Dr. Maria Serena Longhi is an Assistant Professor of Anaesthesia at Harvard Medical School and holds a Visiting Senior Lecturer position with King’s College London, London, UK. She currently works as a Staff Scientist in the Department of Anesthesia, Critical Care and Pain Medicine at BIDMC. Dr. Longhi joined BIDMC in 2011 and the Department of Anesthesia, Critical Care and Pain Medicine in October 2018.

Over the years, Dr. Longhi has obtained funds from the Medical Research Council UK, King’s Health Partners UK and is currently supported by grants from the NIH and AASLD.

Dr. Longhi’s research focuses on the immune mechanisms modulating the balance between effector and regulatory cells in acute and chronic inflammatory conditions of the liver and intestine, specifically autoimmune hepatitis and inflammatory bowel disease. In previous years she has identified defects in the regulatory cell compartment in both conditions and found that these impairments are linked to dysfunction of CD39, an ectoenzyme pivotal in the maintenance of effector/regulatory cell balance in the immune system.

Dr. Longhi is currently investigating the mechanisms leading to CD39 impairment to define how this is impacted by interactions between the hydrocarbon and the oxygen related pathways. Her studies aim at dissecting: a) the role on unconjugated bilirubin, a product of heme metabolism that also activates the hydrocarbon pathway in the regulation of effector and suppressor T cell immunity in experimental colitis and human inflammatory bowel disease; b) the regulation of aryl hydrocarbon receptor signaling in human autoimmune liver diseases; and c) the transcriptional and post-transcriptional regulation of CD39 in inflammatory bowel disease.

In addition to this work, Dr. Longhi is also studying how alterations of the purinergic signaling impact predisposition to pneumonia in animal models of liver trauma and in trauma patients.

Dr. Longhi has been mentoring postgraduate research students as well as clinical and postdoctoral research fellows to aid fostering their growth as scientists and clinician scientists.

Selected Publications

Grant CR, Liberal R, Holder BS, Cardone J, Ma Y, Robson SC, Mieli-Vergani G, Vergani D, Longhi MSDysfunctional CD39(POS) regulatory T cells and aberrant control of T-helper type 17 cells in autoimmune hepatitis. Hepatology. 2014 Mar;59(3):1007-15.

Liberal R, Grant CR, Holder BS, Cardone J, Martinez-Llordella M, Ma Y, Heneghan MA, Mieli-Vergani G, Vergani D, Longhi MSIn autoimmune hepatitis type 1 or the autoimmune hepatitis-sclerosing cholangitis variant defective regulatory T-cell responsiveness to IL-2 results in low IL-10 production and impaired suppression. Hepatology. 2015 Sep;62(3):863-75.

Longhi MS, Vuerich M, Kalbasi A, Kenison JE, Yeste A, Csizmadia E, Vaughn B, Feldbrugge L, Mitsuhashi S, Wegiel B, Otterbein L, Moss A, Quintana FJ, Robson SC. Bilirubin suppresses Th17 immunity in colitis by upregulating CD39. JCI Insight. 2017 May 4;2(9).

Liberal R, Grant CR, Yuksel M, Graham J, Kalbasi A, Ma Y, Heneghan MA, Mieli-Vergani G, Vergani D, Longhi MSRegulatory T-cell conditioning endows activated effector T cells with suppressor function in autoimmune hepatitis/autoimmune sclerosing cholangitis. Liberal R, Hepatology 2017; 66(5):1570-1584. 

Xie A, Robles RJ, Mukherjee S, Zhang H, Feldbrügge L, Csizmadia E, Wu Y, Enjyoji K, Moss AC, Otterbein LE, Quintana FJ, Robson SC, Longhi MS. HIF-1a-induced xenobiotic transporters promote Th17 responses in Crohn’s disease. J Autoimmun. 2018; 94: 122-133.