AACR Research Fellowships foster basic, translational, clinical, and epidemiological research by scientists at the beginning of their careers in the cancer field. They are open to Postdoctoral Fellows and Clinical Research Fellows at an academic facility, teaching hospital, or research institution who will be in the first, second, or third year of their postdoctoral training at the start of the fellowship term.
Fellowships support the salary and benefits of the Fellow, with partial funds permitted to be designated to direct research expenses.
2009-2010 AACR Anna D. Barker Fellowship in Basic Cancer Research
Sarah Talarico, Ph.D.
Fred Hutchinson Cancer Research Center, Seattle, WA
Project: H. pylori Adhesin Switching in Promoting Bacterial Evolution and Disease
"Helicobacter pylori is a bacteria, commonly acquired in childhood, that persistently infects the human stomach. While some people never develop any symptoms, H. pylori causes severe disease including ulcers and stomach cancer (the second-leading cause of cancer deaths worldwide) in some infected individuals. An estimated 63 percent of stomach cancer cases are due to H. pylori infection. There are genetic differences among strains of H. pylori that likely account for differences in disease development among those infected. Differences in H. pylori genes that encode adhesins, structures expressed on the surface of the bacteria and involved in attachment of the bacteria to the stomach tissue, are especially likely to impact disease development because these structures have direct interactions with the infected patient's cells. The H. pylori SabA adhesin binds to a receptor that is present on inflamed stomach tissue. I have discovered that H. pylori have at least three different ways to vary the expression of the SabA adhesin using genetic switching events. I think this means that the ability to adapt the amount and types of adhesin protein expressed on the surface helps the bacteria successfully maintain infection while at the same time eliciting disease causing inflammation, even as environmental pressures in the human stomach change. This project will test this hypothesis. To better understand the role of genetic variability of adhesin genes as a mechanism for the bacteria to control its interactions with the host cells, the effects of different types of genetic switching events on the presence and amount of the SabA adhesin on the bacterial surface will be determined. I will also investigate whether the ability to use one, none, or all three switching mechanisms affects the bacteria's ability to promote persistent infection and inflammation. In mice engineered to express low or high levels of the host receptor, I will perform a competitive infection experiment between engineered bacterial strains that differ in the SabA adhesin gene switching that they can undergo and determine which regulatory mechanisms allow better survival and increased inflammation. Study of the contribution of genetic differences of H. pylori adhesins to the differences in ability to establish an infection and cause disease will further our understanding of the mechanisms that are involved in development of stomach cancer. A better understanding of this will aid in the development of new prevention and treatment strategies to reduce the disease burden of stomach cancer resulting from H. pylori infection. Receiving the Anna D. Barker Fellowship in Basic Cancer Research is a tremendous honor for me and an important first step in establishing my career as a researcher investigating the microbial factors involved in the development of cancer."
2009-2010 AACR-Astellas USA Foundation Fellowship in Basic Cancer Research
Nesrine I. Affara, Ph.D.
University of California, San Francisco, San Francisco, CA
Project: Manipulating Adaptive-innate Immune Cell Crosstalks During Carcinogenesis
"We and others have demonstrated that cancer development is regulated not only by genetic changes in would-be neoplastic cells but also by changes in adjacent stroma that confer a growth advantage to evolving tumors. We have utilized a mouse model of epithelial carcinogenesis (i.e., K14-HPV16 transgenic mice) to evaluate the functional significance of immune cells that infiltrate stroma of early neoplastic tissue. Our studies have revealed that activation of B lymphocytes in peripheral lymphoid tissues, humoral immunity and deposition of antigen-specific immunoglobulins (IgG) greatly potentiate squamous carcinogenesis by initiating a chronic inflammatory microenvironment and enhancing development of angiogenic vasculature. To identify molecular mechanisms regulated by B cells and humoral immunity that enhance cancer development by regulating infiltration of neoplastic tissue by immune cells, the major goals of my research are to: 1) determine functional consequences of Fc receptor (FcγR)-deficiency on chronic inflammation, tissue remodeling, angiogenesis and neoplastic progression in HPV16 mice; 2) determine if mast cells represent the functionally significant FcγR-expressing innate immune cell required for mediating B cell-induced chronic inflammation; and 3) evaluate FcγR-induced signaling pathways as therapeutic targets for inhibiting protumor properties of FcγR-expressing leukocytes. These studies will reveal the functional significance of FcγR signaling as a mediator of cancer development, and will determine which FcγR-expressing cells represent tractable targets for anti-cancer therapy. My interest in understanding important paracrine-mediated molecular response pathways significant for tumor-stromal cell interaction and cancer development led me to join Dr. Coussens laboratory at UCSF as her studies have fostered a paradigm shift in thinking regarding protumor immunity and cancer development."
2009-2010 AACR-Astellas USA Foundation Fellowship in Basic Cancer Research
Cornelius Miething, M.D.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Project: Identification of Novel Tumor Suppressors in B-cell Lymphomas by in-vivo RNAi
"Four percent of all new cancers in the US in 2007 fell into the group of Non-Hodgkin Lymphomas, and about one third of these belong to the group of diffuse large-cell B-cell lymphomas (DLCBL). Although the outcome for this type of cancer has improved over the last 15 years, the five-year survival rate especially for high-risk and elderly patients is still dismally low.
The development of novel techniques such as Single Nucleotide Polymorphism (SNP)- or chromosomal genomic hybridization (CGH)-arrays has been an important step towards identifying genetic aberrations underlying DLCBL, allowing the detection of small chromosomal changes in tumor cells which escape classical cytogenetics. In some cases, several tumors share a distinct loss of genetic information, supporting the notion that these deleted areas may contain genes important to suppress tumor development. But since the stretches of deleted DNA still may contain up to hundreds of genes, assessing the contribution of individual genes to tumor development remains difficult.
We propose to employ stable RNA interference (RNAi) to screen for genes involved in lymphoma development in an in-vivo mouse model of B-lymphomagenesis. RNAi allows us to specifically inactivate genes by retrovirally introducing so called short hairpin RNAs (shRNAs) complementary to the gene´s mRNA into hematopoietic stem cells. If the shRNA targets a gene whose loss contributes to tumorigenesis, the shRNA-carrying cells will enrich, and mice receiving cells infected with that shRNA will develop tumors more rapidly than controls. The shRNAs (and thus the relevant genes) can be recovered from the tumor DNA and identified by sequencing. From published data, we have assembled a list of frequently deleted chromosomal regions in DLCBL identified by SNP- or CGH-analysis, and have created a library of shRNAs targeting the genes located in these regions. Initially, we will functionally test these shRNAs for their ability to accelerate lymphomagenesis. Subsequently, we will follow up on genes that score in the screen and investigate how they accelerate tumor development.
I am honored and thankful to receive the AACR-Astellas USA Foundation Fellowship in Basic Cancer Research, which will provide valuable support for this project. We hope that the identification of novel tumor suppressor genes and the corresponding pathways will help to develop new treatments for this type of blood cancer. Also, it may allow to establish new prognostic factors and thus be useful to determine which patients will profit from more aggressive therapies."
2009-2010 AACR-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research
Salvatore J. Coniglio, Ph.D.
Albert Einstein College of Medicine of Yeshiva University, New York, NY
Project: Mechanisms of Microglia-Stimulated Glioblastoma Invasion
"Despite our increased understanding of the biology of high-grade brain tumors (grade IV glioma) over the last decade, it remains one of the deadliest cancers. Cells from the glioma tumor are highly motile allowing them invade adjacent normal brain tissue, making complete surgical removal nearly impossible. This is evident as the tumor generally reoccurs within a short period of time, near the margin of where the surgery was performed. Therefore, interfering with the motile properties of glioma cells would be a very effective strategy for treating this disease. An emerging theme in cancer biology is that tumors seem to require other non-tumor cells at late stages of the disease in order to become fully malignant. Work from our laboratory and collaborators have shown that a certain class of these non-tumor cells, called macrophages, are required for breast cancer cells to invade and metastasize to the lung. These findings were confirmed using state-of-the-art imaging techniques pioneered in our laboratory, where we can observe cells interacting with each other in a living mouse. We hypothesize that this malignant collaboration between tumor cells and macrophages may also apply to other cancer types, including gliomas. Indeed, examination of sections isolated from brain tumors show extensive microglia (the cell equivalent of macrophages in the brain) infiltration into the tumor at the invasive edges. In addition, there are several very recent studies which suggest that killing off the microglia in this context limits the amount of glioma invasion. In this proposal, we wish to identify the molecules which are responsible for mediating the communication between glioma cells and microglia. It is our hope that this work will lead to discovery of therapeutic targets both in the glioma cells and in the macrophage population (a heretofore unexploited compartment for cancer therapy)."
2009-2010 AACR-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research
Grace Suh, M.D.
UT M. D. Anderson Cancer Center, Houston, TX
Project: Inhibition of Autophagy in ARHI-Induced Model of Ovarian Cancer Dormancy
"Almost everyone with advanced ovarian cancer will eventually succumb to recurrent disease. The development of recurrence after a disease-free interval underlies the concept of tumor dormancy. One proposed mechanism for tumor dormancy involves autophagy, an adaptive process by which cells maintain survival during periods of nutrient or oxygen deprivation via self-digestion. Over the past decade, our laboratory has characterized ARHI, a tumor suppressor gene found to be down-regulated in over 60% of primary epithelial ovarian cancers and up-regulated in over 90% of recurrent tumors. We have discovered that ARHI plays an important role in autophagy. Furthermore, we have found a link between autophagy and tumor dormancy and have developed the first model of ovarian cancer dormancy. My proposal is to use this dormancy model to test the hypothesis that ovarian cancer cells escape cell death during chemotherapy by undergoing autophagy, and that inhibition of autophagy with chloroquine, a known inhibitor of autophagy, will enhance cell death and eliminate dormant cells. Promising results from these proposed studies would support the novel use of chloroquine, a safe and cost-effective agent, to augment the effectiveness of current chemotherapy, to eradicate dormant cancer cells, and to cure more women with advanced ovarian cancer."
2009-2010 AACR-Astellas USA Foundation Fellowship in Clinical/Translational Cancer Research
Akash Patnaik, M.D., Ph.D.
Beth Israel Deaconess Medical Center, Boston, MA
Project: Targeting Obesity and Prostate Cancer in Autochthonous Mouse Models
"Prostate cancer remains the third leading cause of cancer-related deaths in American men. The treatment options for advanced prostate cancer are limited, resulting in tremendous human suffering and high death rate. During my residency and early clinical fellowship training, I had the misfortune of witnessing the progressive downhill course of my maternal uncle, who recently died of rapidly progressive, castrate-resistant, metastatic prostate cancer. Throughout his suffering, I questioned why there was no "druggable target" to treat advanced prostate cancer. It was the beginning of an endless journey of asking more questions than there were answers available. This unfortunate loss, along with my experience as a young physician-scientist in Oncology caring for patients with advanced, castrate-resistant prostate cancer, inspired me to return to the laboratory bench to develop novel targeted therapies for this devastating disease.
Human cancers typically arise from a single cell, which undergoes multiple genetic insults over time. These genetic defects confer a significant growth and survival advantage, resulting in the production of a detectable cancer. The abnormal cancer cells also receive distant signals from hormones, which amplify the abnormal growth of the cancer. An understanding of the genetic and metabolic abnormalities that drive prostate cancer will enable us to develop novel therapies. Population studies suggest that obesity may contribute to prostate cancer progression and increased death-rate from the disease. We propose that obesity contributes to prostate cancer progression via increased blood concentrations of insulin and decreased blood concentrations of adiponectin, respectively. To elucidate the mechanistic relationship between obesity and prostate cancer progression, we will utilize mice genetically predisposed to develop prostate cancer. We will feed the mice a high-calorie diet to induce obesity and its associated metabolic abnormalities, and assess for prostate cancer development and progression. We will test new drugs that target both the abnormal proteins within the cell and the insulin/adiponectin pathways, singly or in combination, for ability to eradicate prostate cancer in mice. These preclinical studies will help us select patients for clinical trials that are most likely to respond to a given therapy. Using the Physician Health Study and the Health Professional Study databases, we will correlate signaling pathway activation in cancerous tissue with clinical information, to further understand the relationship between obesity and prostate cancer. Taken together, the above approaches will lead to the identification of cellular and hormonal triggers for prostate cancer, and contribute to the development of new, personalized therapies.
As I start to think about my first academic position following postdoctoral fellowship, grant support will be paramount in ensuring adequate protected research time to successfully carry out my research. I am honored to receive the 2009 AACR-Astellas USA Foundation Fellowship in Clinical/Translational Cancer Research. I believe that the outstanding environment in the Cantley laboratory, Beth Israel Deaconess Medical Center Prostate Cancer group and the Harvard Medical School communities, along with the AACR-Astellas USA Foundation Fellowship in Clinical/Translational Cancer Research will provide the support necessary to nurture my growth as an independently funded physician-scientist. I anticipate that what I observe at the bedside will generate new translational ideas in the laboratory, and what I learn in the laboratory will enable me to provide novel therapeutic options for patients, thus advancing the field."
2009-2011 AACR-AstraZeneca Fellowship for Translational Lung Cancer Research
Wei Lin, M.D.
UT M. D. Anderson Cancer Center, Houston, TX
Project: CXCL12/CXCR4 Axis in Tumor-Stroma Interaction in Metastatic Lung Cancer
"Most lung cancer patients die from metastatic disease, with a less than 5 percent chance of living beyond five years. Even among patients with early stage disease, more than one third will ultimately succumb to metastasis. Current therapies for metastatic lung cancer are palliative and are not based on an understanding of the biology of metastasis. Therefore, development of effective therapies depends on a deeper understanding of lung cancer metastasis.
Our laboratory has developed a mouse model of metastatic lung adenocarcinoma harboring a latent, somatically-activated Kras allele and a mutant p53 allele, and has derived cell lines from these mice with high and low metastatic potentials specifically to study this complex process. In tumors grown from subcutaneous injections of these cell lines, I have found that the metastatic cell line expressed higher levels of the chemokine CXCL12, recruited greater numbers of regulatory T cells, and demonstrated mesenchymal markers consistent with epithelial-mesenchymal transition (EMT), indicating that tumor-stroma interaction promotes metastasis. Based on these preliminary findings, I hypothesize that metastatic lung adenocarcinoma cells recruit inflammatory cells by CXCL12/CXCR4 signaling, and that the microenvironment created by infiltrating inflammatory cells induce tumor cells to undergo EMT and metastasize. To test this hypothesis, I will block CXCL12/CXCR4 signaling in the subcutaneous tumors by genetic suppression of chemokine CXCL12 expression with shRNA in the metastatic cancer cells, and by pharmacological inhibition with the CXCR4 antagonist AMD3100. I will evaluate the effect of this signaling blockade on inflammatory cell recruitment, EMT, and systemic metastasis from the subcutaneous tumors.
If inflammatory cell recruitment via CXCL12/CXCL4 signaling is an initiating and essential event in metastasis, then inhibiting this chemokine axis can be a novel strategy in treating metastatic lung cancer. The CXCR4 inhibitor AMD3100 is clinically available and can be readily translated as new therapy."
2009-2010 AACR-Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research
Jenna D. Goldberg, M.D.
Memorial Sloan-Kettering Cancer Center, New York, NY
Project: Post-transplant Administration of Interleukin-7
"Allogeneic hematopoietic stem cell transplants are integral to the treatment of hematologic malignancies. For some patients, they can offer the only curative therapy through the infusion of a tumor-free graft and/or a graft versus tumor effect. Following an allogeneic transplant there is a variable period of immunodeficiency. During this period of time, post transplant patients are subject to significant morbidity and mortality through development of infections. Multiple factors can delay immune reconstitution post allogeneic transplant including older age, T cell depletion and development of graft versus host disease. Dr. Marcel van den Brink's laboratory at Memorial Sloan-Kettering Cancer Center has identified interleukin-7 as an agent which, in mouse models, can enhance thymopoiesis as well as promote peripheral T cell expansion without causing GVHD. Based upon these promising preclinical data we have started a phase I clinical trial to test the administration of IL-7 in patients who are post T cell depleted allogeneic transplant for non-lymphoid malignancies. The primary objectives of the phase I study are to determine the safety and toxicity of IL-7 in this patient population. In addition, since IL-7 is a biological rather than a cytotoxic agent, our secondary objectives will include the determination of the activity of rhIL-7 on T cell reconstitution and an assessment of allo-HSCT specific complications. We hypothesize that administration of IL-7 will promote T cell reconstitution and decrease the treatment-related morbidity and mortality following allogeneic HSCT. I am truly honored to be awarded the 2009 AACR-Bristol Myers Squibb Oncology Fellowship in Clinical Cancer Research. This award will be an invaluable stepping stone for the development of my career in clinical research in the field of bone marrow transplantation. I would like to thank my primary mentor, Dr. Miguel-Angel Perales, for his continuing guidance and encouragement and the allogeneic transplant service at MSKCC for their support."
2009-2011 AACR-Genentech BioOncology Fellowship for Cancer Research on the HER Family Pathway
Marcia Campbell, Ph.D.
University of California, San Francisco, San Francisco, CA
Project: Towards a Druggable HER3; a Structure, Function and Signaling Analysis
"Approximately 25 percent of breast cancers are characterized by amplification of the Human Epidermal Growth Factor Receptor-2 (HER2) gene and two decades of evidence strongly implicates HER2 in the pathogenesis of this disease. This identifies HER2 as an Achilles' heel and suggests that drugs that can be designed to inactivate HER2 would be highly effective and may eradicate this disease.
However, scientific progress in recent years shows that HER2 does not function alone, rather it functions cooperatively with its equally important partner HER3 and it is the HER2-HER3 dimer that drives this disease. The current drugs are only weakly able to inhibit the HER2-HER3 dimer and advances in understanding how the HER2-HER3 dimer functions should allow the development of a new generation of effective drugs.
Based on the most recent scientific evidence, we have developed hypotheses regarding how the HER2-HER3 dimer can be inactivated. We think there is a particular conformation of HER3 that is most important, yet has been overlooked. We also think the kinase domain of HER3, which has previously been thought to be unimportant, is actually critically important in the HER2-HER3 complex. We are going to test these hypotheses using mutant forms of HER3 that will allow us to identify which conformations are important as well as study the kinase domain to identify regions critical to HER2- amplified tumorigenesis. These data will be used in future research to assist us in developing a prototype antibody drug to test whether the HER2-HER3 complex can be effectively disrupted by this type of drug.
It is an honor to be receiving the AACR-Genentech BioOncology Fellowship for Cancer Research on the HER Family Pathway. This award will allow me to carry out research in the field of HER family signaling in breast cancer that promises to provide important insights into breast cancer while at the same time allowing me to develop as a scientist and acquire the skills necessary to make important advances in the field. I am extremely grateful to my previous supervisor, Dr. Susan Andrew, and my current supervisor, Dr. Mark Moasser, for their continuous support and mentorship that has been critical in my development as a scientist."
2009-2010 Pancreatic Cancer Action Network-AACR Fellowship, in memory of Ruth Fredman Cernea
Philippe Foubert, Ph.D.
University of California, San Diego, San Diego, CA
Project: Role of Inflammation in Pancreatic Cancer
"Pancreatic cancer is a devastating disease, with an overall five-year survival rate below 1 percent. Improvement of our understanding of the molecular basis of pancreatic cancer is needed to develop novel therapies to treat this deadly disease.
Recent research has shown that tumor growth and spread can be accompanied by a progressive accumulation of macrophages that stimulate tumor growth and inhibit anti-tumor immunity. The means by which pancreatic tumors recruit macrophages and suppress the immune system remain unclear. In my research, I have found that macrophages accumulate in pancreatic tumors and suppress anti-tumor immunity by preventing dendritic cell (DC) maturation. Dendritic cells are key components of the immune system that instruct killer T cells to attack tumor cells. The immature DCs in pancreatic tumors suppress killer cell activation and thereby allow tumor growth.
In my fellowship project, I will analyze the molecular mechanisms by which macrophages suppress antitumor immunity during pancreatic cancer progression. I will determine how tumor macrophages inhibit dendritic cell maturation. To do so, I will study infiltration of macrophages and dendritic cells into tumors and draining lymph nodes from mice with pancreatic adenocarcinomas. I will compare these events in normal mice and mice with mutations that suppress macrophage infiltration. I will also study the effects of drugs that block macrophage infiltration and maturation. Using these model systems, I will identify the molecular signals produced by macrophages that inhibit dendritic cell maturation and/or trafficking. Finally, I will investigate the relationship between macrophages and mature and immature dendritic cells in human pancreatic tumor specimens.
This study could provide new insight into the mechanisms which account for immunosuppression and then lead to the design of new therapeutic targets against pancreatic cancer progression and metastasis.
In addition to expressing my gratitude to the AACR for this Pancreatic Cancer Action Network-AACR Fellowship, I would like to thank my previous mentor, Pr. Gérard Tobelem, as well as my current mentor, Dr. Judith Varner, for their guidance, enthusiastic support of my interdisciplinary research interests, and continued development as a scientist.
The AACR fellowship will provide valuable support for completing these studies and for building a strong foundation as a cancer researcher to pursue future scientific interests."
2009-2010 Pancreatic Cancer Action Network-AACR Fellowship, in memory of Samuel Stroum
Eric W. Humke, M.D., Ph.D.
Stanford University, Stanford, CA
Project: A Novel Paracrine Hedgehog Signaling Loop in Pancreatic Adenocarcinoma
"Pancreatic cancer is the fourth most common malignancy in the United States. The failure of current therapies is underscored by the fact that the diagnosis and death rates are roughly equal. Surgical resection is the most effective treatment, but most patients have advanced stages when they are diagnosed. One growth pathway that is reactivated during the formation of pancreatic cancer is Hedgehog, a signal transduction cascade critical for development of the normal pancreas. Recent work reveals that the soluble Hedgehog ligand, Sonic Hedgehog (Shh), is released from pancreatic cancer cells and is received by their surrounding non-cancerous support cells. The reception of Shh by the non-cancerous environment results in the release of a yet unidentified growth signal that feeds back to the pancreatic cancer, fueling it to grow even faster. This leads to many questions about how pancreatic cancer develops. What are the genetic mutations in pancreatic cancer that turn on Hedgehog, a signal normally important only in pancreas development? How does the released signal change the surrounding non-cancerous microenvironment? How does the non-cancerous tissue signal back to the cancer to allow it to grow even faster? These are all questions I hope to answer as part of my ongoing research on pancreatic cancer. If we understand the interplay between pancreatic cancer and its environment, we can develop novel therapies to target the non-cancerous environment to inhibit the signal for growth it is sending back to the pancreatic cancer. Defining the interplay between pancreas cancer and its surrounding stroma may be generally applicable to other tumors where aberrant Hedgehog pathway activation is implicated.
As a medical oncologist, I am driven to make discoveries in lab that will benefit the patients I see in clinic. Being awarded an AACR Pancreatic Cancer Fellowship is truly an honor and will allow me to continue my cancer research in the lab of Dr. Matthew Scott. This grant allows me to combine my passion for basic science with patient care and fosters my career development as a clinician-scientist in cancer research."
2009-2010 Pancreatic Cancer Action Network-AACR Fellowship
David T. Ting, M.D.
Massachusetts General Hospital, Boston, MA
Project: Characterizing Circulating Tumor Cells in Pancreatic Cancer
"Despite recent advances in cancer treatments, pancreatic cancer remains one of the most challenging malignancies to treat. The detection of circulating tumor cells (CTCs) in the blood of patients with solid malignancies is a promising diagnostic tool to help develop new strategies to combat this deadly disease. CTCs have been found in a number of different malignancies, and there have been encouraging studies indicating that the detection of CTCs can predict response to treatment and survival. However, the true nature of these cells remains a mystery. Many believe these cells are the critical cells that cause metastatic disease, which is most often the cause of cancer related death. Therefore, a better understanding of these cells through more detailed scientific investigation is needed. But, these studies have not been done due to limitations in current CTC capture technologies. A novel device named the CTC chip is able to capture higher numbers of purified CTCs that is not possible with current systems. This allows the opportunity to perform more sophisticated molecular analyses on these cells. We plan on first developing a mouse CTC chip for the capture of mouse CTCs in a pancreatic mouse model. The mouse model we are using has many of the genetic features found in human pancreatic cancer, which makes it a very powerful tool to evaluate how the genetics of the tumor affect CTCs. This will provide a robust system to best characterize pancreatic CTCs and a foundation to guide our analyses of CTCs captured from pancreatic cancer patients. We will then be able to evaluate the relevance of the relationships of tumor genetics to CTCs found in the mouse as they relate to our patients. With a simple blood draw, this technology provides a method to understand the biology of metastatic pancreatic cancer and evaluate how the tumor biology changes with therapies we provide our patients. These studies will be the first of their kind to demonstrate the potential the CTC chip has to provide insight into the nature of CTCs, guide our current therapies, and to create a platform for developing novel pancreatic cancer therapeutics. This AACR grant will provide me with the initial support needed to focus on this important research and lay the foundation for my development as a translational researcher and physician-scientist."