Faculty in NYU Langone’s Pancreatic Disease Laboratory work to advance current scientific understanding of the disease processes that affect the pancreas, thereby furthering the likelihood of medical prevention of these diseases. Chronic pancreatitis is a major risk factor for pancreatic carcinogenesis, but the cellular link between the two entities is to-date uncertain. Dendritic cells are central mediators of inflammation. We postulate that these dendritic cells contribute to neoplastic cancer transformation with pancreatitis. We plan to target these cells in patients and mouse models of “curable” cancer to prevent the eventual development of pancreatic cancer. Therefore, our work is specifically directed toward the following outcomes:

• determining the body’s immune response to pancreatitis, including regulatory immune cells and their response
• determining the pathogenesis behind the transformation of pancreatitis to pancreatic cancer
• developing immunologic therapies or treatments for pancreatic disease and using them as a means by which to slow or prevent the progression of pancreatitis and pancreatic cancer

Current Projects in the Pancreatic Disease Laboratory

Our lab is currently creating a pancreatitis database and investigating the biology of dendritic cells in pancreatic cancer and liver metastases in colon and pancreatic cancer.

Clinical Pancreatitis Program Database

Timely and accurate diagnosis of acute pancreatitis is of critical importance. However, available predictors of severity are based on clinical criteria alone and have proven to be poor at prognosticating which patients will progress to a severe form. We are creating the NYU Langone pancreatitis database that will include the following:

• extensive background information
• detailed, disease-specific history
• laboratory and radiographic analysis
• genetic bio-signatures
• baseline nutritional parameters
• a microbial library
• specific sensitivities to antibiotics
• short- and long-term outcomes

This extensive dataset will allow us to characterize the severity of pancreatitis in patients using established scoring systems and to correlate outcomes with biomarkers that will ultimately allow us to develop gene therapy.

Pancreatic Cancer Infiltrating Dendritic Cells

In addition to initiating immune responses against foreign invaders such as bacteria or viruses, dendritic cells also have important anti-tumor potential. This is because tumors produce proteins, or “tumor antigens,” which dendritic cells recognize as “foreign.” Dendritic cells in turn mount an immune response against the tumor cells. However, we have discovered that the dendritic cells that reside within pancreatic tumors are deficient in their ability to generate an immune response against the cancer because they are being programmatically “shut-off” by the pancreatic tumor itself. Our current research is focusing on the cellular signals that the pancreatic cancer is producing that turn off the dendritic cells from generating anti-tumor immunity.

Myeloid Suppressor Cells Promote Liver Metastases in Colon and Pancreas Cancer

The liver is the most common site of metastasis from all gastrointestinal cancers. We postulate that cancer induces immune suppression in the liver, which makes the liver fertile ground for the deposition and growth of cancerous cells that enter the blood stream. Using mouse models of both pancreatic and colon cancer, we have found that a particular cell type we call myeloid suppressor cells (MSCs) proliferate in the liver in mice with cancer. The MSCs shut off endogenous anti-tumor cells in the liver that have the potential to kill metastatic deposits. Moreover, we have shown that the MSCs cause metastatic tumors to grow faster in the liver by eliminating the anti-tumor immune response. Our current research is aimed at (1) finding an equivalent MSC in the human liver in patients with colon or pancreatic cancer and determining if these cells induce the same pro-tumor effects as we have found in rodents; and (2) targeting these cells in patients and mouse models of “curable” cancer to prevent the eventual development of liver metastases.

Our Research Team

The Department of Surgery Research Laboratory at NYU School of Medicine was founded by Dr. S. Arthur Localio in 1960. Dr. John Ranson was a pioneer in pancreatitis and pancreatic cancer research in the 1960s and 1970s. Our research team has a strong interest in determining the link between inflammation, in particular pancreatitis, and the development of pancreatic cancer as well as liver fibrosis and carcinogenesis. The ultimate goals of the laboratory are to elucidate cellular mechanisms for these diseases and work toward developing targeted therapies to halt the progression of disease.

Current Research Team Members

Dafna Bar-Sagi, PhD
Steven M. Cohen, DO
Cristina H. Hajdu, MD
Ashim Malhotra
Alec J. Megibow, MD

Support Our Research

In 2017, roughly 3 percent of the National Cancer Institute’s cancer research budget for the year was invested into pancreatic cancer research. However, the number of Americans diagnosed each year with pancreatic cancer continues to rise unlike what is seen in other leading cancers where an investment in research has led to a decrease in cancer incidences.

The lack of progress with pancreatic cancer proves that we must continue advocating for further research in the area of pancreatic disease. As physicians and medical researchers, we have committed ourselves to the fight against pancreatic disease, a battle which we would not be able to fight at all if it were not for sponsors such as you. When you choose to support us in our work you become part of our research team, and as such, we make a promise to you to keep you abreast of our successes. Therefore, you can expect to receive biannual progress reports, including copies of all publications associated with our research, ability to participate in a laboratory tour conducted yearly, and donor acknowledgement on all publications and during any institutional or national lectures.

If you are interested in donating to our pancreatic disease research, please contact Vanessa Joseph at vanessa.joseph@nyulangone.org.