2022 GRANTEE: Jami Saloman, PhD
University of Pittsburgh
Research Project: Neuronal Checkpoint Signaling in Pancreas Cancer Pain
Award: 2022 Pancreatic Cancer Action Network Career Development Award in memory of Skip Viragh
Award Period: July 1, 2022 – June 30, 2024
Jami L. Saloman, PhD, is an assistant professor in the Division of Gastroenterology, Hepatology and Nutrition at the University of Pittsburgh Department of Medicine where she is a member of the Pittsburgh Center for Pain Research and the Hillman Cancer Center. Dr. Saloman received her BA from Boston University where she studied Psychology and Neuroscience. Dr. Saloman received her PhD in Neuroscience from the University of Maryland, Baltimore, where she focused on peripheral mechanisms underlying muscle pain. Dr. Saloman was a post-doctoral fellow and research faculty with Dr. Brian Davis at the University of Pittsburgh where her focus on pancreas diseases including cancer began. The focus of her research is on the role of the peripheral nervous system and neuroplasticity in multifactorial conditions (e.g., pancreas cancer and pancreatitis), that can involve both nerve injury and inflammation. She has made important contributions to tumor-associated plasticity in peripheral afferents and the role of sensory nerves in tumorigenesis. Toward this end, she utilizes a variety of approaches including in vitro and in vivo assays that assess neuro-immune interactions in the tumor microenvironment and tumor growth. She has employed novel optogenetic models and behavioral assays. Dr. Saloman has also initiated translational studies in pancreas patient populations to better understand pain in the clinical setting.
Almost all patients with pancreatic ductal adenocarcinoma, the most common type of pancreas cancer, experience pain at some point during the course of their disease. Currently, the World Health Organization advises an escalating approach to pain management in which all patients start on anti-inflammatories (e.g., NSAIDs) and escalate from weaker to strong opioids; only some patients will respond to those analgesics so a better understanding of pancreatic cancer pain is needed.
Pancreatic cancer pain can arise from several different mechanisms, including inflammation, sensitization of nerves and nerve injury. There are multiple cell types within the tumor microenvironment that interact, including the nervous and immune systems. These neuroimmune interactions can directly impact inflammation and pain signaling. Recent breakthroughs in the immunology field have led to increasing popularity in therapeutic strategies that target immune checkpoint proteins which are thought to regulate the body’s immune response to injury/pathogens. However, Dr. Saloman and her team have discovered that these proteins are also expressed on peripheral nerve fibers within pancreatic tumors.
Pancreas tumors are associated with inflammation that sensitize nerves and worsen pain. The aims of this proposal are to investigate whether the expression of checkpoint proteins in nerves modulates inflammation-mediated sensitization of nerves and pain-inducing nerve activity. The investigators will use cell culture studies to assess the role of checkpoint proteins in neuro-immune interactions as well as neuronal sensitization and signaling. They will use animal behavior assays to assess whether the presence or absence of these proteins impacts tumor-associated pain behaviors. The results of the studies will allow Dr. Saloman and her colleagues to determine whether immune checkpoint signaling is a viable analgesic target to treat pancreatic cancer pain.