Education

• Beijing University, China, Chemistry, B.Sc., 1982
• University of Leeds, England, Radiation Biochemistry, Ph.D., 1988

Honors

• Outstanding student award, Beijijng University, China, 1981.
• National Scholarship for Study in the U.K., Chinese Ministry of Education, 1984.
• Overseas Research Student Award, British Council, 1987
• Established Investigator Award, American Heart Association, 2000.
• Outstanding Oversea Scientist Award, Chinese National Science Foundation, 2002.

Research Interests:

Our research projects range from the study of the toxicity and cacinogenesis of metal ion, to the cerebral injury due to stroke, with a central focus on the role of free radicals (such as oxygen radicals, and nitric oxide) in signal transduction, and its associated oxidative damage.

Free radical injury during stroke: Stroke is the third leading cause of death in the US. Free radicals and related reactive species contribute to the cerebral damage that occurs after stroke. The overall hypothsis of our research is that free radicals generated during cerebral ischemia and reperfusion play a significant role in brain injury by either attacking tissue or by affecting gene expression of inflammatory mediators, including the cytokines and proteases. The goal of the research is to investigate the mechanism of free radical induced tissue injury, and to design better pharmacological intervention strategies to minimize the damage caused by stroke.

Metal toxicity: It is our working hypothesis that reactive metal ions (such as chromium, vanadium, and arsenic), and the free radical reactions which they mediate, play a key role in metal-induced toxicity and carcinogenicity. The goal of our research in this area is to understand the biochemical mechanisms responsible for toxicity and carcinogenesis following exposure to certain transition metal ions. Such knowledge will be useful for determining how metal toxicity can be attenuated or prevented. Toward that goal, we will attempt to answer the following questions. a) Whether free radical formation mediated by metal ions can occur under physiologically pertinent conditions. b) What is the mechanism responsible for generating the radicals. c) Whether certain metal chelators can block (or promote) the formation of the radicals. d) Whether cellular antioxidants, such as ascorbic acid and glutathione can attenuate (or exacerbate) cellular damage by these radicals. e) What is the effect of the metal ion compound and its related free radicals on gene expression. These studies should provide evidence for an oxidative damage pathway for action of metal ions on gene expression, provide insight into the mechanism by which these metal ions cause cancer, and thus provide fundamental insights into the overall mechanism of induction of the neoplastic process by carcinogens known to induce oxidative stress.

Selected Publications (from a total of over 110):

K.J. Liu, P. Gast, M. Moussavi, S.W. Norby, N. Vahidi, M. Wu and H.M. Swartz, "Lithium phthalocyanine: A probe for electron paramagnetic resonance oximetry in viable biological systems", Proc. Natl. Acad. Sci., USA, 90, 5438-5442 (1993).

K.J. Liu, M.W. Grinstaff, J. Jiang, K.S. Suslick, H.M. Swartz, and W. Wang, "In vivo measurement of oxygen concentration using sonochemically synthesized microspheres", Biophys. J., 67, 896-901 (1994).

F. Goda, J.A. O'Hara, E.S. Rhodes, K.J. Liu, G. Bacic, H.M. Swartz, "The changes of oxygen tension in experimental tumors after a single dose of X-ray radiation", Cancer Res., 55, 2249-2252 (1995).

N. Gao, M. Ding, J.Z. Zheng, Z. Zhang, S.S. Leonard, K.J. Liu, X. Shi, B.H. Jiang, "Vanadate-induced expression of hypoxia-inducible factor 1? and vascular endothelial growth factor through phosphatidylinositol 3-kinase/AKT pathway and reactive oxygen species", J. Biol. Chem., 277, 31963-31971 (2002).

S. Liu, J. Connor, S. Peterson, C.W. Shuttleworth, K.J. Liu, "Direct Visualization of trapped erythrocytes in rat brain following focal cerebral ischemia and reperfusion", J. Cereb. Blood Flow Metab., 22, 1222-1230 (2002).

S. Liu, M. Liu, S.L. Peterson, M. Miyake, V. Vallyathan, K.J. Liu, "Hydroxyl radical formation is greater in striatal core than penumbra in a rat model of ischemic stroke", J. Neurosci. Res., 71, 882-888 (2003).

A.D. Burdick, J.W. Davis II, K.J. Liu, L.G. Hudson, H. Shi, M.L. Monske, and S.W. Burchiel, "Benzo[a]pyrene quinones increase cell proliferation, generate reactive oxygen species, and thransactivate the epidermal growth factor receptor in MCF-10A cells", Cancer Res. 63, 7825-7833 (2003).

S. Liu, H. Shi, W. Liu, T. Furuichi, G.S. Timmins, K.J. Liu, "Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats", J. Cereb. Blood Flow Metab., 24, 343-349 (2004).

H. Shi, L.G. Hudson, K.J. Liu, "Oxidative stress and apoptosis in metal ion induced carcinogenesis", Free Radic Biol. Med., 37, 582-593 (2004).

S. Liu, G.S. Timmins, H. Shi, C.M. Gasparovic, K.J. Liu, "Application of in vivo EPR in brain research: monitoring tissue oxygenation, blood flow, and oxidative stress", NMR in Biomedicine, 17, 327-334 (2004).

H. Shi, L.G. Hudson, W. Ding, S. Wang, K.L. Cooper, S. Liu, X. Shi and K.J. Liu, "Arsenite causes DNA damage in keratinocytes via generation of hydroxyl radicals", Chem. Res. Tox., 17, 871-878 (2004).

Z. Liu, H. Lu, H. Shi, Y. Du, J. Yu, X. Chen, K.J. Liu, C.A. Hu, "PUMA overexpression induces reactive oxygen species generation and proteosome-mediated stathmin degradation in colorectal cancer cells", Cancer Res., 65, 1647-54 (2005).

T. Furuichi, W. Liu, H. Shi, M. Miyake, K.J. Liu, "Generation of hydrogen peroxide during brief oxygen-glucose deprivation induces preconditioning neuronal protection in primary cultured neurons", J. Neurosci. Res, 79, 816-824 (2005).

Y. Qian, K.J. Liu, D.C. Flynn, V. Castranova1, X. Shi, "Cdc42 regulates arsenic-induced NADPH oxidase activation and cell migration through actin filament reorganization", J. Biol. Chem., 280, 3875-3884 (2005).

K.J. Liu and G.A. Rosenberg, "Matrix metalloproteinases and free radicals in cerebral ischemia", Free Radic Biol. Med., 39, 71-80 (2005).

H. Shi, S. Liu, M. Miyake, K.J. Liu, "Ebselen induced C6 glioma cell death in oxygen and glucose deprivation", Chem. Res. Tox., 19, 655-660 (2006).

J. Shen, S. Ma, P. Chan, R.T.F. Cheung, P.C.W. Fung, Y. Tong, K.J. Liu, "Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury", J. Neurochem., 96, 1078-1089 (2006).

W. Liu, G.A. Rosenberg, K.J. Liu, "AUF-1 mediates inhibition by nitric oxide of LPS-induced matrix metalloproteinase-9 expression in cultured astrocytes", J. Neurosci. Res., 84, 360-369 (2006).

J. Shen, S. Liu, M. Miyake, W. Liu, A. Pritchard, J.P.Y. Kao, G.M. Rosen, Y. Tong, K.J. Liu, "Use of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an EPR oximetry probe: potential for in vivo measurement of tissue oxygenation in mouse brain", Magn. Reson. Med., 55, 1433-1440 (2006).

S. Liu, W.L. Liu, W. Ding, M. Miyake, G.A. Rosenberg, K.J. Liu, "EPR-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia", J. Cereb. Blood Flow Metab., in press.

M. Miyake, J. Shen, S. Liu, H. Shi, W. Liu, Z. Yuan, A. Pritchard, J.P.Y. Kao, K.J. Liu, G.M. Rosen, "Acetoxymethoxy ester nitroxides as EPR pro-imaging agents to measure O2 levels in mouse brain: a pharmacokinetic and pharmacodynamic study", J. Pharmacol. Exp. Therap., 318, 1187-1193 (2006).