-2010 AACR-Pancreatic Cancer Action Network Career Development Award
Marie-Christine Daniel, Ph.D.
University of Maryland, Baltimore County, Baltimore, MD
Project: Multifunctional Nanovectors for Pancreatic Cancer Therapy
After losing her mother from a rare cancer, Dr. Daniel, classically trained as a synthetic inorganic chemist, chose to devote her research to this terrible disease. Struck by the aggressiveness of the pancreatic cancer and its very low survival rate, she decided to contribute to the efforts for improved treatment of 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 the 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 tumour targeting of the nanoparticle dispersion. The objective of this research is to prepare nanoparticles that combine multiple agents, for example, a cell-selective cytotoxin, an enhancer and a targeting moiety, 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. In vitro testing of these nanovectors will be performed in collaboration with an allied group in Experimental Therapeutics.
2008-2009 AACR Centennial Career Development Award for Childhood Cancer Research
Richard T. Williams
St. Jude Children's Research Hospital, Memphis, TN
Project: Resistance to Targeted BCR-ABL Kinase Inhibitor Therapy in Ph+ ALL
"The aim of my laboratory program is to develop and interrogate clinically-relevant murine models of selected high-risk pediatric leukemias with the goal to advance our knowledge of their biology and to develop novel therapeutic strategies. We previously found that the combination of BCR-ABL expression and inactivation of the Arf tumor suppressor gene is sufficient to generate rapidly lethal, transplantable murine pre-B cell leukemias in wild-type syngeneic, immune-competent recipient animals. This leukemia model closely recapitulates the clinical, biological and genetic features of human Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), an aggressive pre-B cell leukemia with a poor prognosis in children and adults. Further, we demonstrated that cell-extrinsic resistance of these BCR-ABL+, Arf-null leukemias to the first generation BCR-ABL kinase inhibitor, imatinib, is mediated in part through cytokine-dependent signaling within the host animals' hematopoietic micro-environment. Our future studies will focus on understanding the biological and genetic regulators of leukemogenesis in this Ph+ ALL model system. Further, we will use whole animal imaging approaches to understand the cellular and molecular basis of resistance to targeted therapies and develop novel therapeutic strategies to circumvent this resistance.
It is a great honor to receive the AACR Centennial Career Development Award for Childhood Cancer Research. This award will allow me to focus significant attention to this clinically-important problem of targeted therapeutic resistance. This research was initiated under the outstanding mentorship of Drs Charles Sherr and Martine Roussel at St Jude Children's Research Hospital during my pediatric Hematology & Oncology Fellowship."
2007-2009 AACR-Aflac, Incorporated Career Development Award for Pediatric Cancer Research
Robert Craig Castellino, M.D.
Emory University, Atlanta, GA
Project: WIP1, a therapeutic target in medulloblastoma
Dr. Castellino's research will investigate mechanisms by which the protein phosphatase WIP1 (PPM1D) contributes to development and progression of the most common malignant brain tumor of childhood, medulloblastoma. The intent of these studies is to develop small molecule inhibitors of WIP1 and provide pre-clinical evidence of the efficacy of inhibition of WIP1-associated signaling pathways for treatment of children with medulloblastoma.
The AACR-Aflac, Incorporated Career Development Award will allow Dr. Castellino to devote significant effort toward the understanding of pathogenesis and development of novel treatments for medulloblastoma, while he simultaneously continues to develop his career as a pediatric hematologist/oncologist. Dr. Castellino was initially inspired to pursue a career in medicine by his sister, Dr. Sharon M. Castellino, who currently practices pediatric hematology/oncology in Winston-Salem, NC. He was drawn to pediatric neuro-oncology as a consequence of his interactions with his medical school mentors, Drs. Gertrude B. Elion and Henry S. Friedman. He is especially indebted to his wife, Dr. Rita Nahta, a former AACR Research Fellowship recipient and current faculty member at Emory University, who constantly challenges him to develop his understanding of disease processes and to keep foremost in his mind the goal of improving treatment of children with cancer.
2007-2009 AACR-Genentech BioOncology Career Development Award for Cancer Research on Angiogenesis
Dakun Wang, M.D., Ph.D.
University of Rochester, Rochester, NY
Project: Biological function of VDU2 in pVHL-HIF-1-VEGF pathway and angiogenesis
"Our laboratory is interested in the identification of biochemical defects and characterization of the functions and signal pathways of these key players in kidney cancer. pVHL is a component of E3 ligase targeting hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) for ubiquitination and degradation. Mutations of pVHL gene found in clear cell renal cell carcinomas lead to loss of pVHL E3 ligase function, which results in accumulation of HIFs and overexpression of HIF-regulated genes, such as vascular endothelial growth factor (VEGF). This explains the highly vascularized phenotype of clear cell renal cell carcinomas. Compelling evidence suggests that these key mediators represent important targets for therapeutic interventions. Recently, we have identified two pVHL-interacting deubiquitinating enzymes, VDU1 and VDU2. These two VDUs are very intriguing deubiquitinating enzymes considering the role of pVHL in targeting molecules for ubiquitination and proteasomal degradation. They both can be ubiquitinated by pVHL, leading to their degradation. But VDU2, not VDU1, can interact with HIF-1alpha and deubiquitinate the ubiquitinated HIF-1alpha and salvage it from degradation, which results in the elevated VEGF production. This VDU2-pVHL regulated deubiquitination and ubiquitination processes might well provide important insights into the biochemical basis of pVHL-HIF-1alpha-VEGF-associated angiogenesis. The objectives of this proposal are to gain a better molecular understanding of the roles of VDU2 in pVHL-HIF-1alpha -VEGF pathway and angiogenesis, especially in the context of renal cell carcinomas. I am deeply honored to have been selected for this Career Development Award and am very grateful to the AACR and my colleagues at the urology research lab for their support. In particular, I'd like to thank my mentors, Drs. Edward M. Messing and Guan Wu, for their continuous encouragement, guidance, and support."
2007-2009 AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Carole and Bob Daly
Martin E. Fernandez-Zapico, M.D.
Mayo Clinic, Rochester, MN
Project: Characterization of the Hedgehog-interacting pathways in pancreatic cancer
"Pancreatic cancer has one of the poorest prognoses among human neoplasms. Besides surgical resection, which is only possible in less than 20% of the patients and is rarely curative, current therapies for pancreatic cancer rely on traditional non-specific cytotoxic agents with limited effects. Therefore, the need to develop effective therapies that target the signaling cascades involved in pancreatic carcinogenesis has never been greater. Interactions between these signaling pathways are crucial to the initiation, progression, and maintenance of the transformed phenotype. Thus, characterization of these signaling interactions is fundamental for the understanding of the complex and varied networks of events that lead to the development, and spread, of pancreatic tumors. For this purpose, we will focus on understanding the molecular interaction between Hedgehog, a new and important pancreatic carcinogenic cascade, and EGF, a well-characterized oncogenic signaling pathway in pancreatic cancer. In particular, we will determine the role of this signaling interaction in the growth of the pancreatic cancer cells. We are confident that the knowledge of Hedgehog signaling and its interacting pathways will help understand the complex network implicated in pancreatic tumorigenesis, as well as serve as a foundation for the development of new therapeutic approaches.
It is a great honor to receive the AACR-PanCAN Career Development Award for Pancreatic Cancer Research. I am convinced that this award will provide the support essential for my development as an independent investigator in this field of research. Moreover, it will certainly help to achieve our long-term goal, which is to improve the quality of life and develop treatments for pancreatic cancer patients derived from fundamental basic science knowledge. Finally, I am very grateful to my family and friends as well as colleagues at the Mayo Clinic for their support. In particular, I am truly indebted to my mentor, Dr. Raul Urrutia, for his encouragement and guidance throughout my career development in pancreatic cancer research."
2007-2009 AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Nancy Daly Riordan
Paul J. Grippo, Ph.D.
Northwestern University, Chicago, IL
Project: Evaluating Kras oncogene addiction in pancreatic precancer and cancer
Dr. Grippo will identify the addictive nature of the commonly mutated protein Kras in pancreatic cancer by employing a system that allows for regulated control of mutant Kras expression in mice. This project will also target at least three distinct cell types in the pancreas as a means of ascertaining which ones can derive pancreatic cancer. At the point mice develop precancerous lesions and/or pancreatic cancer, mutant Kras expression will be stopped to determine if these cells are addictive to the effects of mutant Kras expression and when, if at all, these cancer cells achieve a level of independence from mutant Kras. In addition, these findings will provide the rationale and timing for targeting certain cell types with compounds aimed at blocking the activity of mutant Kras. This work was initiated under the outstanding mentorship of Dr. Eric Sandgren, who was instrumental in motivating Dr. Grippo to pursue a career in pancreatic cancer research. Dr. Grippo continues to be encouraged in his research endeavors by patients and their family and friends.
2007-2009 AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Laurie and Paul MacCaskill
Kimberly A. Kelly, Ph.D.
Massachusetts General Hospital, Charlestown, MA
Project: Molecular imaging agents for early detection of pancreatic cancer
"My research will identify novel molecular markers and develop imaging probes for pancreatic ductal adenocarcinoma (PDAC), a disease with a 5-year survival rate of only 3%. 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 AACR-PanCAN Award is important since it will allow me to focus on these important studies and further this much needed research. Dr. Ralph Weissleder has been inspirational in the role of mentor, as I have learned much about molecular imaging and translating bench discoveries into clinically relevant agents with the potential for improved disease management and, hopefully, cures."
2007-2009 AACR-PanCAN Career Development Award for Pancreatic Cancer Research, in honor of Ralph H. Hruban, M.D.
Ben Z. Stanger, M.D., Ph.D.
University of Pennsylvania, Philadelphia, PA
Project: Investigation of the pancreatic "ductome"
Dr. Stanger's research will focus on the relationship between the embryonic development of the pancreas and pancreatic carcinogenesis. Specifically, he hopes to compare the signaling pathways that are active in the embryo with those that are active in a variety of premalignant lesions in the pancreas to better understand how cancer cells achieve their abnormal growth properties. "I was first inspired to work on pancreatic cancer following experiences I had as a medical student over ten years ago, caring for patients with this terrible disease. It has been frustrating to see such little progress made in the interim. I hope that the approach we are taking will allow us to identify early and critical events in pancreatic cancer formation that can be exploited for diagnosis and treatment."
2007-2009 AACR-PanCAN Career Development Award for Pancreatic Cancer Research
Huamin Wang, M.D., Ph.D.
UT M.D. Anderson Cancer Center, Houston, TX
Project: Functional study of hematopoietic progenitor Kinase-1 in pancreatic cancer
"Pancreatic cancer is the fourth leading cause of cancer death in the United States, preceded only by lung, colon, and breast cancers. The molecular mechanisms leading to pancreatic ductal cancer remain unclear even though multiple genetic alterations have been shown to be involved in this lethal disease in recent years. My laboratory will investigate the role of HPK1 in tumor invasion and metastasis as well as the underlying molecular mechanisms by which HPK1 regulates apoptosis, invasion, and/or metastasis in pancreatic cancer. Our study will not only provide novel information about how the HPK1 pathways affect the development and/or progression of pancreatic cancer, but also help to identify new biomarkers and therapeutic targets.
"I was inspired to pursue cancer research by many outstanding researchers at the University of Texas M. D. Anderson Cancer. I am especially grateful to Dr. James L. Abbruzzesse, Dr. Douglas Evans, Dr. Stanley R. Hamilton, and Dr. Craig Logsdon for their strong support. I am deeply honored to have been selected for the AACR-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."
2007-2009 AACR-PanCAN Career Development Award for Translational Pancreatic Cancer Research, in memory of Seena Magowitz
Rebekah R. White, M.D.
Duke University Medical Center, Durham, NC
Project: Prostate stem cell antigen: a specific target for pancreatic cancer therapy
Dr. White plans to investigate prostate stem cell antigen (PSCA), a GPI-anchored cell surface protein that is specifically overexpressed in pancreatic cancer and has been implicated as potential therapeutic target. As a surgical resident at Duke University, Dr. White engaged in clinical research on neoadjuvant therapy for pancreatic cancer under the mentorship of Dr. Douglas Tyler and spent 3 years working with Dr. Bruce Sullenger, whose laboratory is focused on the development of innovative nucleic acid therapeutics. During her residency and subsequent surgical oncology fellowship at Memorial Sloan-Kettering Cancer Center, she was motivated to make pancreatic cancer her primary clinical and research interest by the many patients with pancreatic cancer who could not be helped by surgery. Upon returning to Duke as faculty in summer 2007, she will resume research under the mentorship of Dr. Sullenger and plans 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.
2007-2009 AACR-Susan G. Komen for the Cure Career Development Award for Breast Cancer Research
Xiaochun Yu, M.D., Ph.D.
University of Michigan, Ann Arbor, MI
Project: USP11, a potential common regulator in breast tumorigenesis
"Our lab focuses on the mechanisms of BRCA1 in DNA damage response and tumorigenesis. BRCA1 gene (breast cancer susceptibility gene 1) is the first gene cloned as a breast cancer suppression gene. Cancer genetic studies demonstrate that mutations in the BRCA1 gene account for more than 50% of hereditary breast cancer, and carriers of BRCA1 mutations have a 40-80% risk of acquiring breast cancer early in their lifetime. Although biallelic BRCA1 mutations are rarely found in sporadic breast cancer, loss of BRCA1 expression has been shown in 30% - 60% sporadic breast cancer. It suggests that BRCA1 and its biological pathway may have key roles not only in familial breast cancer but also in sporadic breast cancer development.
"Ten years since the cloning of the BRCA1 gene, the biological function of BRCA1 is still elusive. In 2003, our research group demonstrated that C-terminus BRCT domain of BRCA1 gene product recognizes phospho-protein and may involve in DNA damage induced signal transduction. Following on this breakthrough finding, we identified a BRCA1 binding partner, CtIP. We have demonstrated that BRCA1/CtIP interaction is required for DNA damage response. Moreover, we recently identified a potential regulator in the BRCA1-dependent CtIP ubiquitination, namely USP11. Currently, we plan to analyze the function of USP11 in the BRCA1-dependent DNA damage response and in breast cancer prevention."