On the left, Andrew Gunderson, PhD, stands with his team in his lab after securing the R01 Grant from the National Cancer Institute. On the right, Matthew Gorr, PhD, stands in his lab after securing his R01 Grand from the National Heart, Lung, and Blood Institute.  Two Department of Surgery faculty members secured R01 Grants this year. Andrew Gunderson, PhD, assistant professor in the Division of Surgical Oncology, will use a five-year, $2.5 million grant from the National Cancer Institute (NCI) to examine how clusters of immune cells function in pancreatic tumors. And Matthew Gorr, PhD, assistant professor in the Division of Cardiac Surgery, will use a five-year, $2.4 million grant from the National Heart, Lung, and Blood Institute (NHLBI) to study the biology behind pulmonary hypertension—a lung disease causing high blood pressure that can lead to the failure of the right ventricle, resulting in serious complications, including death.

NCI grant could lead to new therapies for pancreatic cancer

Dr. Gunderson is the principal investigator and says understanding how these clusters work may help scientists devise therapies to promote immune responses and improve outcomes in patients with pancreatic ductal adenocarcinoma (PDAC).

The study will further Dr. Gunderson’s work to determine why patients with PDAC typically do not respond well to immunotherapy, which is designed to boost the body’s immune response to cancer. The immune cell clusters to be studied are called tertiary lymphoid structures (TLS). In their project abstract, Dr. Gunderson and colleagues state that TLS formation in cancerous tumors is associated with improved adaptive immune function and increased survival.

The researchers hypothesize that TLS in pancreatic tumors promote the differentiation of a special kind of T cell called a “stem-like T cell” – which is a precursor to activated T cells that attack tumors – thereby enhancing T-cell responses and leading to improved tumor control. They will test their hypothesis by examining cell lines from genetically engineered mouse models and tumor samples from patients with PDAC.

This approach, they write, will help them determine how TLS supports T-cell function in mouse models of TLS+ PDAC and translate these findings to human cancer patients “so novel immunotherapy options designed to elicit and activate TLS can be offered to patients with a treatment-resistant malignancy.”

Key collaborators in this study include Zihai Li, MD, PhD; Zobeida Cruz-Monserrate, PhD; Qin Ma, PhD; Dongjun Chung, PhD; Wei Chen, MD, PhD; and Mary Dilhoff, MD. Dr. Dilhoff is principal investigator for the biobank from which PDAC patient tissue will be accessed.

NHLBI grant could advance treatments for pulmonary hypertension

Dr. Gorr — the principal investigator of the study — will analyze pulmonary hypertension using a rat model, where Dr. Gorr has found that the right ventricle has unique cellular attributes that were previously unknown.

He, along with his co-investigator Richard Gumina, MD, PhD, an associate professor with the Department of Internal Medicine, will characterize these cellular changes that occur in the right ventricle in hopes it will lead to new types of therapies for pulmonary hypertension.

His grant focuses on two types of cells that are in the heart: fibroblasts and macrophages. These cells are present in heart tissue to respond to changes occurring in heart disease, including the production of what holds cells together: extracellular matrix. What Dr. Gorr has found is that there are behaviors of both fibroblasts and macrophages particular to the right ventricle — they replicate faster and produce more extracellular matrix than the cells in the left ventricle. This may provide some explanation as to why the right ventricle has such a poor response to the changes in pressure that occur during pulmonary hypertension.

His lab will work to test these cells and see if they contain different genetic programming causing them to behave differently, and if they can alter that programming in the lab. The ultimate goal being to find new therapies to treat pulmonary hypertension.