Experimental models of immunological glomerular diseases and autoimmunity resembling those seen in man are used to obtain a fundamental understanding of the immunopathogenetic mechanisms of injury.
Antibody-mediated podocyte injury
The primary focus of the Salant laboratory is on the immune basis of glomerular diseases with particular regard to the humoral mechanisms of glomerular cell injury. Current work will elucidate the mechanisms by which antibodies alter the function and morphology of glomerular visceral epithelial cells (podocytes).
1. We have identified the target antigen in human membranous nephropathy as the phospholipase A2 receptor (PLA2R) and shown that about 75% of patients have circulating ant-PLA2R autoantibodies. Current work is directed at defining the mechanisms of podocyte injury induced by anti-PLA2R using a combination of in vitro, in vivo and human genetic techniques. Additional studies will explore the role of anti-PLA2R in the development of recurrent membranous nephropathy post renal transplantation.
2. Ongoing interests include the role of podocyte-specific antibodies, and the effects of complement-mediated injury on podocyte structure, composition of the filtration slit diaphragm and its attachment to the cytoskeleton, and on cell-matrix adhesion using animal models, cell biological and immunochemical methodologies.
Mechanisms of post-inflammatory renal fibrogenesis
We have also developed a murine model of antibody-dependent rapidly progressive glomerulonephritis in which necrotizing and crescentic glomerulonephritis is associated with the activation of chemokine and interstitial-type collagen genes, followed by the development of interstitial fibrosis and renal failure. Since interstitial fibrosis and tubular atrophy are common to all forms of chronic progressive renal diseases and are the most reliable pathological indicators of an adverse long-term prognosis in humans, this mouse model in which the onset of immune injury is rapidly followed (within 5 days) by the induction and proliferation of interstitial cells expressing high levels of mRNA for type I collagen affords a unique opportunity to study the mechanisms of post-inflammatory renal fibrogenesis
- Section Chief of Medicine in Nephrology, Nephrology, Medicine, Boston University School of Medicine
- Professor, Pathology & Laboratory Medicine, Boston University School of Medicine
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Active Staff Privileges, Nephrology, Medicine, Boston Medical Center
- University of the Witwatersrand, MBBCh
- Published on 10/26/2017
Larsen CP, Trivin-Avillach C, Coles P, Collins AB, Merchant M, Ma H, Wilkey DW, Ambruzs JM, Messias NC, Cossey LN, Rosales IA, Wooldridge T, Walker PD, Colvin RB, Klein J, Salant DJ, Beck LH. LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti-Brush Border Antibody Disease. J Am Soc Nephrol. 2017 Oct 26. PMID: 29074737.
- Published on 9/19/2017
Korte EA, Caster DJ, Barati MT, Tan M, Zheng S, Berthier CC, Brosius FC, Vieyra MB, Sheehan RM, Kosiewicz M, Wysoczynski M, Gaffney PM, Salant DJ, McLeish KR, Powell DW. ABIN1 Determines Severity of Glomerulonephritis via Activation of Intrinsic Glomerular Inflammation. Am J Pathol. 2017 Sep 19. PMID: 28935578.
- Published on 7/27/2017
Dai Y, Chen A, Liu R, Gu L, Sharma S, Cai W, Salem F, Salant DJ, Pippin JW, Shankland SJ, Moeller MJ, Ghyselinck NB, Ding X, Chuang PY, Lee K, He JC. Retinoic acid improves nephrotoxic serum-induced glomerulonephritis through activation of podocyte retinoic acid receptor a. Kidney Int. 2017 Jul 27. PMID: 28756872.
- Published on 7/15/2017
Gordon CE, Chitalia VC, Sloan JM, Salant DJ, Coleman DL, Quillen K, Ravid K, Francis JM. Thrombotic Microangiopathy: A Multidisciplinary Team Approach. Am J Kidney Dis. 2017 Nov; 70(5):715-721. PMID: 28720207.
- Published on 11/17/2016
Fan X, Yang H, Kumar S, Tumelty KE, Pisarek-Horowitz A, Rasouly HM, Sharma R, Chan S, Tyminski E, Shamashkin M, Belghasem M, Henderson JM, Coyle AJ, Salant DJ, Berasi SP, Lu W. SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and destabilizes kidney podocyte adhesion. JCI Insight. 2016 Nov 17; 1(19):e86934. PMID: 27882344.
- Published on 8/31/2016
Rasouly HM, Kumar S, Chan S, Pisarek-Horowitz A, Sharma R, Xi QJ, Nishizaki Y, Higashi Y, Salant DJ, Maas RL, Lu W. Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease. Kidney Int. 2016 Dec; 90(6):1262-1273. PMID: 27591083.
- Published on 7/19/2016
Hoxha E, Beck LH, Wiech T, Tomas NM, Probst C, Mindorf S, Meyer-Schwesinger C, Zahner G, Stahl PR, Schöpper R, Panzer U, Harendza S, Helmchen U, Salant DJ, Stahl RA. An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy. J Am Soc Nephrol. 2017 Feb; 28(2):520-531. PMID: 27436855.
- Published on 7/5/2016
Haas ME, Levenson AE, Sun X, Liao WH, Rutkowski JM, de Ferranti SD, Schumacher VA, Scherer PE, Salant DJ, Biddinger SB. The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome-Associated Hypercholesterolemia. Circulation. 2016 Jul 05; 134(1):61-72. PMID: 27358438.
- Published on 4/13/2016
Francis JM, Beck LH, Salant DJ. Membranous Nephropathy: A Journey From Bench to Bedside. Am J Kidney Dis. 2016 Jul; 68(1):138-47. PMID: 27085376.
- Published on 12/29/2015
Al-Rabadi L, Ayalon R, Bonegio RG, Ballard JE, Fujii AM, Henderson JM, Salant DJ, Beck LH. Pregnancy in a Patient With Primary Membranous Nephropathy and Circulating Anti-PLA2R Antibodies: A Case Report. Am J Kidney Dis. 2016 May; 67(5):775-8. PMID: 26744127.
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