Samer T. Tohme, MD
I am a Surgical Oncologist and Hepatobiliary surgeon with an interest in basic science research focusing on liver ischemia reperfusion and the effects it has on promoting metastatic tumor growth. My focus is on the liver and how stress affects the liver environment to harbor and enhance the growth of tumors. We have a large reservoir of human tissue and blood samples from patients with liver tumors.
Ongoing Research Studies:
Project: The role of neutrophil extracellular traps in promoting tumor growth.
Recent findings from our lab have revealed that cancer cells attract neutrophils and induce neutrophil extracellular traps (NET) formation in the tumor microenvironment (TME) leading to tumor growth. NETs can capture circulating cancer cells to form new metastatic foci and increase cancer cells’ invasion and migration and proliferation. Moreover, we found that in patients with primary and metastatic liver tumors, the greater the serum evidence of NET formation or the presence of NETs on biopsy/resection specimens, the higher the risk of recurrence and worse overall survival. We currently continue the effort to better understand the role of NETs in tumor growth. We are currently studying the mechanisms by which NETs can promote tumor progression by 1) interacting with the tumor microenvironment to promote an immunosuppressive protumorigenic milieu and/or 2) directly interacting with cancer cells to support metabolic adaptation through effects on cellular metabolism.
Project: The role of exercise training in sterile inflammation, liver transplant and malignancy.
Moderate exercise training is an effective pre-operative therapy that provides multiple beneficial effects on patient’s physical fitness before surgery and can improve perioperative outcomes. In our clinically relevant murine liver Ischemia reperfusion (I/R) model we have shown that exercise preconditioning mitigates the inflammatory response to liver IRI protecting the liver against sterile inflammation and injury. In addition, we have also shown that immune changes regulated by exercise training can further decrease tumor growth and metastasis to the liver. Based on our previous findings we are currently investigating the potential role of exercise as a long-term training for the innate immune response through epigenetic and metabolic changes. In addition, our lab is also investigating the role of exercise training in improving the outcomes of liver grafts subjected to cold storage during the liver transplant.
Project Title: The role of Surgery in regulating prolonged inflammatory and pro-tumorigenic immune response to facilitate tumor growth and progression
The immune system is critical in the body’s response to injury and surgical stress. Studies have shown that patients who were subjected to a variety of tissue injuries have the presence of a conserved ‘genomic storm’ that dynamically alters the leukocyte transcriptome. This results in upregulation of the innate immune response and downregulation of the adaptive immune response. These early transcriptional changes have been shown to be predictive of clinical outcomes across a range of settings. Our current study focuses on the long term effects of surgery on the inflammatory response and immune cell regulation. We are currently utilizing transcriptomic and epigenetic single cell analysis to study surgery-induced genomic alterations of the circulating and bone-marrow derived cells that precede long term pro-inflammatory and tumorigenic effects to facilitate tumor metastasis.
Division of Hepatobilliary Surgery