- (859) 257-5113
- 741 S Limestone, BBSRB B255, Lexington, KY 40536-0509
Shandong University, Shandong, China
Shandong University, Shandong, China
Osaka University School of Medicine, Japan
National Cardiovascular Center, Osaka, Japan.
University of Kentucky Medical School, Kentucky
The Li laboratory studies HDL and scavenger receptor BI (SR-BI). SR-BI is a receptor of HDL which plays a pivotal role in modulating HDL metabolism. While high HDL is well-recognized as a cardio-protective factor, mice deficient in SR-BI have a 2-fold increase in HDL levels but are susceptible to atherosclerosis, suggesting dysfunctional HDL in the absence of SR-BI. One of the focuses is to understand the mechanism of HDL dysfunction and its contribution to inflammatory diseases. Using SR-BI null mice, Li laboratory first reveals that SR-BI is a critical protective molecule against sepsis- a devastating disease costs 225,000 lives in US alone. Research focuses on understanding the molecular mechanisms underlying SR-BI protection against sepsis and cardiovascular disease with molecular, cellular and in vivo approaches, and translating the mechanistic study into effective therapy.
1. Li XA, Hatanaka K, Ishibashi-Ueda H, Yutani C, Yamamoto A. Characterization of serum amyloid P component from human aortic atherosclerotic lesions. Arterioscler Thromb Vasc Biol 1995; 15: 252-257.
2. Li XA*, Yutani C, Shimokado K. Serum amyloid P component associates with high density lipoprotein as well as very low density lipoprotein but not with low density lipoprotein. Biophys Biochem Res Commun. 1998; 244:249-252.
3. Li XA, Kokame K, Okubo K, Shimokado K, Tsukamoto Y, Miyata T, Katao H, Yutani C. Cloning and characterization of a novel human gene encoding for a zinc finger protein with 25 fingers. Biochim Biophys Acta. 1999; 1489:405-412.
4. Li XA, Titlow WB, Jackson BA, Giltiay N, Nikolova-Karakashian M, Uittenbogaard A, Smart EJ. High Density Lipoprotein Binding to Scavenger Receptor, Class B, Type I Activates Endothelial Nitric-oxide Synthase in a Ceramide-dependent Manner. J Biol Chem. 2002; 277: 11058-1063.
5. Dressman J, Kincer J, Matveev SV, Guo L, Greenberg R, Guerin T, Meade D, Li XA, Zhu W, Uittenbogaard A, Wilson ME, Smart EJ. HIV Protease Inhibitors Promote Atherosclerotic Lesion Formation in Mice by Increasing CD36-Dependent Cholesterol Accumulation in macrophages. J Clin Invest. 2003, 111: 385-397.
6. Gong M, Wilson M, Kelly T, Su W, Dressman J, Kincer J, Matveev SV, Guo L, Guerin T, Li XA, Zhu W, Uittenbogaard A, Smart EJ. Estradiol Associated with Female HDL Stimulates Endothelial Nitric Oxide Synthase and Vessel Relaxation in an SR-BI-Dependent Manner. J Clin Invest. 2003 111: 1579-1587
7. Li XA, Guo L, Dressman J, Asmis R, Smart EJ. A novel ligand-independent apoptotic pathway induced by scavenger receptor class B, type I and suppressed by endothelial nitric-oxide synthase and high density lipoprotein. J Biol Chem. 2005, 280:19087-96.
8. Li XA*, Guo L, Asmis R, Nikolova-Karakashian M, Smart EJ. Scavenger receptor BI Prevents Nitric Oxide-induced Cytotoxicity and Endotoxin-induced Death. Circ. Res. 2006, 98: 60-65.
9. Li J, White J, Guo L, Zhao X, Wang J, Smart EJ and Li XA*. Salt inactivates endothelial nitric oxide synthase in endothelial cells. J Nutrition 2009; 139:447-451. PMC2646221
10. Guo L, Song Z, Li M, Wu Q, Wang D, Feng H, Bernard P, Daugherty A, Bin H and Li XA*. SR-BI protects against septic death through its roles in modulating inflammatory response. J Biol Chem. 2009; 284: 19826-19834. PMC2740408
11. Feng H and Li XA*. Dysfunctional HDL. Curr Opin Endocrinol Diabetes Obese 2009; 16:156-162. PMC3065374
12. Song Z, Cai L, Guo L, Tsukamoto Y, Yutani C and Li XA*. Serum amyloid P component specifically accumulated in human atherosclerotic lesions. Atherosclerosis 2010; 211: 90-95. PMC2888759
13. Feng H, Guo L, Song Z, Wang D, Han J, Li Z, Huang H and Li XA*. Caveolin-1 prevents sepsis through its role in modulating inflammatory response, alleviating bacterial burden and suppressing thymocyte apoptosis. J Biol Chem 2010; 285: 25154-25160. PMC2919077
14. Li M, Fu W and Li XA* Differential fatty acid profile in adipose and non-adipose tissues in obese mice. Int J Clin Exp Med 2010; 3: 315-319. PMC2971542
15. Guo L, Chen M, Song Z, Daugherty A and Li XA*. C323 of SR-BI is required for SR-BI-mediated HDL binding and cholesteryl ester uptake. J Lipid Res. 2011; 52: 22272-2278. PMC3202973
16. Feng H, Guo L, Wang D, Gao H, Hou G, Zheng Z, Ai J, Forman O, Daugherty A and Li XA*. Impaired lymphocyte homeostasis and autoimmune disorder in mice deficient in HDL receptor SR-BI. Arterioscler Thromb Vasc Biol 2011; 31: 2543-2551. PMC3220294
17. Guo L, Zheng Z, Ai J, Huang H, and Li XA*. Comments on “Class B scavenger receptor types I and II and CD36 targeting improves sepsis survival and acute outcomes in mice”. J Immunol. 2012; 189:501. PMID:22773661
18. Guo L, Ai J, Zheng Z, Deborah AH, Daugherty A, Huang B and Li XA*. HDL protects against polymicrobial-induced sepsis in mice. J Biol Chem 2013; 288:17947-17953. PMC3689940
19. Xiang B, Zhang G, Guo L, Li XA, Morris A, Daugherty A, Whiteheart S, Smyth S and Zhenyu Li Z. Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 (COX1) signaling pathway. Nature Communications 2013; 4: Article number 2657.
20. Zheng Z, Ai J and Li XA*. Scavenger receptor BI and immune dysfunctions. Curr Opin Endocrinol Diabetes Obese 2014; 21: 121-128.
21. Osuchowski MF, Remick DG, Lederer JA, Lang CH, Aasen AO, Aibiki M, Azevedo LC, Bahrami S, Boros M, Cooney R, Cuzzocrea S, Jiang Y, Junger WG, Hirasawa H, Hotchkiss RS, Li XA, Radermacher P, Redl1 H, Salomao R, Soebandrio A, Thiemermann C, Vincent JL, Ward P, Yao YM, Yu HP, Zingarelli B, Chaudry IH. ABANDON THE MOUSE RESEARCH SHIP? NOT JUST YET! Shock 2014; 41: 463-475. PMC4139038 (invited review)
22. Guo L, Zheng Z, Ai J, Deborah AH, Mittelstadt PR, Thacker S, Daugherty A, Ashwell JD, Remaley A and Li XA*. Scavenger receptor BI and HDL regulate thymocyte apoptosis in sepsis. Arterioscler Thromb Vasc Biol 2014; 34: 966-975. PMC4010389
23. Guo L, Zheng Z, Ai J, Huang B and Li XA*. Hepatic scavenger receptor BI protects against polymicrobial-induced sepsis through promoting LPS clearance in mice. J Biol Chem 2014; 289: 14666-14673. PMC4031522.
24. Pollard R.D.; Blesso, C.N.; Zabalawi, M.; Fulp, B.; Gerelus, M.; Zhu, X.; Lyons, E.W.; Nuradin, N.; Francone, O.L.; Li, XA.; Sahoo, D.; Thomas, M.J.; Sorci-Thomas, M.G. Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density Lipoprotein (HDL)-Cholesteryl Ester Uptake. J Biol Chem 2015: 290: 15496-511. PMC4505464
25. Ai J, Guo L, Zheng Z, Wang SX, Huang B and Li XA*. Corticosteroid therapy benefits septic mice with adrenal insufficiency but harms septic mice without adrenal insufficiency. Critical Care Medicine 2015; 43: e490-e498.
26. Morin E, Guo L, Schwendeman A, and Li XA*. HDL in sepsis - risk factor and therapeutic approach. Front. Pharmacol. 2015; 6: 244. Doi 10.3389/fphar.2015.00244
27. Jiang K, Liu Y, Fan J, Zhang J, Li XA, Evers M, Zhu H and Jia J. PI(4)P promotes phosphorylation and conformational change of Smoothened through interaction with its C-terminal tail. PloS Biol 2016. http://dx.doi.org/10.1371/journal.pbio.1002375