Xiang-An Li, Ph.D. | Saha Cardiovascular Research Center

Xiang-An Li, Ph.D.

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xli2@email.uky.edu

(859) 257-5113

741 S Limestone, BBSRB B255, Lexington, KY 40536-0509

xa Li Biosketch 2019.pdf

Position(s):

Regular Faculty

Professor

Affiliation(s):

Physiology

Cardiovascular Research Center

Other Affiliation(s):

CVRC - Core Faculty

Nutritional Sciences Graduate Faculty

Bio / Education:

Shandong University, Shandong, China	B.S.	1978-1982	Chemistry
Shandong University, Shandong, China	M.S.	1982-1985	Microbiology
Osaka University School of Medicine, Japan	Ph.D.	1991-1994	Biochemistry
National Cardiovascular Center, Osaka, Japan.	Postdoc	1998-2000	Molecular Biology
University of Kentucky Medical School, Kentucky	Postdoc	2000-2000	Molecular/Cell Biology

Research Description:

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.

Selected Publications:

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

PubMed Publications:

Wu, C.; Lu, W.; Zhang, Y.; Zhang, G.; Shi, X.; Hisada, Y ; Grover, SP ; Zhang, X.; Li, L.; Xiang, B.; Shi, J.; Li, XA ; Daugherty, A.; Smyth, SS ; Kirchhofer, D.; Shiroishi, T ; Shao, F.; Mackman, N.; Wei, Y.; Li, Z. "Inflammasome Activation Triggers Blood Clotting and Host Death through Pyroptosis." Immunity 50, 6 (2019): 1401-1411.e4. [PubMed Link] | [ Full text ]
Zheng, Z.; Ai, J.; Guo, L.; Ye, X.; Bondada, S.; Howatt, D.; Daugherty, A.; Li, XA "SR-BI (Scavenger Receptor Class B Type 1) Is Critical in Maintaining Normal T-Cell Development and Enhancing Thymic Regeneration." Arteriosclerosis, thrombosis, and vascular biology 38, 11 (2018): 2706-2717. [PubMed Link] | [ Full text ]
Morin, EE ; Li, XA ; Schwendeman, A. "HDL in Endocrine Carcinomas: Biomarker, Drug Carrier, and Potential Therapeutic." Frontiers in endocrinology 9, (2018): 715. [PubMed Link] | [ Full text ]
Yuan, B.; Wu, C.; Wang, X.; Wang, D.; Liu, H.; Guo, L.; Li, XA ; Han, J.; Feng, H. "High scavenger receptor class B type I expression is related to tumor aggressiveness and poor prognosis in breast cancer." Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37, 3 (2016): 3581-8. [PubMed Link] | [ Full text ]
Li, J.; Wang, J.; Li, M.; Yin, L.; Li, XA ; Zhang, TG "Up-regulated expression of scavenger receptor class B type 1 (SR-B1) is associated with malignant behaviors and poor prognosis of breast cancer." Pathology, research and practice 212, 6 (2016): 555-9. [PubMed Link] | [ Full text ]
Jiang, K.; Liu, Y.; Fan, J.; Zhang, J.; Li, XA ; Evers, BM ; Zhu, H.; Jia, J. "PI(4)P Promotes Phosphorylation and Conformational Change of Smoothened through Interaction with Its C-terminal Tail." PLoS biology 14, 2 (2016): e1002375. [PubMed Link] | [ Full text ]
Ai, J.; Guo, L.; Zheng, Z.; Wang, SX ; Huang, B.; Li, XA "Corticosteroid Therapy Benefits Septic Mice With Adrenal Insufficiency But Harms Septic Mice Without Adrenal Insufficiency." Critical care medicine 43, 11 (2015): e490-8. [PubMed Link] | [ Full text ]
Pollard, RD ; Blesso, CN ; Zabalawi, M.; Fulp, B.; Gerelus, M.; Zhu, X.; Lyons, EW ; Nuradin, N.; Francone, OL ; Li, XA ; Sahoo, D.; Thomas, MJ ; Sorci-Thomas, MG "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." The Journal of biological chemistry 290, 25 (2015): 15496-511. [PubMed Link] | [ Full text ]
Morin, EE ; Guo, L.; Schwendeman, A.; Li, XA "HDL in sepsis - risk factor and therapeutic approach." Frontiers in pharmacology 6, (2015): 244. [PubMed Link] | [ Full text ]
Guo, L.; Zheng, Z.; Ai, J.; Huang, B.; Li, XA "Hepatic scavenger receptor BI protects against polymicrobial-induced sepsis through promoting LPS clearance in mice." The Journal of biological chemistry 289, 21 (2014): 14666-73. [PubMed Link] | [ Full text ]
Guo, L.; Zheng, Z.; Ai, J.; Howatt, DA ; Mittelstadt, PR ; Thacker, S.; Daugherty, A.; Ashwell, JD ; Remaley, AT ; Li, XA "Scavenger receptor BI and high-density lipoprotein regulate thymocyte apoptosis in sepsis." Arteriosclerosis, thrombosis, and vascular biology 34, 5 (2014): 966-75. [PubMed Link] | [ Full text ]
Zheng, Z.; Ai, J.; Li, XA "Scavenger receptor class B type I and immune dysfunctions." Current opinion in endocrinology, diabetes, and obesity 21, 2 (2014): 121-8. [PubMed Link] | [ Full text ]
Guo, L.; Ai, J.; Zheng, Z.; Howatt, DA ; Daugherty, A.; Huang, B.; Li, XA "High density lipoprotein protects against polymicrobe-induced sepsis in mice." The Journal of biological chemistry 288, 25 (2013): 17947-53. [PubMed Link] | [ Full text ]
Feng, H.; Guo, W.; Han, J.; Li, XA "Role of caveolin-1 and caveolae signaling in endotoxemia and sepsis." Life sciences 93, 1 (2013): 1-6. [PubMed Link] | [ Full text ]
Xiang, B.; Zhang, G.; Guo, L.; Li, XA ; Morris, AJ ; Daugherty, A.; Whiteheart, SW ; Smyth, SS ; Li, Z. "Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway." Nature communications 4, (2013): 2657. [PubMed Link] | [ Full text ]
Cai, Q.; Guo, L.; Gao, H.; Li, XA "Caveolar fatty acids and acylation of caveolin-1." PloS one 8, 4 (2013): e60884. [PubMed Link] | [ Full text ]
Feng, H.; Guo, L.; Wang, D.; Gao, H.; Hou, G.; Zheng, Z.; Ai, J.; Foreman, O.; Daugherty, A.; Li, XA "Deficiency of scavenger receptor BI leads to impaired lymphocyte homeostasis and autoimmune disorders in mice." Arteriosclerosis, thrombosis, and vascular biology 31, 11 (2011): 2543-51. [PubMed Link] | [ Full text ]
Feng, H.; Guo, L.; Gao, H.; Li, XA "Deficiency of calcium and magnesium induces apoptosis via scavenger receptor BI." Life sciences 88, 13-14 (2011): 606-12. [PubMed Link] | [ Full text ]
Guo, L.; Chen, M.; Song, Z.; Daugherty, A.; Li, XA "C323 of SR-BI is required for SR-BI-mediated HDL binding and cholesteryl ester uptake." Journal of lipid research 52, 12 (2011): 2272-8. [PubMed Link] | [ Full text ]
Li, M.; Fu, W.; Li, XA "Differential fatty acid profile in adipose and non-adipose tissues in obese mice." International journal of clinical and experimental medicine 3, 4 (2010): 303-7. [PubMed Link] |
Song, Z.; Cai, L.; Guo, L.; Tsukamoto, Y.; Yutani, C.; Li, XA "Accumulation and expression of serum amyloid P component in human atherosclerotic lesions." Atherosclerosis 211, 1 (2010): 90-5. [PubMed Link] | [ Full text ]
Feng, H.; Guo, L.; Song, Z.; Gao, H.; Wang, D.; Fu, W.; Han, J.; Li, Z.; Huang, B.; Li, XA "Caveolin-1 protects against sepsis by modulating inflammatory response, alleviating bacterial burden, and suppressing thymocyte apoptosis." The Journal of biological chemistry 285, 33 (2010): 25154-60. [PubMed Link] | [ Full text ]
Li, J.; White, J.; Guo, L.; Zhao, X.; Wang, J.; Smart, EJ ; Li, XA "Salt inactivates endothelial nitric oxide synthase in endothelial cells." The Journal of nutrition 139, 3 (2009): 447-51. [PubMed Link] | [ Full text ]
Guo, L.; Song, Z.; Li, M.; Wu, Q.; Wang, D.; Feng, H.; Bernard, P.; Daugherty, A.; Huang, B.; Li, XA "Scavenger Receptor BI Protects against Septic Death through Its Role in Modulating Inflammatory Response." The Journal of biological chemistry 284, 30 (2009): 19826-34. [PubMed Link] | [ Full text ]
Feng, H.; Li, XA "Dysfunctional high-density lipoprotein." Current opinion in endocrinology, diabetes, and obesity 16, 2 (2009): 156-62. [PubMed Link] | [ Full text ]
White, J.; Guerin, T.; Swanson, H.; Post, S.; Zhu, H.; Gong, M.; Liu, J.; Everson, WV ; Li, XA ; Graf, GA ; Ballard, HO ; Ross, SA ; Smart, EJ "Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin." American journal of physiology. Cell physiology 294, 1 (2008): C295-305. [PubMed Link] | [ Full text ]
Shen, H.; MacDonald, R.; Bruemmer, D.; Stromberg, A.; Daugherty, A.; Li, XA ; Toborek, M.; Hennig, B. "Zinc deficiency alters lipid metabolism in LDL receptor deficient mice treated with rosiglitazone." The Journal of nutrition 137, 11 (2007): 2339-45. [PubMed Link] | [ Full text ]
Smart, EJ ; Li, XA "Hyperglycemia: cell death in a cave." Biochimica et biophysica acta 1772, 5 (2007): 524-6. [PubMed Link] | [ Full text ]
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 186, 2 (2006): 282-90. [PubMed Link] | [ Full text ]
Bradshaw, EL ; Li, XA ; Guerin, T.; Everson, WV ; Wilson, ME ; Bruce-Keller, AJ ; Greenberg, RN ; Guo, L.; Ross, SA ; Smart, EJ "Nucleoside reverse transcriptase inhibitors prevent HIV protease inhibitor-induced atherosclerosis by ubiquitination and degradation of protein kinase C." American journal of physiology. Cell physiology 291, 6 (2006): C1271-8. [PubMed Link] | [ Full text ]
Li, XA ; Guo, L.; Asmis, R.; Nikolova-Karakashian, M.; Smart, EJ "Scavenger receptor BI prevents nitric oxide-induced cytotoxicity and endotoxin-induced death." Circulation research 98, 7 (2006): e60-5. [PubMed Link] | [ Full text ]
Li, XA ; Everson, W.; Smart, EJ "Nitric oxide, caveolae, and vascular pathology." Cardiovascular toxicology 6, 1 (2006): 1-13. [PubMed Link] | [ Full text ]
Li, XA ; Guo, L.; Dressman, JL ; 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." The Journal of biological chemistry 280, 19 (2005): 19087-96. [PubMed Link] | [ Full text ]
Li, XA ; Everson, WV ; Smart, EJ "Caveolae, lipid rafts, and vascular disease." Trends in cardiovascular medicine 15, 3 (2005): 92-6. [PubMed Link] | [ Full text ]
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 "HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner." The Journal of clinical investigation 111, 10 (2003): 1579-87. [PubMed Link] | [ Full text ]
Dressman, J.; Kincer, J.; Matveev, SV ; Guo, L.; Greenberg, RN ; Guerin, T.; Meade, D.; Li, XA ; Zhu, W.; Uittenbogaard, A.; Wilson, ME ; Smart, EJ "HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages." The Journal of clinical investigation 111, 3 (2003): 389-97. [PubMed Link] | [ Full text ]
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." The Journal of biological chemistry 277, 13 (2002): 11058-63. [PubMed Link] | [ Full text ]