Background

Dr. Tan received his PhD in Biomedical Engineering at Chongqing University, Chongqing, China in 2004. Then he became a Postdoc Fellow (2007), an Assistant Professor (2013), a tenured Associate Professor (2019), and an Endowed Chair (2020) in Departments of Pediatrics, Pharmacology and Toxicology, University of Louisville School of Medicine.

Dr. Tan has a broad background in diabetic complications and molecular pharmacology, with specific training and expertise in diabetic cardiomyopathy, vasculopathy, kidney disease, liver steatosis, and atherosclerosis. His research focuses on deciphering the mechanisms of metabolic disorder and oxidative stress in the development of diabetic complications and developing novel therapies targeting growth factors/receptors (including SDF-1, CXCR4, CXCR7, FGF1, FGF16, and FGF21) for treatment of diabetic complications, with special emphasis on developing agonists and/or antagonists targeting growth factor receptors to stimulate multiple beneficial effectors (such as MT, Nrf2, AMPK, etc.) for promoting cell redox homeostasis, metabolic programming, survival and function, and tissue repair.

Research Interests:

• The role of SDF-1/CXCR4/CXCR7 axes in diabetic complications.
• The role of FGFs (e.g.: FGF1, FGF5, FGF16, FGF21, etc.) in diabetic complications.
• Antioxidative mechanisms of metallothionein and Nrf2 in diabetic complications.

Current Projects and Grants

• Funding agency: NIH/HLBI; R01 HL160927.    

  Title: Fibroblast growth factor 1 prevents hyperlipidemia and atherosclerosis.
  Goal: The goal of this project is to define how FGF1 prevents hyperlipidemia and atherosclerosis.
  Role: PI.

• Funding agency: NIH/HLBI; R01 HL125877.    

  Title: A novel mechanism of stromal cell derived factor 1 protection against diabetic cardiomyopathy.
  Goal: The goal of this project is to define whether SDF-1 protects diabetic heart via activation of CXCR7.
  Role: PI.

• Funding agency: Kentucky Pediatric Cancer Research Trust Fund (PCRTF).

  Title: FGF1 Prevents Doxorubicin-Induced Cardiotoxicity in Pediatric Cancer Survivors.
  Goal: The goal of this project is to test the efficacy for FGF1 preventing DICM in young-tumor-bearing mice that mimic pediatric cancer survivors.
  Role: PI.

• Funding agency: NIH/NIDDK; R01 DK131442.    

  Title: The role of neutral ceramidase in intestinal fucosylation and liver steatosis and inflammation.
  Goal: The goal of this project is to define the underlying mechanisms of neutral ceramidase mediating intestinal fucosylation and liver steatosis and inflammation.
  Role: Co-I (PI: Dr. Deng, ZB).

• Funding agency: Pediatric Research Institute Start-up Fund.

  Title: The Mechanism of Diabetes-induced Endothelial Progenitor Cells Dysfunction.
  Goal: The goal of this project is to define the essential molecular mechanisms of diabetes-induced EPC dysfunction and cardiovascular disorder.
  Role: PI.

Selected Publications and Manuscripts in Progress

(selected from total 143 publications; * indicating Tan Y as corresponding or † equal contribution author)

1. Yi Tan†, Yan Li†, Jian Xiao, Hongwei Shao, Chuanlin Ding, Gavin E. Arteel, Keith A. Webster, Jun Yan, Hong Yu, Lu Cai and Xiaokun Li. A novel CXCR4 antagonist derived from human SDF-1beta enhances angiogenesis in ischaemic mice. Cardiovascular Research. 2009; 82(3):513-21. PMID: 19196827. https://pubmed.ncbi.nlm.nih.gov/19196827/
2. Tan Y†, Ichikawa T†, Li J, Si Q, Yang H, Chen X, Goldblatt CS, Meyer CJ, Li X, Cai L, Cui T. Diabetic down regulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo.Diabetes. 2011; 60(2):625-633. PMID: 21270272. https://pubmed.ncbi.nlm.nih.gov/21270272/
3. Tan Y, Li X, Prabhu SD, Brittian KR, Chen Q, Yin X, McClain CJ, Zhou Z, Cai L. Angiotensin II plays a critical role in alcohol-induced cardiac nitrative damage, cell death, remodeling, and cardiomyopathy in a protein kinase C/nicotinamide adenine dinucleotide phosphate oxidase-dependent manner.J Am Coll Cardiol. 2012; 59(16):1477-86. PMID: 22497828. https://pubmed.ncbi.nlm.nih.gov/22497828/
4. Zhao Y†, Tan Y†, Xi S, Li Y, Li C, Cui J, Yan X, Li X, Wang G, Li W, Cai L. A novel mechanism by which SDF-1β protects cardiac cells from palmitate-induced endoplasmic reticulum stress and apoptosis via CXCR7 and AMPK/p38 MAPK-mediated interleukin-6 generation. Diabetes. 2013; 62(7):2545-58. PMID: 23423573. https://pubmed.ncbi.nlm.nih.gov/23423573/
5. Zhang C, Huang Z, Gu J, Yan X, Lu X, Zhou S, Wang S, Shao M, Zhang F, Cheng P, Feng W, Tan Y*, Li X*. Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway.Diabetologia. 2015; 58(8):1937-48. PMID: 26040473. https://pubmed.ncbi.nlm.nih.gov/26040473/
6. Yan X, Chen J, Zhang C, Zeng J, Zhou S, Zhang Z, Chen J, Feng W, Li X, Tan Y*. Fibroblast growth factor 21 deletion aggravates diabetes-induced pathogenic changes in the aorta in type 1 diabetic mice.Cardiovasc Diabetol.2015, 14:77. PMID: 27391008. https://pubmed.ncbi.nlm.nih.gov/27391008/
7. Huang Z.†, Tan Y†, Gu J†, Liu Y, Song L, Niu J, Zhao L, Srinivasan L, Lin Q, Deng J, Li Y, Conklin DJ, Neubert TA, Cai L, Li X, and Mohammadi M. Uncoupling the Mitogenic and Metabolic Functions of FGF1 by Tuning FGF1-FGF Receptor Dimer Stability. Cell Rep. 2017, 20, 1717-1728. PMID: 28813681. https://pubmed.ncbi.nlm.nih.gov/28813681/
8. Dai X, Yan X, Zeng J, Chen J, Wang Y, Chen J, Li Y, Barati MT, Wintergerst KA, Pan K, Nystoriak MA, Conklin DJ, Rokosh G, Epstein PN, Li X, Tan Y*. Elevating CXCR7 improves angiogenic function of EPCs via Akt/GSK-3β/Fyn-mediated Nrf2 activation in diabetic limb ischemia.Circulation Research. 2017; 120: e7-e23. PMID: 28137917. https://pubmed.ncbi.nlm.nih.gov/28137917/
9. Gu J†, Yan X†, XDai X, Wang Y, Lin Q, Xiao J, Zhou S, Zhang J, Wang K, Zeng J, Xin Y, Barati MT, Zhang C, Bai Y, Li Y, Epstein PN, Wintergerst KA, Li X, Tan Y*, Cai L. Metallothionein preserves Akt2 activity and cardiac function via inhibiting TRB3 in diabetic hearts. Diabetes.2018; 67(3): 507-517. PMID: 29079702. https://pubmed.ncbi.nlm.nih.gov/29079702/
10. Xin Y, Bai Y, Jiang X, Zhou S, Wang Y, Wintergerst KA, Cui T, Ji H*, Tan Y*, Cai L. Prevention of Angiotensin II-induced Cardiomyopathy by Activation of Nrf2 with Sulforaphane via Stimulating the Akt/GSK-3β/Fyn Pathway. Redox Biology. 2018; 15 (2018) 405-417. PMID: 29353218. https://pubmed.ncbi.nlm.nih.gov/29353218/
11. Feifei Zhang, Zhimin Hu, Gaopeng Li, Shaofeng Huo, Fengguang Ma, Aoyuan Cui, Yaqian Xue, Yamei Han, Qi Gong, Jing Gao, Hua Bian, Zhuoxian Meng, Haifu Wu, Gang Long, Yi Tan, Yan Zhang, Xu Lin, Xin Gao, Aimin Xu, Yu Li. Hepatic CREBZF Couples Insulin to Lipogenesis by Inhibiting Insig activity and Contributes to Hepatic Steatosis in Diet-Induced Insulin-Resistant Mice. Hepatology. 2018; 68:1361-1375. https://pubmed.ncbi.nlm.nih.gov/29637572/ 
12. Wang K, Dai X, He J, Yan X, Yang C, Fan X, Sun X, Chen J, Xu J, Deng Z, Fan J, Yuan X, Liu H, Carlson EC, Shen F, Wintergerst KA, Conklin DJ, Epstein PN, Lu C, Tan Y*. Endothelial Overexpression of Metallothionein Prevents Diabetes Mellitus-Induced Impairment in Ischemia Angiogenesis via Preservation of HIF-1α/SDF-1/VEGF Signaling in Endothelial Progenitor Cells.Diabetes. 2020; 69(8): 1779-1792. PMID: 32404351. https://pubmed.ncbi.nlm.nih.gov/32404351/
13. Dai X, Yan X, Cai L, Wintergerst KA, Keller BB*, Tan Y*. Nrf2: Redox and Metabolic Regulator of Stem Cell State and Function.Trends in Molecular Medicine. 2020; 26(2): 185-200. PMID: 31679988. https://pubmed.ncbi.nlm.nih.gov/31679988/
14. Tan Y*, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L*. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence.Nature Reviews Cardiology. 2020; 17(9):585-607. PMID: 32080423. https://pubmed.ncbi.nlm.nih.gov/32080423/
15. Lin Q, Huang Z, Cai G, Fan X, Yan X, Liu Z, Zhao Z, Li J, Li J, Shi H, Kong M, Ming-Hua Zheng MH, Conklin DJ, Epstein PN, Wintergerst KA, Mohammadi M, Cai L, Li X, Li Y, Tan Y*. Activating AMPK Mediates Fibroblast Growth Factor 1 Protection from Nonalcoholic Fatty Liver Disease in Mice. Hepatology. 2021; 73(6):2206-2222. PMID: 32965675. https://pubmed.ncbi.nlm.nih.gov/32965675/
16. Rui Sun, Xuemei Gu, Chao Lei, Liang Chen, Shenghui Chu, Guangzhong Xu, Mark A Doll, Yi Tan, Wenke Feng, Leah Siskind, Craig J McClain, Zhongbin Deng. Neutral ceramidase-dependent regulation of macrophage metabolism directs intestinal immune homeostasis and controls enteric infection.Cell Rep. 2022;38(13):110560. PMID: 35354041.https://pubmed.ncbi.nlm.nih.gov/35354041/
17. Xiaozhen Dai†, Kai Wang†, Jiawei Fan†, Hanjie Liu†, Xia Fan, Qian Lin, Yuhang Chen, Hu Chen, Yao Li, Hairong Liu, Oscar Chen, Jing Chen, Xiaohong Li, Di Ren, Ji Li, Daniel J. Conklin, Kupper A. Wintergerst, Yu Li, Lu Cai, Zhongbin Deng, Xiaoqing Yan*, Yi Tan*. Nrf2 transcriptional upregulation of IDH2 to tune mitochondrial dynamics and rescue angiogenic function of diabetic EPCs.Redox Biology. 2022; 56 (2022) 102449. PMID: 36063728. https://pubmed.ncbi.nlm.nih.gov/36063728/
18. Chao Lei, Rui Sun, Guangzhong Xu, Yi Tan, Wenke Feng, Craig J. McClain, Zhongbin Deng. Enteric VIP-producing neurons maintain gut microbiota homeostasis through regulating epithelium fucosylation.Cell Host & Microbe. 2022; 30 (10): 1417–1434. PMID: 36150396. Highlighted by: Eleni Kotsiliti. Nat Rev Gastroenterol Hepatol. 2022 Oct 12. doi: 10.1038/s41575-022-00702-x. PMID: 36224272.
19. Yi Tan, Karim El-Kersh, Sarah E Watson, Kupper A Wintergerst, Jiapeng Huang, Lu Cai. Cardiovascular effects of environmental metal antimony: Redox dyshomeostasis as the key pathogenic driver.Antioxid Redox Signal. 2023 Feb 8. doi: 10.1089/ars.2022.0185. PMID: 36424825. https://pubmed.ncbi.nlm.nih.gov/36424825/