Joseph I. Shapiro, MD, FAHA, FACP, FASN

Shapiro_facultysize
Dean, Joan C. Edwards School of Medicine
Department: Internal Medicine
Office: Marshall University Medical Center (MUMC) 3408
Phone: (304) 691-1700 | Fax: (304) 691-1726
E-mail: shapiroj@marshall.edu

Research Interests

My research has focused on the mechanisms by which renal disease progresses and causes cardiovascular (CV) disease. During these investigations, I have, through my collaborations with Drs. Zijian Xie, Jiang Liu and Nader Abraham become interested in the role of Reactive Oxygen Species (ROS) in Na/K-ATPase signaling and the potential for this signaling process to serve as a therapeutic target in renal and CV disease. Our group has a number of publications related to renal sodium handling, hypertension and experimental uremic cardiomyopathy.

Shapiro_Slide57_April 2016Shapiro_Slide32_April 2016

 

 

 

 

 

 

Our group has formulated the schema below for how this signaling is involved in fibrosis as well as how it is integrated into renal proximal tubular sodium handling. These schema are shown above.

We have expanded our understanding to see the Na/K-ATPase as an intracellular amplifier for oxidant signaling.  Recently, we observed that a peptide developed to block this amplification which does not affect Na/K-ATPase ion transport is effective in ameliorating oxidant stress and attenuating adipogenesis.  This work was published in the Oct 16, 2015 issue of Science Advances.

Shapiro_Slide4_April 2016Shapiro_Slide3_April 2016

Effect of increasing pNaKtide concentrations on adipogenesis in mouse preadipocytes.

Adipogenesis was measured as the relative absorbance of Oil Red O at day 7 after inducing adipogenesis as described in Materials and Methods. (A) Representative images. (B) Quantitative data expressed as means ± SE, n = 7; *P < 0.05 versus control.

 

 

 

Effect of increasing doses of pNaKtide on metabolic profile in mice fed a high-fat diet. (A) HOMA-IR. (B) Glucose tolerance test. (C) Thiobarbituric acid–reactive substance (TBARS), a marker of oxidative injury, was measured in visceral adipose tissue. (D) Plasma adiponectin levels. Results are means ± SE, n = 7 to 14 per group; *P < 0.05 versus control, #P < 0.05 versus high-fat diet. (E to G) Effect of pNaKtide on protein carbonylation and phosphorylation of c-Src and ERK1/2 in fat tissue in mice fed a high-fat diet. (E) Protein carbonylation. (F) Phosphorylation of c-Src. (G) Phosphorylation of ERK1/2. Results are means ± SE, n = 4 to 7 per group; **P < 0.01 versus control, #P < 0.01 versus high-fat diet.

Clinical Interests

Acid-Base and Electrolyte Disturbances
Cellular Energy Metabolism
Mechanisms of Acute and Chronic Renal Failure
Renal Transplantation

Awards

American Physiological Society Cardiovascular Fellow (2013-present)
Phi Kappa Phi Honor Society (2013-present)
Castle Connolly Top Doctors (2012-present)
America’s Best Doctors (2009-present)
America’s Top Doctors (2009-present)
St. Vincent- University of Toledo Internal Medicine Excellence in Education Award (2009)

Selected Publications 

For a full listing of publications, please access PubMed.

The physiological and clinical importance of sodium potassium ATPase in cardiovascular diseases. Yan Y, Shapiro JI. Curr Opin Pharmacol. 2016 Apr;27:43-9. doi: 10.1016/j.coph.2016.01.009. Epub 2016 Feb 15. Review. PMID: 26891193

Na/K-ATPase signaling regulates collagen synthesis through microRNA-29b-3p in cardiac fibroblasts. Drummond CA, Hill MC, Shi H, Fan X, Xie JX, Haller ST, Kennedy DJ, Liu J, Garrett MR, Xie Z, Cooper CJ, Shapiro JI, Tian J. Physiol Genomics. 2016 Mar;48(3):220-9. doi: 10.1152/physiolgenomics.00116.2015. Epub 2015 Dec 23.PMID: 26702050

Role of Serum Biomarkers in Early Detection of Diabetic Cardiomyopathy in the West Virginian Population. Shaver A, Nichols A, Thompson E, Mallick A, Payne K, Jones C, Manne ND, Sundaram S, Shapiro JI, Sodhi K. Int J Med Sci. 2016 Feb 5;13(3):161-8. doi: 10.7150/ijms.14141. eCollection 2016. PMID: 26941576

Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population. Srikanthan K, Feyh A, Visweshwar H, Shapiro JI, Sodhi K. Int J Med Sci. 2016 Jan 1;13(1):25-38. doi: 10.7150/ijms.13800. eCollection 2016. Review. PMID:26816492

Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity. Sodhi K, Hilgefort J, Banks G, Gilliam C, Stevens S, Ansinelli HA, Getty M, Abraham NG, Shapiro JI, Khitan Z. Stem Cells Int. 2016;2016:8197325. doi: 10.1155/2016/8197325. Epub 2015 Nov 22. PMID:26681956

Renal Artery Stent Outcomes: Effect of Baseline Blood Pressure, Stenosis Severity, and Translesion Pressure Gradient. Murphy TP, Cooper CJ, Matsumoto AH, Cutlip DE, Pencina KM, Jamerson K, Tuttle KR, Shapiro JI, D’Agostino R, Massaro J, Henrich W, Dworkin LD.J Am Coll Cardiol. 2015 Dec 8;66(22):2487-94. doi: 10.1016/j.jacc.2015.09.073. PMID:26653621

pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis. Sodhi K, Maxwell K, Yan Y, Liu J, Chaudhry MA, Getty M, Xie Z, Abraham NG, Shapiro JI. Sci Adv. 2015 Oct 16;1(9):e1500781. doi: 10.1126/sciadv.1500781. eCollection 2015 Oct. PMID: 26601314

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet. Sodhi K, Puri N, Favero G, Stevens S, Meadows C, Abraham NG, Rezzani R, Ansinelli H, Lebovics E, Shapiro JI. PLoS One. 2015 Jun 22;10(6):e0128648. doi: 10.1371/journal.pone.0128648. eCollection 2015. PMID:26098879

Agonists of epoxyeicosatrienoic acids reduce infarct size and ameliorate cardiac dysfunction via activation of HO-1 and Wnt1 canonical pathway. Cao J, Tsenovoy PL, Thompson EA, Falck JR, Touchon R, Sodhi K, Rezzani R, Shapiro JI, Abraham NG. Prostaglandins Other Lipid Mediat. 2015 Jan-Mar;116-117:76-86. doi: 10.1016/j.prostaglandins.2015.01.002. Epub 2015 Feb 9. PMID: 25677507

Renal denervation to treat cardiac fibrosis? Wehner P, Shapiro JI. J Am Heart Assoc. 2014 Dec;3(6):e001556. doi: 10.1161/JAHA.114.001556. No abstract available. PMID: 25516440

Management of severe hyponatremia: infusion of hypertonic saline and desmopressin or infusion of vasopressin inhibitors? Tzamaloukas AH, Shapiro JI, Raj DS, Murata GH, Glew RH, Malhotra D. Am J Med Sci. 2014 Nov;348(5):432-9. doi: 10.1097/MAJ.0000000000000331. Review. PMID: 25247759

Reduction of Na/K-ATPase affects cardiac remodeling and increases c-kit cell abundance in partial nephrectomized mice. Drummond CA, Sayed M, Evans KL, Shi H, Wang X, Haller ST, Liu J, Cooper CJ, Xie Z, Shapiro JI, Tian J. Am J Physiol Heart Circ Physiol. 2014 Jun 15;306(12):H1631-43. doi: 10.1152/ajpheart.00102.2014. Epub 2014 Apr 18. PMID:24748592

Body sodium, potassium and water in peritoneal dialysis-associated hyponatremia. Sun Y, Mills D, Ing TS, Shapiro JI, Tzamaloukas AH. Perit Dial Int. 2014 May;34(3):253-9. doi: 10.3747/pdi.2012.00201. PMID:24863873

Passive immunization against marinobufagenin attenuates renal fibrosis and improves renal function in experimental renal disease. Haller ST, Drummond CA, Yan Y, Liu J, Tian J, Malhotra D, Shapiro JI. Am J Hypertens. 2014 Apr;27(4):603-9. doi: 10.1093/ajh/hpt169. Epub 2013 Sep 6. PMID:24014658

PPARδ binding to heme oxygenase 1 promoter prevents angiotensin II-induced adipocyte dysfunction in Goldblatt hypertensive rats. Sodhi K, Puri N, Kim DH, Hinds TD, Stechschulte LA, Favero G, Rodella L, Shapiro JI, Jude D, Abraham NG. Int J Obes (Lond). 2014 Mar;38(3):456-65. doi: 10.1038/ijo.2013.116. Epub 2013 Jun 19. PMID:23779049

Stenting and medical therapy for atherosclerotic renal-artery stenosis.Cooper CJ, Murphy TP, Cutlip DE, Jamerson K, Henrich W, Reid DM, Cohen DJ, Matsumoto AH, Steffes M, Jaff MR, Prince MR, Lewis EF, Tuttle KR, Shapiro JI, Rundback JH, Massaro JM, D’Agostino RB Sr, Dworkin LD; CORAL Investigators. N Engl J Med. 2014 Jan 2;370(1):13-22. doi: 10.1056/NEJMoa1310753. Epub 2013 Nov 18. PMID: 24245566

From LCME probation to compliance: the Marshall University Joan C Edwards School of Medicine experience. Miller B, Dzwonek B, McGuffin A, Shapiro JI. Adv Med Educ Pract. 2014 Oct 10;5:377-82. doi: 10.2147/AMEP.S70891. eCollection 2014. PMID:25337003

Cardiotonic steroids in adaptation to dietary salt intake. Dial L, Liu J, Shapiro JI. Curr Clin Pharmacol. 2014;9(3):298-309. Review. PMID: 24219001

The Trade-Off between Dietary Salt and Cardiovascular Disease; A Role for Na/K-ATPase Signaling? Xie JX, Shapiro AP, Shapiro JI. Front Endocrinol (Lausanne). 2014 Jul 17;5:97. doi: 10.3389/fendo.2014.00097. eCollection 2014. Review. PMID:25101054

HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets. Khitan Z, Harsh M, Sodhi K, Shapiro JI, Abraham NG. J Nutr Metab. 2014;2014:980547. doi: 10.1155/2014/980547. Epub 2014 Sep 9. PMID:25295182

Involvement of reactive oxygen species in a feed-forward mechanism of Na/K-ATPase-mediated signaling transduction. Yan Y, Shapiro AP, Haller S, Katragadda V, Liu L, Tian J, Basrur V, Malhotra D, Xie ZJ, Abraham NG, Shapiro JI, Liu J. J Biol Chem. 2013 Nov 22;288(47):34249-58. doi: 10.1074/jbc.M113.461020. Epub 2013 Oct 11. PMID:24121502

Mitochondrial impairment in the five-sixth nephrectomy model of chronic renal failure: proteomic approach. Fedorova LV, Tamirisa A, Kennedy DJ, Haller ST, Budnyy G, Shapiro JI, Malhotra D. BMC Nephrol. 2013 Oct 4;14:209. doi: 10.1186/1471-2369-14-209. PMID: 24090408

Peroxisome proliferator-activated receptor δ agonist, HPP593, prevents renal necrosis under chronic ischemia. Fedorova LV, Sodhi K, Gatto-Weis C, Puri N, Hinds TD Jr, Shapiro JI, Malhotra D. PLoS One. 2013 May 15;8(5):e64436. doi: 10.1371/journal.pone.0064436. Print 2013. PMID: 23691217

Effect of CD40 and sCD40L on renal function and survival in patients with renal artery stenosis.Haller ST, Kalra PA, Ritchie JP, Chrysochou T, Brewster P, He W, Yu H, Shapiro JI, Cooper CJ. Hypertension. 2013 Apr;61(4):894-900. doi: 10.1161/HYPERTENSIONAHA.111.00685. Epub 2013 Feb 11. PMID: 23399713

Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade. Vanella L, Sodhi K, Kim DH, Puri N, Maheshwari M, Hinds TD, Bellner L, Goldstein D, Peterson SJ, Shapiro JI, Abraham NG. Stem Cell Res Ther. 2013 Mar 12;4(2):28. doi: 10.1186/scrt176. PMID: 23497794

Gender differences in the development of uremic cardiomyopathy following partial nephrectomy: Role of progesterone. Drummond CA, Buddny G, Haller ST, Liu J, Yan Y, Xie Z, Malhotra D, Shapiro JI, Tian J. J Hypertens (Los Angel). 2013 Jan 31;2. doi: 10.4172/2167-1095.1000109. PMID: 24404431

Principles of management of severe hyponatremia. Tzamaloukas AH, Malhotra D, Rosen BH, Raj DS, Murata GH, Shapiro JI. J Am Heart Assoc. 2013 Jan 23;2(1):e005199. doi: 10.1161/JAHA.112.005199. Review. No abstract available. Erratum in: J Am Heart Assoc. 2013 Aug;2(4):e000240.  PMID: 23525443

CD36 and Na/K-ATPase-α1 form a proinflammatory signaling loop in kidney. Kennedy DJ, Chen Y, Huang W, Viterna J, Liu J, Westfall K, Tian J, Bartlett DJ, Tang WH, Xie Z, Shapiro JI, Silverstein RL. Hypertension. 2013 Jan;61(1):216-24. doi: 10.1161/HYPERTENSIONAHA.112.198770. Epub 2012 Nov 19. PMID: 23172921

Laboratory Personnel

Jiang Liu, MD, PhD – Associate Professor
Yanling Yan, PhD – Assistant Professor
Michael Dodrill, MD, PhD – Postdoctoral Fellow
Muhammad Chaudhry, MS – Research Associate
Preeya Shah, MS – Research Associate
Rebecca Martin, BS – PhD Graduate Student