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Research Grants

The Cholangiocarcinoma Foundation Research Fellowship Program is aimed at supporting early career researchers focusing on studies in cholangiocarcinoma. The goal is to raise awareness about cholangiocarcinoma and inspire innovative, quality research.

2019 Research Fellowship Awards

2019 Andrea Marie Fuquay Award

Supported by the Daniel Fuquay family in honor of Andrea Marie Fuquay

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Immunosuppressive Myeloid Cells Facilitate Tumor Progression in cholangiocarcinoma

Researcher: Emilien Loueuillard PhD, Mayo Clinic

Amount: $50,000

"This proposal uses unique animal models of cancer to examine how the immune cells respond to bile duct cancer. The goal of our research is to understand how a type of immune cells in the liver, “termed myeloid derived suppressor cell” induces resistance to treatment against bile duct cancer, and facilitates the progression of this cancer. This information will help identify approaches to inhibit these cells, and provide a treatment strategy for this devastating human malignancy."

2019 Andrea Lynn Scott Award

Supported by Jason Scott & family in memory of Andrea Scott

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Targeting FGFR2 Signaling in Cholangiocarcinoma

Researcher: Saireudee Chaturantabut PhD, Broad Institute of MIT & Harvard

Amount: $50,000

"FGFR2 gene mutations occur frequently in cholangiocarcinoma (CCA) causing overactivation of a critical growth promoting pathway. This finding has led to the successful testing of new drugs targeting FGFR in preclinical and clinical trials. Nevertheless, studies have found drug resistance and adverse effects in patients treated with FGFR inhibitors suggesting that drug inhibitors alone may not be sufficient to cure CCA patients. A better understanding of FGFR2 in CCA biology and alternative therapeutic approaches are therefore critical and are the focus of this proposal. Here, we propose to explore antibody-based treatment strategies that we believe will lead to higher efficacy and lower toxicity, and the ability to overcome resistance. We will test these antibodies in CCA cell lines as well as in CCA animal models. We will further utilize novel technologies to engineer and improve current antibodies such that they may have enhanced therapeutic impact in ICC patients."

2019 Jacques Dupont Award

Supported by Barbara Dupont, family & friends in memory of Jacques Dupont

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B7-H3 specific CAR T Cell Combinatorial Immunotherapy for ICC

Researcher: Theodorous Michelakos MD, MGH

Amount: $50,000

"The lack of curative therapies for intrahepatic cholangiocarcinoma has prompted us to develop a novel and highly effective immunotherapeutic strategy. We target the tumor-specific antigen B7-H3 using genetically engineered T lymphocytes (CAR T cells). To enhance the efficacy of this strategy we utilize techniques to counteract the escape mechanisms used by tumor cells to evade destruction by the immune system. Our study is expected to generate clinically relevant results that will contribute to the design of CAR T cell-based clinical trials for patients with cholangiocarcinoma."

2019 Margaret M. Brown Award

Supported by Janice (current patient) and Dean Meyer – in honor of her mother who also died from CCA.

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Understanding DKK1/GRP78 interactions and the implications for the tumour microenvironment in cholangiocarcinoma

Researcher: Edward Jarman PhD, University of Edinburgh

Amount: $50,000

“DKK1 overexpression has been associated with poor prognosis and more aggressive disease in CCA.  However, the mechanism of action is still poorly understood. We propose that DKK1 may facilitate tumour progression through modulation of immune cells in the tumour microenvironment. This study will
investigate the interaction between DKK1 and GRP78 to understand whether DKK1 can co-opt GRP78 into modifying immune cell behaviour and promote a permissive immune environment for tumour growth.”

2019 Marion U. Schwartz Award

Supported by CCF in memory of Marion U. Schwartz

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Gut microbiome-dependent accumulation of myeloid cells promotes intrahepatic cholangiocarcinoma

Researcher: Qianfei Zhang MD, NCI/NIH

Amount: $50,000

"Intrahepatic cholangiocarcinoma (ICC) is a rare but very aggressive malignancy with no effective treatment options. Gaining insight into the pathologic mechanisms of ICC is crucial to developing novel therapies. Livers of patients with ICC have increased myeloid cells, which can suppress the immune system and promote cancer. Little is known about why these cells accumulate into liver. Various disease states can cause gut microbiome translocated into liver, where bacteria interact with liver cells resulting in production of substances that can potentially recruit myeloid cells to the liver. The relationship between increased bacteria and accumulated myeloid cells in the liver has not been carefully examined. We hypothesize that presence of gut microbiome in the liver and the subsequent increase in myeloid cells contribute to promoting ICC."

2019 Mark R. Clements Award

Supported by Brad & Geri Clements in memory of Mark R. Clements

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Investigating YAP inhibition as a novel treatment for Intrahepatic cholangiocarcinoma

Researcher: Jacquelyn Russell PhD, Boston Children’s Hospital

Amount: $50,000

"Our grant aims to determine the role of YAP in cholangiocarcinoma, as it is a protein found to be abnormally activated in a large majority of cholangiocarcinoma cases. We predict inhibition of YAP signaling may be a viable treatment strategy for cholangiocarcinoma, and to this end we have developed a mouse model of cholangiocarcinoma and novel YAP inhibitors. We hope these experiments will provide the foundation for a new therapeutic strategies for the treatment of this deadly liver cancer."

2019 Collaboration Award

Supported by Lorraine Twohill in honor of the collaboration between CCF, Target Cancer, AMMF & BiliProject

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Deciphering the role of the IDH mutant in the tumor immune microenvironment of cholangiocarcinoma

Researcher: Meng-Ju Wu PhD, MGH

Amount: $65,000

"IDH 1 mutation (IDHm) are common in ICC. While IDHm inhibitors show benefit in clinical trials, efficacy is not durable. It is critical to decipher the impact of IDH inhibition on ICC tumor and stromal cells and to use this information to identify synergistic or alternative therapeutic approaches. My project is to test the hypothesis that IDHm-driven metabolic reprogramming alters tumor-immune communication, and identify approaches to both more effectively target tumor cells and restore anti-tumor immunity."

2018 Research Fellowship Awards

2018 Tommy J. West Memorial Research Fellowship

Role of PlGF/Nrp1 Pathway in Intrahepatic Cholangiocarcinoma Cell Survival, Tumor-associated Fibrosis and Abnormal Vasculature

Amount: $50,000

Researcher: Shuichi Aoki, MD, PhD – Harvard University

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Shuichi Aoki, MD, PhD

Harvard University

“PlGF/Nrp1 pathway is often activated in intrahepatic cholangiocarcinomas and is a potential mediator of the progression of these tumors. PlGF/Nrp1 promotes abundant extracellular matrix deposition (desmoplasia)—produced by CAFs—and formation of an abnormal vasculature in cholangiocarcinoma. We propose that anti-PlGF therapy could improve the delivery of chemotherapeutic agents and enhance the tumor immunity by reprogramming these microenvironmental abnormalities, and could also impact the clinical development of immune-checkpoint blockade in this intractable disease.”

2018 Andrea Marie Fuquay Memorial Research Fellowship

Developing Organotypic Slice Cultures as a New Model System in Cholangiocarcinoma

Researcher: Iris Sze Ue Luk, PhD – Fred Hutchinson Cancer Research Center

Amount: $50,000

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Iris Sze Ue Luk, PhD

Fred Hutchinson Cancer Research Center

"We propose to use ’tumor slice cultures’ (TSCs) to evaluate the effects of new targeted therapies for the subset of cholangiocarcinomas with mutations in a gene called isocitrate dehydrogenase 1. Ultimately, the goal of this proposal is to establish TSCs as a new experimental system which can be used cancer centers world-wide to rapidly determine drug sensitivity of tumors from patients with cholangiocarcinoma."

2018 Andrea Scott Memorial Research Fellowship

Developing FGFR2 Degrader with PROTAC Technology to Target Intrahepatic Cholangiocarcinoma

Researcher: Tinghu Zhang, PhD – Dana-Farber Cancer Institute

Amount: $50,000

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Tinghu Zhang, PhD

Dana-Farber Cancer Institute

"The altered activation of Fibroblast Growth Factor Receptor 2 (FGFR2) has been found in many ICC patients. A selective FGFR2 inhibitor has not been discovered and non-specific FGFR2 inhibitors have shown toxicities mainly due to FGFR1 inhibition in clinical trials. We will explore the PROTAC (Proteolysis targeting chimera) technology with a pan-FGFR inhibitor to develop a selective FGFR2 degrader. Our study will have great potential in developing a novel therapeutic strategy to improve the outcome of ICC patients."

2018 Jacques Dupont  Memorial Research Fellowship

Single-cell Immunogenomic Profiling of Neoantigen-reactive T Cells in Human Cholangiocarcinoma

Researcher: Chunhong Zheng, PhD – Providence Portland Medical Center

Amount: $50,000

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Chunhong Zheng, PhD

Providence Portland Medical Center

"Immunotherapies that harness the T-cell response against mutated neoantigens can mediate regression of cancers including cholangiocarcinoma, but there is large variability in efficacy between patients. My project is to characterize the molecular profiles of neoantigen-reactive T cells infiltrating cholangiocarcinoma using single-cell sequencing technologies, which may lead to the development of more effective T-cell based immunotherapies for patients with cholangiocarcinoma."

More Cholangiocarcinoma Foundation Grants

International Cholangiocarcinoma Research Network (ICRN) Biorepository

Term and Amount:

2018: $50,000
2017: $71,100
2016: $30,798

2014: $25,000
2013: $41,607
2012: $40,000

Researcher: Lewis Roberts, MD Mayo Clinic, Rochester, MN

Purpose: To develop a network of collaborating institutions pooling information for studies of the risks and outcomes of cholangiocarcinoma

The ICRN is a global collaboration of research groups from renowned institutions that are working in concert to improve knowledge about cholangiocarcinoma etiology, prevention, early detection, treatment and prognosis. The network is comprised of highly talented individuals from a spectrum of disciplines, perspectives, and research methods who share the passion to make significant scientific advances that improve outcomes for patients with cholangiocarcinoma.

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Dr. Lewis Roberts

Dr. Lewis Roberts

Mayo Clinic

“Families can provide very powerful information on genetic variations that confer risk for cancer and the information is usually transferable to the general population as well. If there is a way to obtain DNA from as many family members as possible, both affected and unaffected, this would substantially enhance our research efforts.”

The Cancer Genome Atlas (TCGA)

Term and Amount:
2015: $ 24,210.37

Researcher: Richard Wilson, McDonnell Genome Institute at Washington University

Aim:
The National Cancer Institute (NCI) Cancer Genome Atlas (TCGA) projects have the goal of providing comprehensive molecular analysis of different cancer types on multiple platforms. This study will fund exome sequencing of 15 cholangiocarcinoma samples which passed the DNA qualification criteria for TCGA but not the RNA qualification criteria.

Purpose:
To significantly boost ability to make clinically-relevant, analysis-based suggestions for possible personalized drug combinations

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Genome Wide Association Studies (GWAS)

A Program of the International Cholangiocarcinoma Research Network

Term and Amount:
2013-2017: $296,000

Researcher: Lewis Roberts, MD Mayo Clinic, Rochester, MN

Aim:
A genome-wide association study is an approach that involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Once new genetic associations are identified, researchers can use the information to develop better strategies to detect, treat and prevent the disease. Such studies are particularly useful in finding genetic variations that contribute to common, complex diseases, such as asthma, cancer, diabetes, heart disease and mental illnesses.

Purpose:
To accelerate research through the power of combining large amounts of data about genetic variations

Goals:

  • To advance understanding of factors that influence health and disease by helping scientists uncover associations between individuals and disorders that are passed from one generation to the next
  • To determine an individual's risk of developing a particular disorder.
  • To help prioritize genes or genomic regions for further investigation

LEARN MORE

 

Targeting BAP1 in Intrahepatic Cholangiocarcinoma

Term and Amount:
2014-2015: $50,000

Researcher:
Milind Javle, MD
MD Anderson Cancer Center

Purpose: To identify molecular subgroups of cholangiocarcinoma

Goals:

  • Estimate the frequency of BAP1 mutations in intrahepatic cholangiocarcinoma
  • Examine BAP1 and other genes in cholangiocarcinoma to link with diagnosis and patient outcomes
  • Develop a mouse model of BAP1 cholangiocarcinoma that can be used for further study
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Dr. Milind Javle

MD Anderson Cancer Center

“Our grant will explore cholangiocarcinoma cases that have BAP1 mutations with tumor spread to the bones and poor survival. We will examine the clinical course and outcome of these cases and also develop a mouse model that can be used for clinical studies of new drugs. We hope that through these experiments we get a better understanding of this group of cholangiocarcinoma patients and can identify better therapies.”

Second-Line Chemotherapy in Advanced Biliary Tract Cancers: A Retrospective, Multicenter Analysis of Outcomes

Term and Amount:
2015-2016: $ 38,825

Researchers and Collaborating Institutions:
R. Kate (Katie) Kelley, M.D. - UCSF-Helen Diller Family Comprehensive Cancer Center
Maeve Lowery, M.D. - Memorial Sloan Kettering Cancer Center
Laura Williams Goff, M.D. - Vanderbilt-Ingram Cancer Center

Goals:

  • To study outcomes for cholangiocarcinoma patients who did not respond to standard regimen of gemcitabine plus cisplatin
  • To design future chemotherapy trials for cholangiocarcinoma at multiple institutions
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Maeve Lowery, MD

Memorial Sloan Kettering Cancer Center
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Laura Williams Goff, MD

Vanderbilt-Ingram Cancer Center
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R. Kate (Katie) Kelley, MD

UCSF-Helen Diller Family Comprehensive Cancer Center

"This team and project arose from the first CCF Annual Conference in Utah in February 2014. We are extremely excited to initiate this important analysis to guide upcoming clinical trials of novel agents in cholangiocarcinoma, an enormous unmet clinical need in oncology. We all would like to express our deep appreciation to the CCF for fostering our collaboration and supporting this important work."

UCSF Hepatobiliary Tissue Bank

Term and Amount:
2012-2013: $40,000
2012: $40,000

Researcher: R. Kate (Katie) Kelley, MD University of California, San Francisco

Purpose: To support translational science in cancers of the biliary tract

Goals:

  • To create a biorepository of human tissue and blood specimens to advance understanding of this rare and under-studied disease

Young Investigator Award

The Conquer Cancer Foundation of ASCO Young Investigator Award (YIA) provides funding to promising investigators to encourage and promote quality research in clinical oncology. The purpose of this award is to fund physicians during the transition from a fellowship program to a faculty appointment. The Young Investigator Award is intended to support proposals with a clinical research focus on  cholangiocarcinoma.

Adr_sahaward: 
2012-2013: $60,000 American Society of Clinical Oncology

Researcher: 
Supriya Saha, MD, PhD Massachusetts General Hospital

We are proud to have supported the research leading to the publication of this paper. Our sincere thanks to our donors who made this ground-breaking research possible.

Aim: 
To raise awareness and trigger progress against cholangiocarcinoma, while providing critical early funding for physician-scientists at the beginning of their careers

Purpose:
To develop animal models, including gene mutations, to better understand cholangiocarcinoma in humans

Goal:

  • To publish findings to promote interest in scientific community and encourage investigators to focus their careers on bile duct cancer

 “Even though thousands of new patients are diagnosed with cholangiocarcinoma each year in the United States alone, many patients have only heard of the disease for the first time upon diagnosis.  Unfortunately, the lack of national attention and publicity that this important disease receives means that there are only very limited funding opportunities available.  The Cholangiocarcinoma Foundation is playing an absolutely critical role, not only in reversing that lack of national attention but also in funding research specifically aimed at helping patients with this diagnosis.  The Young Investigator Award that I received has been critical in making our foundational efforts possible.  With this funding, we have compiled what we believe is the largest cholangiocarcinoma cell line bank in the world and implemented a collaborative effort to generate more cell lines that have been genetically characterized.   In addition to a number of other studies, we used these funds to hire technician support which effectively doubled our research efforts and allowed us to develop and characterize a new mouse model of cholangiocarcinoma that can be used both to understand the fundamental mechanisms that cause cholangiocarcinoma but also to rapidly test novel potential therapies against this disease.   We hope that our work, funded by the Cholangiocarcinoma Foundation, will have a “multiplier effect,” encouraging other scientists to focus on biliary cancers as well as other philanthropic organizations to join the cause.   In short, I am extremely grateful to the Cholangiocarcinoma Foundation for their absolutely critical support of our work.”   Supriya Saha, MD, PhD Massachusetts General Hospital

 “I am very grateful to the Cholangiocarcinoma Foundation for supporting Dr. Supriya Saha through the Young Investigator Award.  Dr. Saha is an outstanding physician-scientist who has made a deep commitment to studying cholangiocarcinoma. He has developed an impressive series of model systems that are key to solving the biological and genetic processes that go awry during the progression of this cancer type. Dr. Saha has already made important insights into one of the major gene mutations found in cholangiocarcinoma patients.  With these insights and model systems in hand, he is poised to make the important next step of defining ways to combat this terrible disease. The support from the Cholangiocarcinoma Foundation has been vital in helping him to create this impressive program.” Dr. Nabeel Bardeesy Massachusetts General Hospital Cancer Center

 

Award: 
2011-2012: $57,500 American Society of Clinical Oncology Rocha,Flavio

Researcher:
Flavio G. Rocha, MD, FACS Virginia Mason Medical Center

Aim: 
To raise awareness and trigger progress against cholangiocarcinoma, while providing critical early funding for physician-scientists at the beginning of their careers

Purpose:

  • To identify biomarkers (CEACAM6 ) that can be used for diagnosis, prognosis and as potential targets for the development of novel therapies
  • To collect fluid from bile ducts to compare the levels of tumor markers and their association with presence and extent of cholangiocarcinoma

Goals:

  • To help place patients in the appropriate clinical trials.
  • To design better imaging tools
  • To develop new drugs to kill cancer cells

 “As a surgical oncology fellow at Memorial Sloan-Kettering, I became interested in the surgical management of cholangiocarcinoma but was discouraged by the minority of patients I could help with an operation. I realized that early detection is critical and that current diagnostic techniques were unreliable.  Therefore, I proposed to study proteins in the bile of patients with cholangiocarcinoma to identify novel tumor biomarkers.  With funding from an ASCO Young Investigator Award, I established a bile bank.   Upon moving to a faculty position at Virginia Mason, we identified a protein, CEACAM6, is secreted in significant quantities in the bile of cholangiocarcinoma patients compared to those with benign biliary disease.  It is currently being investigated as a tumor biomarker in a prospective clinical trial.  I was absolutely thrilled to develop a research idea from the laboratory to clinical application.  I am indebted to the Cholangiocarcinoma Foundation for providing me with the initial support to launch my academic career and help find better treatments for cholangiocarcinoma patients.” Flavio G. Rocha, MD, FACS Virginia Mason Medical Center

Long-term International Fellowship (LIFe)

Award: 
2011-2012: $60,000

Researcher: 
Dr. Suebpong Tanasanvimon University of Texas, MD Anderson Cancer Center

Aim: 
To determine differences in genetic profiles due to the presence of liver fluke

Purpose: 
To use microRNA expression patterns to investigate their relevance in cancer therapy and prognosis

Goals: 
To further the understanding of the etiology of cholangiocarcinoma

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