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Xiang-An Li, PhD


741 South Limestone Street, Biomedical/Biological Sciences Research Building, Rm: B255


  • Professor
  • Regular Faculty

College Unit(s)

Other Affiliation(s)
  • CVRC - Core Faculty
  • Nutritional Sciences Graduate Faculty

Biography and Education


Shandong University, Shandong,   China




Shandong University,   Shandong, China




Osaka University School   of Medicine, Japan




National Cardiovascular Center, Osaka, Japan.



Molecular Biology

University of Kentucky Medical School, Kentucky



Molecular/Cell Biology


The Li laboratory studies HDL and HDL receptor scavenger receptor BI (SR-BI), focusing on understating the mechanisms of how the HDL/SR-BI regulates adrenal stress response, and how adrenal stress response modulates host response in sepsis and in cardiovascular disease.

Selected Publications

  1. Li XA, Hatanaka K, Guo L, Tsushima M, Kitamura Y, Yamamoto A. A sensitive peroxidase staining immunoblotting method for measuring total protein S in human plasma. Thromb Haemostas 1993; 69: 331-334.
  2. Li XA, Hatanaka K, Guo L, Kitamura Y, Yamamoto A. Binding of serum amyloid P component with heparin in human serum.  Biochim Biophys Acta 1994; 1201: 143-148.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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
  9. Li XA, Everson WV and Smart EJ. Lipid rafts, caveolae and vascular disease. Trends Cardiovasc Med. 2005, 15(3):92-6
  10. 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.
  11. Babamusta F, Rateri DL, Moorleghen JJ, Howatt DA, Li XA, Daugherty A. Angiotensin II infusion induces site-specific intra-laminar hemorrhage in macrophage colony-stimulating factor-deficient mice. Atherosclerosis 2006, 186: 282-290.
  12. Li XA, Everson W, Smart EJ. Nitric oxide, caveolae, and vascular pathology. Cardiovasc Toxicol. 2006; 6:1-14.
  13. 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.
  14. Shen H, MacDonald R, Bruemmer D, Stromberg A, Daugherty A, Li XA,  Toborek M, and Hennig B.  Zinc deficiency is detrimental to lipid metabolism in LDL-receptor-deficient mice treated with rosiglitazone. J. Nutrition 2007;137:2239-45.
  15. 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
  16. 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
  17. Feng H and Li XA*. Dysfunctional HDL. Curr Opin Endocrinol Diabetes Obese 2009; 16:156-162. PMC3065374 (invited review)
  18. Frazier WJ, Wang X, Li XA, Meng X, Nelin LD, Cato AC, Liu Y. Increased inflammation, impaired bacterial clearance, and metabolic disruption after Gram-negative bacterial infection in Mkp-1 deficient mice.  J Immunol 2009; 183: 7411 -7419. PMC2882055.
  19. Liu J, Sabeva NS, Bhatnagar S, Li XA, Pujol A, Graf GA. ABCD2 is abundant in adipose tissue and opposes the accumulation of dietary erucic acid (C22:1) in fat. J Lipid Res 2010; 51:162-168. PMC2789776
  20. 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
  21. 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
  22. 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
  23. Sabeva NS, McPhaul CM, Li XA, Cory TJ, Feola DJ and Graf G. Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells. J Nutr Biochem 2011; 22: 777-783. PMC075387
  24. Feng H, Guo L, Wang D, Gao H and Li XA*. Deficiency of calcium and magnesium induces apoptosis via scavenger receptor BI. Life Sciences 2011:88: 606-612. PMC3061308
  25. 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
  26. 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
  27. 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
  28. Cai Q, Guo L, Gao H and Li XA*. Caveolar fatty acids and acylation of caveolin-1. PLoS One 2013; 8: e60884. PMC3623963
  29. 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
  30. Feng H, Guo W, Han J and Li XA*. Role of caveolin-1 and caveolae signaling in endotoxemia and sepsis. Life Sciences 2013; 93:1-6 PMC3733535.
  31. 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.
  32. Zheng Z, Ai J and Li XA*. Scavenger receptor BI and immune dysfunctions. Curr Opin Endocrinol Diabetes Obese 2014; 21: 121-128. (invited review).
  33. 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)
  34. 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
  35. 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.
  36. 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
  37. 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.
  38. 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 PMCID: PMC4616240
  39. 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.
  40. Zheng Z, Ai J, Guo L, Ye X, Bondada S, Howatt D, Dauherty A and Li XA*. SR-BI (Scavenger Receptor Class B Type 1) is critical in maintaining normal T cell development and enhancing thymic regeneration. Arterioscler Thromb Vasc Biol. 2018; 38: 2706-2717. DOI: 10.1161/ATVBAHA.118.311728. PMC6209104.
  41. Emily E. Morin, Xiang-An Li, and Anna Schwendeman. High density lipoproteins in endocrine carcinomas: biomarker, drug carrier and potential therapeutic Front Endocrinol 2018; PMC6283888
  42. C Wu, W Lu, Y Zhang, X Zhang, G Zhang, X Shi, Y Hisashi, SP Grover, X Zhang, L Li, B Xiang, J Shi, XA Li, A Daugherty, S Smyth, D Kirchhofer, T Shiroishi, F Shao, N Mackman, Y Wei, and Z Li. Inflammasome Activation Triggers Blood Clotting and Host Death through Pyroptosis. Immunity 2019; 50: 1401. DOI: PMCID: PMC6791531
  43. Ito M, Ye X, Wang Q, Guo L, Hao D, Deborah H, Cai L, Temel R, Daugherty A, and Li XA*. Scavenger receptor BI, not LDL receptor, mediates adrenal stress response. Arterioscler Thromb Vasc Biol 2020; 40:1830-1837. PMCID: PMC7526689
  44. Wang Q, Guo L, Hao D, Ito M, Yu KJ, Wang RT, Mineo C, Shaul PW and Li XA*. Deficiency in reverse cholesterol transport in mice augments sepsis. BioRxiv 2020; doi:
  45. Misa Ito, Qian Wang, Dan Hao, Hisashi Sawada, Bin Huang, Ling Guo, Alan Daugherty and Xiang-An Li*. Ultrasound Monitoring of Thymus Involution in Septic Mice. Ultrasound in Medicine & Biology 2021; 47: 769-776. PMID: 33358338; PMCID: PMC8725176
  46. Ling Guo, Emily E. Morin, Minzhi Yu, Ling Mei, Maria V. Fawaz, Qian Wang, Yaxia Yuan, Chang-Guo Zhan, Theodore J. Standiford, Anna Schwendeman*, and Xiang-An Li* Replenishing HDL with synthetic HDL has multiple protective effects against sepsis in mice. Science Signaling. March 15, 2022; Vol. 15, Issue 725. DOI: 10.1126/scisignal.abl9322 PMC9825056
  47. Wu C-H, Guo L, Wang Q, Ye X, Mineo C, Shaul PW and Li XA*. Relative adrenal insufficiency is a risk factor and an endotype of sepsis - A proof of concept study to support a precision medicine approach for glucocorticoid sepsis therapy. Front. Immunol. 2023;13:1110516.
  48. Ling Guo, Weinan Wang, Qian Wang, Dan Hao, Misa Ito, Bin Huang, Chieko Mineo, Philip W. Shaul, Jaebok Choi, L. Frank Huang and Xiang-An Li*. Adrenal stress response is an essential host response against therapy-induced lethal immune activation. Science Signaling 2023;16:eadd4900. 10.1126/scisignal.add4900. PMCID: PMC10091512
Pubmed Publications