Research Investigators - Lustgarten Foundation: Pancreatic Cancer Research

Research Investigators

Funding Breakthrough Research into Pancreatic Cancer

Andrew Feinberg, M.D., M.P.H.

Johns Hopkins University School of Medicine
Funding: $1 million over 3 years (2018-2020)
Project: Targeting the epigenomic-metabolomic foundation of PDAC metastasis

Dr. Feinberg’s team has recently identified a link between metabolism and changes in epigenetics, which is the information the cell uses to know which genes should be on and which genes should be off. They are developing new chemical inhibitors to understand the relationship between metabolism and epigenetics in metastasis, to serve as new agents to stop metastasis, and to better understand the genes that are involved in the process.

Please click here to learn more about epigenetics.

About Dr. Feinberg:
Dr. Feinberg is the director of the Center for Epigenetics, chief of the Division of Molecular Medicine in the Department of Medicine, and the King Fahd Professor of Medicine, Oncology, Molecular Biology & Genetics in the School of Medicine at Johns Hopkins University.
His research into hereditary inheritance of traits outside of DNA was initially seen as controversial, and he was told that if he continued this work, his funding would be cut off. He continued that work and in 1983 discovered epigenetic alterations in human cancer with Dr. Bert Vogelstein. He is also credited with the discovery of gene imprinting in humans. He has made many contributions to the field of epigenetics in cancer.

For more information, please click here.

A discussion with Dr. Feinberg:

LF: What is the impact of your work?
AF: Our work addresses a breakthrough in pancreatic cancer research in understanding what causes pancreatic cancer to spread. Our goal with this epigenetic research is to develop new drugs that will inhibit metastasis.

LF: Why is this funding important for your research?
AF: This funding allows us to perform exploratory research on our new findings that might have a practical application to patients. Usually, a scientist has to choose a basic research problem or drug development, but in a new area like this, the two go together.

LF: What is your message to patients?
AF: Pancreatic cancer is personal for me. My grandmother died from it and a friend was recently diagnosed with advanced disease. My team and I are working every day to make a difference for patients.

Tony Hunter, Ph.D.

Salk Institute for Biological Studies
Funding: $1 million over 3 years (2018-2020)
Project: Understanding the value of LIF (leukemia inhibitorY factor) serum level as a biomarker of pancreatic cancer

Leukemia inhibitory factor (LIF) is a protein highly expressed in pancreatic cancer that helps sustain tumor growth and blunts the body’s immune response to the tumor. Dr. Hunter’s goal is to validate LIF as a biomarker and identify how it can influence the immune system.

Please click here to learn more about epigenetics.

About Dr. Hunter:
Dr. Hunter is a Professor of Biology at the Salk Institute for Biological Studies and the University of California San Diego. He is one of the foremost leaders in the field of cell growth control, growth factor receptors and their signal transduction pathways. Dr. Hunter is known for his discovery of a mechanism called tyrosine phosphorylation, which is a molecular switch that turns normal cells cancerous. The breakthrough led to a new type of cancer pharmaceutical, the tyrosine kinase inhibitor. This class of drugs has revolutionized the treatment of chronic myeloid leukemia with the game-changing therapy Gleevec, and also is of great benefit in several other forms of cancer. Hunter’s work has led to a complete catalogue of the 90 human genes that encode tyrosine kinases, over half of which have become targets for the development of drugs to treat cancer and other human diseases. Currently, 31 tyrosine kinase inhibitors are FDA-approved for human therapy, with many more in clinical trials.

Dr. Hunter, who has many prestigious honors. is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences and the American Philosophical Society.

For more information, please click here.

Elizabeth Jaffee, M.D.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore
Funding: $1 million over 3 years (2018-2020)
Project: A Phase II study of HDAC inhibition to sensitize to immunotherapy in advanced pancreatic cancer

The immune system can unmask and destroy cancer cells. Dr. Jaffee’s lab has examined an important subset of immune cells that suppress the immune response. The drug entinostat can decrease these immunosuppressive cells and allow access to tumor-killing T-cells. This project is enrolling chemotherapy resistant pancreatic cancer patients into a Phase II clinical trial using entinostat given with the PD1-inhibitor nivolumab.

Please click here to learn more about immunotherapy.

About Dr. Jaffee:
Dr. Jaffee is an international leader in the development of immune based therapies for pancreatic and breast cancers. She is deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins; the Dana and Albert “Cubby” Broccoli professor of oncology; professor of pathology at the Johns Hopkins University School of Medicine; active staff in oncology at the Johns Hopkins Hospital; associate director for translational research, co-director of gastrointestinal cancer and diseases program, co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care; and member of the faculty, Graduate Programs in Immunology, Cellular and Molecular Medicine, and Pharmacology, at the Johns Hopkins University School of Medicine. Additionally, she is the current president of the American Association for Cancer Research (AACR) and serves on numerous other boards and committees and is one of the co-chairs of the Moonshot initiative.

Dr. Jaffee’s research is focused on the development of novel vaccine approaches that overcome immune tolerances to cancers, and she currently holds six vaccine patents.

For more information, please click here.

A discussion with Dr. Jaffee:

LF: What is the impact of your work?
EJ: Our work is trying to identify the signals in pancreatic tumor cells that inhibit the “good” killer T-cells from recognizing and eradicating the cancer. We have found a way to reprogram these signals so that the killer T-cells have full power against the cancer. Our hope is that this new approach will provide a new treatment option for patients with advanced cancer.

LF: Why is this funding important for your research?
EJ: The Lustgarten Foundation is accelerating our ability to bring new therapies discovered in our laboratories to patients quickly. The Foundation’s review and approval process is extremely thorough and efficient which enables us to achieve results much faster than other funding mechanisms.

LF: What is your message to patients?
EJ: New therapies are being discovered more quickly today due to the support of granting organizations like the Lustgarten Foundation. We want every patient to try these new therapies because they can help turn pancreatic cancer into a chronic disease rather than a lethal one.

David Pellman, M.D.

Dana-Farber Cancer Institute
Funding: $1 million over 3 years (2018-2020)
Project: Mechanisms and therapeutics for genome catastrophes that drive genome evolution in PDAC

Dr. Pellman is establishing why genome catastrophes, a phenomenon by which up to thousands of clustered chromosomal rearrangements occur in a single event, are so common in pancreatic cancer and is defining the underlying mechanisms which cause pancreatic cancer. He is also identifying potential therapies for treating pancreatic cancer based on the cellular defects that cause these genome catastrophes. Dr. Pellman and his team will primarily use pancreatic organoid cultures to model the different stages in pancreatic cancer development.

Please click here to learn more about epigenetics.

About Dr. Pellman:
Dr. Pellman is the Margaret M. Dyson Professor of Pediatric Oncology at Dana-Farber Cancer Institute, and Professor of Cell Biology at Harvard Medical School. In 2008, he was appointed as an Investigator of the Howard Hughes Medical Institute. His laboratory works to understand normal cell division mechanisms and to discover cell division defects that are unique to cancer cells. They take a range of approaches including genetics, functional genomics, biochemistry and live cell imaging.

For more information, please click here.

A discussion with Dr. Pellman:

LF: What is the impact of your work?
DP: Our work addresses the cause of pancreatic cancer. We hope that understanding the causal events will then lead to the discovery of new therapeutic strategies.

LF: Why is this funding important for your research?
DP: My laboratory has a longstanding interest in the mechanisms that drive rapid genome evolution in cancer.  It has recently been discovered by others that these events are most common in pancreatic cancer.  This funding will enable us to bring our expertise to this important clinical problem.  The Foundation has been visionary in trying to bring new thinking to the study of pancreatic cancer.

LF: What is your message to patients?
DP: There has never been a more exciting time in pancreatic cancer research where huge progress is being made based on new information about the changes to the genome.  Patients are the sole inspiration for the work we do as scientists. We are committed to building on the recent progress we have seen and want patients to have hope for better outcomes.

Hidde Ploegh, Ph.D.

Boston Children’s Hospital 
Funding: $1 million over 3 years (2018-2020)
Project: New nanobodies for use in diagnosis and therapy of pancreatic cancer

When properly stimulated, the human immune system can kill cancer cells, which makes immunotherapy a promising option in the fight against cancer, as it is already used to treat other malignancies. For an immune response against cancer to be effective, cells of the immune system known as T-cells must recognize the cancer by means of their T-cell receptors. One mechanism by which tumors resist immune attack is to deny access to such T-cells. Dr. Ploegh is working to genetically engineer T-cells with new receptors that recognize targets on newly formed blood vessels in growing pancreatic cancers. In this way it may be possible to improve access not only for T-cells, but possibly also for other biologicals that can enhance beneficial immune responses.
Additionally, the team is producing biologically active molecules that can direct T-cells toward the location of pancreatic tumors to increase their ability to kill cancer cells. Lastly, Dr. Ploegh and his team are also developing imaging to monitor the effectiveness of therapy and to do so non-invasively, an aspect often lacking in cancer trials.

Link to stimulating immune system

About Dr. Ploegh:
Dr. Ploegh is a renowned immunologist at Children’s Hospital in Boston and is known for his contributions in understanding antigen processing and the evasion of the immune system by viruses.
Much of the research by Dr. Ploegh is in the fields of biochemistry and immunology. The Ploegh lab studies molecular aspects of immune recognition, using chemical, cell biological and biochemical approaches, complemented by appropriate in vivo models. The lab is particularly interested in the use of nanobodies for non-invasive imaging by positron emission tomography (PET) scans.This has made it possible to track immune responses non-invasively, as shown for tumors in response to checkpoint blockade.

For more information, please click here.

A discussion with Dr. Ploegh:

LF: What is the impact of your work?
HP: We are among the first to develop tools that can be used to visualize what is taking place among specific sets of immune cells in the process of attacking a tumor, and to do so in a living animal. We find that at least in these preclinical mouse models, our approach has prognostic value. The utility of mouse models in developing new therapeutic strategies is exemplified by the clinical deployment of checkpoint-blocking antibodies. There is every reason to be believe that these new methods of visualizing immune responses can be used in patients as well, to better inform diagnostic and treatment options.

LF: Why is this funding important for your research?
HP: Lustgarten funding is crucial for our research, as it affords the necessary resources and flexibility to target pancreatic cancer specifically. There is a clear, practical component to what we pursue, where the underlying hypothesis is perhaps too risky to be considered for more conventional NIH-style applications. Given the current lack of options for the treatment of pancreatic cancer, we need to take a bold approach and pursue these as yet untested possibilities. The Foundation’s funding also connects us to a network of likeminded investigators, and we have already started collaborating with investigators who can provide us with materials essential for our work, such as pancreatic organoids, yet out of reach of those not specialized in this particular technology, my lab included.

LF: What is your message to patients?
HP: Basic science has come up with surprising discoveries, such as the efficacy of immunotherapy in the laboratory, which is translated soon after to the clinic. There has been an exponential increase in information on the contribution of our genes (and mutations therein) to cancer, and our understanding of our immune system continues to improve. This gives hope that there will be a time when our immune system, either on its own or with assistance from various types of drugs, can be deployed against pancreatic cancer.

Matthew Vander Heiden, M.D., Ph.D.

Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology
Funding: $1.3 million over 3 years (2017-2019)
Project: Understanding the metabolic interplay between tumor and host in pancreatic cancer

Changes in how nutrients are metabolized, or broken down for energy, contribute to both the development and progression of pancreatic cancer. However, how the cancer uses nutrients and changes a patient’s body to get the nutrients it needs, is not well understood. Dr. Vander Heiden’s previous research has shown that the breakdown of normal tissue, which is common in pancreatic cancer patients, takes place early in their disease. Dr. Vander Heiden found that breakdown of normal tissue causes levels of some amino acids in the blood to increase and that this can be one feature of early disease which may help with earlier detection.

More recently, the lab has found that a disruption of normal pancreatic function to prevent digestion of food can contribute to early tissue wasting in patients. The Vander Heiden lab has also uncovered specific ways that pancreatic cancers obtain and utilize nutrients. Dr. Vander Heiden and his team are now working to identify targets for new therapies that will stop the growth of the cancer and improve the use of existing therapies. He also aims to better understand what dietary interventions are most likely to benefit patients and to improve supportive care for patients with this devastating disease.

Please click here to learn more about tumor metabolism.

About Dr. Vander Heiden:
Dr. Vander Heiden is an associate professor in the department of biology, an associate director of the Koch Institute at MIT and a member of the Broad Institute. He is a practicing oncologist and instructor in medicine at Dana-Farber Cancer Institute/ Harvard Medical School. His work has been recognized with many awards including the Burroughs Wellcome Fund Career Award for Medical Sciences, the AACR Gertrude B. Elion Award, the HHMI Faculty Scholar Award, and the Stand Up To Cancer Phillip A. Sharp Innovation in Collaboration Award.
The focus of the Vander Heiden lab is to identify which products of metabolism create bottlenecks for cell proliferation and understand how different cancers repurpose metabolism to enable tumor growth. They are also interested in how diet and whole body metabolism influence cell metabolism in tissues to modify cancer and other disease phenotypes. Through their work, they aim to advance understanding of metabolic pathway biochemistry and its relationship to cancer.

For more information, please click here.

A discussion with Dr. Vander Heiden:

LF: What is the impact of your work?
MV: Through our work, we hope to ultimately impact the lives of patients. The past two decades of cancer research has taught us that each type of cancer is unique. We are learning that there are a variety of forces that affect the phenotype of a cancer and how it will respond to treatment. Genetic driver mutations are well-known and widely studied, but our work has reminded the field that other factors, such as tissue-of-origin and tissue context, can also play a significant role. Our work has uncovered that interactions between the tumor, whole-body metabolism and diet can affect the nutrients available to the cancer, and we aim to understand how these environmental factors impact tumor growth. These studies have had an impact on understanding how dietary factors might impact cancer outcomes, and through our work we hope to identify pancreatic cancer dependencies that can be exploited for therapeutic benefit.

LF: Why is this funding important for your research?
MV: Lustgarten Foundation funding has been transformative for my research program, and directly facilitated and empowered us to carry out collaborative and technologically advanced projects that have resulted in several high-profile papers that were published in top journals including Nature Medicine, Science, and Nature. Most importantly, the work funded by the Lustgarten Foundation has contributed new ideas to understand pancreatic cancer that we hope will directly inform future studies to help patients.

Please click here to access some of Dr. Vander Heiden’s published papers.

LF: What is your message to patients?
MV: We are all working very hard to understand the complex causes and consequences of this devastating disease. As a physician-scientist, I have seen the toll that pancreatic cancer can take on patients and their families. Knowing what they go through, drives us to work even harder to make an impact as quickly as possible. Cancer patients should keep in mind that every person and every cancer is different, so they should not be discouraged by the experiences of others. Rather, they should focus on their own journey and know that progress is being made that will one day change the reality of this cancer.

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