Lu Cai, MD, PhD

Professor of Pediatrics

Director, Pediatric Research Institute

Academic Phone Number: 502-852-2669 • Email Address: lu.cai@louisville.edu

Background

Dr. Cai received his MD in 1983 and Ph.D. in 1990 from Jilin University (formally Norman Bethune University of Medical Sciences), China. He has had his postdoctoral training in the University of Western Ontario and McGill University (1993 – 1999), Canada.

Dr. Cai is tenured Professor of Departments of Pediatrics, Radiation Oncology and Pharmacology and Toxicology, and Director of Pediatric Research Institute, the University of Louisville School of Medicine.  Dr. Cai has served on the many special grant review panels and committees at the NIH, Department of Defense, American Diabetes Association, and American Heart Association.  He is author and co-author of more than 320 publications including peer-reviewed articles and/or book chapters, etc. He has been a member of the SOT since 2002 and has served the SOT in the following capacities: board councilor of regional chapter, Ohio Valley Society of Toxicology (OVSOT, 2011-2012), and special interesting group, American Association of Chinese in Toxicology (AACT, 2011-2012), and Vice-President-Elect, Vice President and President (2018 – 2021) for OVSOT. 

Research Interests:

  • Understanding the cellular and molecular mechanisms of diabetes-induced cardiovascular diseases.
  • Special interest in the role of oxidative stress, Nrf2, and antioxidants in the pathogenesis of diabetic cardiomyopathy, and radiation damage.
  • Roles of trace elements such as zinc and iron and related metallothionein in the development of diabetic complications.
  • Environmental contaminations of heavy metals such as cadmium and associate health effects.
  • Understanding the effect of low dose radiation and associated hormesis and adaptive responses.
  • Understanding the mechanisms for and possible protection from radiation-induced damage

Current Projects and Grants

  • Role of oxidative stress in diabetic complications
  • Antioxidant prevention and therapy for diabetic complication via various transgenic mouse models
  • Prevention of diabetic complications with sulforaphane, and broccoli sprout extracts via activation of Nrf2 or metallothionein
  • American Diabetes Association.  Lu Cai, MD (PI). 01/01/2018 - 12/30/2021.“Zinc-induced MT prevents diabetic cardiomyopathy by regulating CARD9/P38a MAPK”  Major Goals: This project will define the protective effect of Zninduced MT on diabetic cardiomyopathy. Role: PI
  • NIH/NHLBI, R01 HL125877.  Yi Tan, PhD (PI).   04/01/2017-03/30/22.  “A novel mechanism of stromal cell derived factor 1 protection against diabetic cardiomyopathy” Major Goals:  This project is to investigate the autophagic mechanisms responsible cadmium-induced prostate cancer.  Role: Co-PI
  • NIH/NIEHS, R01 ES030019.  Chendil Damodaran (PI).  09/01/2019-08/31/2023. “Cell survival advantage in cadmium induced carcinogenesis” Major Goals:  This project is to investigate the autophagic mechanisms responsible cadmium-induced prostate cancer.  Role: Co-PI
  • NIH/NIEHS 1R21ES033327-01.  John Wise, JR (PI).  09/01/2021 – 06/30/2023.  NIH/NIEHS 1R21ES033327-01 Cr(VI)-Induced DNA Damage Contributes to Brain Aging Role: Co-PI
  • NIH/NIDDK, 1 R01 DK132163-01.  Yi Tan, PhD (PI).  10/2021-09/2026. “Fibroblast growth factor 1 prevents hyperlipidemia and atherosclerosis”  Major Goals: This project is to define how FGF1 protects against atherosclerosis. Role: Co-PI

Selected Publications and Manuscripts in Progress

Studies related to diabetic cardiomyopathy:

  1. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence.  Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L.  Nat Rev Cardiol.2020 Aug; 22(2): 603-611PMID: 32080423
  2. Metallothionein Preserves Akt2 Activity and Cardiac Function via Inhibiting TRB3 in Diabetic Hearts. Gu J, Yan X, Dai 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.  Diabetes. 2018 Mar; 67(3): 507-517. PMID: 29079702
  3. Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy.  Gu J, Cheng Y, Wu H, Kong L, Wang S, Xu Z, Zhang Z, Tan Y, Keller BB, Zhou H, Wang Y, Xu Z, Cai L  Diabetes. 2017 Feb; 66(2): 529-542. PMID: 27903744.
  4. Inhibition of JNK phosphorylation by a novel curcumin analog prevents high glucose-induced inflammation and apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy.  Pan Y, Wang Y, Zhao Y, Peng K, Li W, Wang Y, Zhang J, Zhou S, Liu Q, Li X, Cai L, Liang G.  Diabetes. 2014 Oct; 63(10): 3497-511. PMID: 24848068.
  5. 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.  Zhao Y, Tan Y, Xi S, Li Y, Li C, Cui J, Yan X, Li X, Wang G, Li W, Cai L.  Diabetes. 2013 Jul; 62(7): 2545-58. PMID: 23423573.
  6. 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.  Tan Y, Li X, Prabhu SD, Brittian KR, Chen Q, Yin X, McClain CJ, Zhou Z, Cai L.  J Am Coll Cardiol. 2012 Apr 17; 59(16): 1477-86. PMID: 22497828
  7. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo  Tan Y, Ichikawa T, Li J, Si Q, Yang H, Chen X, Goldblatt CS, Meyer CJ, Li X, Cai L, Cui T  Diabetes. 2011 Feb; 60(2): 625-33. PMID: 21270272
  8. Inactivation of GSK-3beta by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling  Wang Y, Feng W, Xue W, Tan Y, Hein DW, Li XK, Cai L.  Diabetes. 2009 Jun; 58(6): 1391-402. PMID: 19324938
  9. Metallothionein suppresses angiotensin II-induced nicotinamide adenine dinucleotide phosphate oxidase activation, nitrosative stress, apoptosis, and pathological remodeling in the diabetic heart.  Zhou G, Li X, Hein DW, Xiang X, Marshall JP, Prabhu SD, Cai L.  J Am Coll Cardiol. 2008 Aug 19; 52(8): 655-66. PMID: 18702970
  10. Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy.  Cai L, Wang Y, Zhou G, Chen T, Song Y, Li X, Kang YJ.  J Am Coll Cardiol. 2006 Oct 17; 48(8): 1688-97. PMID: 17045908
  11. Cardiac metallothionein induction plays the major role in the prevention of diabetic cardiomyopathy by zinc supplementation.  Wang J, Song Y, Elsherif L, Song Z, Zhou G, Prabhu SD, Saari JT, Cai L.  Circulation. 2006 Jan 31; 113(4): 544-54. PMID: 16432057
  12. Inhibition of superoxide generation and associated nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy.  Cai L, Wang J, Li Y, Sun X, Wang L, Zhou Z, Kang YJ.  Diabetes. 2005 Jun; 54(6): 1829-37. PMID: 15919806
  13. Hyperglycemia-induced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway.  Cai L, Li W, Wang G, Guo L, Jiang Y, Kang YJ.  Diabetes. 2002 Jun;51(6):1938-48. PMID: 12031984

Studies related to heavy metal toxicity:

  1. Zinc as a countermeasure for cadmium toxicity. Yu HT, Zhen J, Leng JY, Cai L, Ji HL, Keller BB.  Acta Pharmacol Sin. 2021 Mar;42(3):340-346.PMID: 32284539 Review.
  2. Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals.Young JL, Yan X, Xu J, Yin X, Zhang X, Arteel GE, Barnes GN, States JC, Watson WH, Kong M, Cai L, Freedman JH. Sci Rep. 2019 Oct 11;9(1):14675. PMID: 31604971

  3. Gender Differences in Cardiac Remodeling Induced by a High-Fat Diet and Lifelong, Low-Dose Cadmium Exposure.  Liang Y, Young JL, Kong M, Tong Y, Qian Y, Freedman JH, Cai L.  Chem Res Toxicol. 2019 Jun 17;32(6):1070-1081. doi: 10.1021/acs.chemrestox.8b00386. Epub 2019 Apr 5.  PMID: 30912652

  4. Neonatal Murine Engineered Cardiac Tissue Toxicology Model: Impact of Metallothionein Overexpression on Cadmium-Induced Injury.  Yu H, Ye F, Yuan F, Cai L, Ji H, Keller BB.  Toxicol Sci. 2018 Oct 1;165(2):499-511. doi: 10.1093/toxsci/kfy177.  PMID: 29982767

  5. Inhibition of DNA methylation attenuates low-dose cadmium-induced cardiac contractile and intracellular Ca(2+) anomalies.  Turdi S, Sun W, Tan Y, Yang X, Cai L, Ren J.  Clin Exp Pharmacol Physiol. 2013 Oct;40(10):706-12. doi: 10.1111/1440-1681.12158.  PMID: 23902534

  6. The late and persistent pathogenic effects of cadmium at very low levels on the kidney of rats. Wang B, Luo Q, Shao C, Li X, Li F, Liu Y, Sun L, Li Y, Cai L. Dose Response. 2013;11(1):60-81. doi: 10.2203/dose-response.11-046.Wang. Epub 2011 Dec 2.  PMID: 23550262

  7. Transcriptional and functional studies of a Cd(II)/Pb(II)-responsive transcriptional regulator(CmtR) from Acidithiobacillus ferrooxidans ATCC 23270. Zheng C, Li Y, Nie L, Qian L, Cai L, Liu J. Curr Microbiol. 2012 Aug;65(2):117-21. doi: 10.1007/s00284-012-0117-4. Epub 2012 May 4. PMID: 22555344

  8. Low-dose Cd induces hepatic gene hypermethylation, along with the persistent reduction of cell death and increase of cell proliferation in rats and mice. Wang B, Li Y, Tan Y, Miao X, Liu XD, Shao C, Yang XH, Turdi S, Ma LJ, Ren J, Cai L. PLoS One. 2012;7(3):e33853. doi: 10.1371/journal.pone.0033853. Epub 2012 Mar 23. PMID: 22457795

  9. Proteomic characterization of the late and persistent effects of cadmium at low doses on the rat liver. Wang B, Wang S, Shao C, Wang G, Li Y, Cai L. J Appl Toxicol. 2013 Jul;33(7):546-57. doi: 10.1002/jat.1757. Epub 2011 Nov 11. PMID: 22081424

  10. Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms.  Yu HT, Zhen J, Xu JX, Cai L, Leng JY, Ji HL, Keller BB.  Acta Pharmacol Sin. 2020 May;41(5):638-649. doi: 10.1038/s41401-019-0320-y. Epub 2019 Nov 25.  PMID: 31768045

  11. Implications for prenatal cadmium exposure and adverse health outcomes in adulthood. Young JL, Cai L. Toxicol Appl Pharmacol. 2020 Sep 15;403:115161. doi: 10.1016/j.taap.2020.115161. Epub 2020 Jul 25. PMID: 32721433 Review.

  12. Effects of cadmium and high-fat diet on essential metal concentration in the mouse testis. Zhou B, Gentry A, Xu Q, Young JL, Yan X, Pagidas K, Yang Y, Watson WH, Kong M, Cai L, Freedman JH.  Toxicol Rep. 2021 Mar 20;8:718-723. doi: 10.1016/j.toxrep.2021.03.016. eCollection 2021. PMID: 33889501

  13. Zinc-metallothionein protects from DNA damage induced by radiation better than glutathione and copper- or cadmium-metallothioneins.Cai L, Cherian MG.Toxicol Lett. 2003 Jan 13;136(3):193-8. doi: 10.1016/s0378-4274(02)00359-4.PMID: 12505272

Selected Conference Publications and Presentations

2020

  1. Invited Oral permeation “Metallothionein prevents diabetic cardiomyopathy: New insight!” at the 31th Great Wall International Conference of Cardiology, digitally October 19-25, 2020;
  2. Invited Plenary Speaker “Gluco- and lipo-toxicity: Diabetic cardiomyopathy and its prevention by MT and zinc” at the Frontier Scientist Workshop 2020 and the 1st International Virtual Forum on Modern Toxicology: A 2020 Vision, December 4 and 5,2020

2019

  1. Invited oral presentation “Historical Introduction of the Research in Lu Cai’s lab in past 10 years” at the Tenth Forum of the Chinese-American Symposium of Diabetic Complications at the Ruian People’s Hospital, Ruian, Zhejiang, China, May 12, 2019.
  2. Invited oral presentation: “Zinc Homeostasis Plays Important Role in the Prevention of Obesity-induced Cardiac Hypertrophy via Regulating Innate Immune/inflammatory BCL10/CARD9/p38MAPK Pathway” at the 13th Conference of the International Society for Trace Element Research in Humans (ISTERH) in Bali, Indonesia, on September 22-26, 2019.
  3. Invited Featured Presentation "Diabetic cardiomyopathy and its prevention by metallothionein and Nrf2" at 2019 CnAHA/ACRE/CAAC Joint Research Symposium, organized by Chinese American Heart Association, Academy of Cardiovascular Research Excellence, and Chinese American Academy of Cardiology at Philadelphia, PA, on November 15, 2019.

2018

  1. Invited oral presentation “Low dose radiation and translational medicine” at the Biomedical and Environmental Session, the 17th Annual International Conference on Dose-Response: Preconditioning in Biology and Medicine- Mechanisms and Translational Research, at University of Massachusetts, Amherst, MA, April 17-18, 2018
  2. Invited oral presentation: “Potential distinct responses of normal tissue and tumors to low dose of radiation” the 3rd Global Chinese Congress of Radiation Research (GCCRR2018) in Tianjin, May 11-13, 2018
  3. Invited oral presentation “Low-dose radiation and its potential prevention of diabetic complications” for the Ninth Forum of the Chinese-American Symposium of Diabetic Complications at the Ruian People’s Hospital, Ruian, Zhejiang, China, Oct. 20, 2018.