Sharon DeMorrow, PhD
Professor, Associate Head
Education and Post-Graduate Training
BSc (Hon I), 1991-1994, Department of Biochemistry, University of Queensland, Brisbane, Australia
PhD, 1995-1999, Department of Biochemistry, University of Queensland, Brisbane, Australia
Postdoctoral, 2000-2003, Max Planck Institute for Psychiatry, Munich, Germany
Postdoctoral, 2003-2004, Johannes Gutenberg University, Mainz, Germany
Postdoctoral, 2005-2007, Scott & White Hospital, Temple, Texas
My research program broadly focuses on the neurological changes associated with liver disease. As a result liver dysfunction, due to either acute liver failure or chronic liver disorders, there exist alterations in brain function. These alterations range from changes in neuropeptide hormone expression, through to severe cognitive impairment and hepatic coma (termed hepatic encephalopathy). We are focused on determining the signaling molecules released from an impaired liver that may alter brain function.
Our significant contributions to the field include:
- The first demonstration that bile acid receptors and transporters are expressed in various brain regions and aberrant bile acid signaling contributes to the neurological changes associated with acute and chronic liver diseases. These observations also have implications in other neurological disorders including Alzheimer’s disease, multiple sclerosis, TBI and PTSD, all of which have recently been shown to have aberrant bile acid signaling as a component.
- Down stream of aberrant central bile acid signaling is a buildup in cholesterol in the brain during hepatic encephalopathy and strategies to inhibit cholesterol accumulation are neuroprotective (Provisional patent filed)
- During acute liver failure, TGFb is released from hepatocytes, increasing circulating levels of TGFb which in turn alter cytokine and growth factor (eg IGF1) expression in the brain, thereby contribute to the neurological decline
Together, we hypothesize that the neurological complications of liver failure can be attributed, at least in part, to the co-ordinate actions of bile acid signaling and inflammatory cytokine signaling in the brain leading to aberrant signal transduction pathways and ultimately neuronal dysfunction.
- McMillin M, Frampton G, Grant S, Khan S, Diocares J, Petrescu P, Wyatt A, Kain J, Jefferson B, DeMorrow S. Bile acid-mediated sphingosine-1-phosphate receptor 2 signaling promotes neuroinflammation during hepatic encephalopathy in mice. Front Cell Neurosci. 2017 Jul 5;11:191. doi: 10.3389/fncel.2017.00191. PMID: 28725183; PMCID: PMC5496949
- Liere V, Sandhu G, DeMorrow S. Recent advances in hepatic encephalopathy. F1000Research 2017;6(F1000 Faculty Rev):1637.
- McMillin M, Frampton G, Grant S, DeMorrow S. The Neuropeptide Galanin Is Up-Regulated during Cholestasis and Contributes to Cholangiocyte Proliferation. Am J Pathol. 2017 Apr;187(4):819-830. doi: 10.1016/j.ajpath.2016.12.015. PMID: 28196718; PMCID: PMC5397710 [Available on 2018-04-01]
- McMillin M, Grant S, Frampton G, Andry S, Brown A, DeMorrow S. Fractalkine suppression during hepatic encephalopathy promotes neuroinflammation in mice. J Neuroinflammation. 2016 Aug 26;13(1):198. doi: 10.1186/s12974-016-0674-8. PMID: 27561705; PMCID: PMC5000400
- McMillin M, DeMorrow S. Effects of bile acids on neurological function and disease. FASEB J. 2016 Nov;30(11):3658-3668. doi: 10.1096/fj.201600275R. PMID: 27468758; PMCID: PMC5067249 [Available on 2017-11-01]
- McMillin M, Frampton G, Quinn M, Ashfaq S, de los Santos M, 3rd, Grant S, DeMorrow S. Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure. Am J Pathol. 2016 Feb;186(2):312-23. doi: 10.1016/j.ajpath.2015.10.005. PMID: 26683664; PMCID: PMC4729266
- McMillin M, Frampton G, Quinn M, Divan A, Grant S, Patel N, Newell-Rogers K, DeMorrow S. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling. Mol Endocrinol. 2015 Dec;29(12):1720-30. doi: 10.1210/me.2015-1087. PMID: 26431088; PMCID: PMC4664228
- McMillin M, Frampton G, Tobin R, Dusio G, Smith J, Shin H, Newell-Rogers K, Grant S, DeMorrow S. TGR5 signaling reduces neuroinflammation during hepatic encephalopathy. J Neurochem. 2015 Nov;135(3):565-76. doi: 10.1111/jnc.13243. PMID: 26179031; PMCID: PMC5031412
- McMillin MA, Frampton GA, Seiwell AP, Patel NS, Jacobs AN, DeMorrow S. TGFb1 exacerbates blood-brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of MMP9 and downregulation of claudin-5. Lab Invest. 2015 Aug;95(8):903-13. doi: 10.1038/labinvest.2015.70. PMID: 26006017; PMCID: PMC5040071
- Quinn M, McMillin M, Galindo C, Frampton G, Pae HY, DeMorrow S. Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms. Dig Liver Dis. 2014 Jun;46(6):527-34. doi: 10.1016/j.did.2014.01. PMID: 24629820; PMCID: PMC4065628