Glomerular Disease Therapeutics Laboratory

Photo of the 3 PIs of the glomerular Disease Therapeutics Laboratory (GDTL), Drs. Sumant Chugh, Lionel Clement and Camille Mace (Camille Macé)

Glomerular Disease Therapeutics Laboratory develops novel mechanism based therapy for chronic kidney disease related to glomerular disorders, and treatment strategies for muti-system disease caused by viral cytokine storms. We use existing animal models and develop new mechanistically relevant rat models of glomerular disease to study genes and proteins that have potential in future glomerular therapeutics. We also conduct a variety of cell biology, proteomic, molecular biology and imaging studies to rigorously test our hypothesis and develop new agents for treatment of human glomerular disease. More recently, we have developed rodent models to study common cold induced relapse of primary glomerular disease, and kidney and systemic effects of the COVID-19 cytokine storm. Novel therapeutic strategies include the use of recombinant mutated human Angiopoietin-like-4 to treat chronic kidney disease, sialic acid donors for sialylation based therapeutics, depletion of specific cytokines to prevent common cold induced relapse of Minimal Change Disease and Focal and Segmental Glomerulosclerosis, targeted cytokine depletion for acute treatment of COVID-19 related multi-system injury in rodent models, and modulation of ZHX2 expression for treating systemic dysfunctions in viral cytokine storm.

In Memoriam: Caroline B. Marshall MD

GDTL News!

  1. .Eduardo Molina-Jijon PhD, postdoctoral fellow with GDTL PI Dr. Clement, featured in the Rush Mentoring Programs 2021 Reports.

Patented therapeutic strategies in accelerated development

  • The use of sialic acid based compounds in the treatment of human glomerular disease. U.S. patent has been issued, and PCT issued in some, and pending in other jurisdictions.
  • The use of recombinant human Angiopoietin-like-4 and its mutants in the treatment of Chronic Kidney Disease associated with proteinuria. Two patent families have been issued in multiple jurisdictions.
  • Targeted cytokine depletion to prevent relapse of nephrotic syndrome triggered by a common cold. PCT/US2019/042748.
  • Methods to reduce mortality caused by viral cytokine storms. US provisional patent application 63/272,402, filed 2021.
  • Methods of improving systemic disease outcomes by ZHX2 inhibition. US provisional patent application 63/272,404, filed 2021.

Selected publications

  • Molina-Jijon E, Gambut S, Macé C, Avila-Casado C, Clement LC. Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome. Kidney Int. 2020 Dec;98(6):1449-1460. PMID 32750454
  • Macé C*, Del Nogal Avila M*, Marshall CB* (equal contributors), Kharlyngdoh J, Das R, Molina-Jijon E, Donoro Blazquez H, Shastry S, Soria E, Wetzels J, Dijkman H, Avila-Casado C, Clement LC and Chugh SS. The zing fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases. Kidney Int. 2020 Apr;97(4):753-764. PMID:32059999
  • Del Nogal Avila M, Donoro Blazquez H,  Saha MK, Marshall CB, Clement LC,  Macé CEA, Chugh SS. Novel therapeutic approaches forchronic kidney disease due to glomerular disorders. Am J Physiol Renal Physiol. 2016;311:F63-5. PMID:27147672
  • Clement LC, Macé C, Marshall CB, Del Nogal Avila M, Chugh SS. (2015) The Proteinuria-hypertriglyceridemia connection as a basis for novel therapeutics for nephrotic syndrome. Transl Res. 165(4):499-504. PMCID: PMC4270958. PMID: 25005737
  • Macé C, Chugh SS. (2014) Nephrotic syndrome: components, connections and Angiopoietin-like 4 related therapeutics. J Am Soc Nephrol. 25(11):2393-2398. PMCID: PMC4214538. PMID:24854282
  • Chugh SS, Macé C, Clement LC, Del Nogal Avila M, Marshall C. (2014) Angiopoietin-like 4 based therapeutics for proteinuria and kidney disease. Front Pharmacol. 5:23. PMID:24611049 PDF
  • Clement LC*, Macé C* (equal contributors), Avila-Casado C, Joles JA, Kersten S, Chugh SS. (2014) Circulating Angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome. Nat Med. 20(1):37-46. PMID: 24317117 (See commentaries by Vaziri PMID: 24838183 and Kirk PMID:24342959)
  • Chugh SS, Clement LC. (2012) Telomerase at the center of collapsing glomerulopathy. Nat Med 18(1):26-27. PMID: 22227662
  • Chugh SS, Clement LC, Macé C. (2012) New insights into human minimal change disease: Lessons from animal models. Am J Kid Dis. 59(2):284-292. PMCID: PMC3253318, PMID: 21974967.
  • Avila-Casado C, Fortoul TI, Chugh SS. (2011) HIV-associated nephropathy: experimental models. Contrib Nephrol. 169:270-285. PMID: 21252526
  • Clement LC, Avila-Casado C, Macé C, Soria E, Bakker WW, Kersten S, Chugh SS. (2011) Podocyte – secreted Angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med. 17(1):117-122. PMCID: PMC3021185, PMID: 21151138
  • Clement LC, Liu G, Perez-Torres I, Kanwar YS, Avila-Casado C, Chugh SS. (2007) Early changes in gene expression that influence the course of primary glomerular disease. Kidney Int. 72(3):337-347. PMID: 17457373
  • Liu G, Clement LC, Kanwar YS, Avila-Casado C, Chugh SS. (2006) ZHX proteins regulate podocyte gene expression during the development of nephrotic syndrome. J Biol Chem. 281(51):39681-39692. PMID: 17056598
  • Liu G, Kaw B, Kurfis J, Rahmanuddin S, Kanwar YS, Chugh SS. (2003) Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability. J Clin Invest. 112(2):209-221. PMID: 12865409
  • Chugh S, Bird R, Alexander EA. Ritonavir and renal failure. N Engl J Med. 1997;336:138. PMID:8992345

Funding

National Institutes of Health grants:

  • R01DK126926 (Clement)
  • R01DK128203 (Chugh)
  • R01DK129522 (Chugh)

Our team

Dr. Camille Macé, PhD GDTL PI, supervising Joubert Kharlyngdoh, PhD, on the Typhoon Trio during a DIGE study

Research groups

Chronic kidney disease and nephrotic syndrome mechanisms


Dr. Lionel Clement, PhD, GDTL PI, on the confocal microscope

Meeting schedule: Mondays: 2 p.m.

Focused genomics and CRISPR-Cas9

Hyperlipidemia

Meeting schedule: Thursdays: 8:30 a.m.

Glycomics, proteomics and non-HIV collapsing glomerulopathy


Dr. Sumant Chugh, MD, GDTL PI, analyzing two dimension gel Western-blot
Meeting schedule: Tuesdays: 8:30 a.m.

Transcriptional regulation

Meeting schedule: Wednesdays: 8:30 a.m.

 

Contact our team

  • Glomerular Disease Therapeutics Laboratory

    Rush University Medical Center
    Cohn Research Building
    1735 W. Harrison St., Suite 436
    Chicago, IL, 60612
    Fax: (312) 563-1056
     
  • Sumant S. Chugh, MD

Cohn Research Building, Suite 406
Phone: (312) 563-1004
Email: Sumant_S_Chugh@rush.edu

  • Lionel C. Clement, PhD

Cohn Research Building, Suite 412
Phone: (312) 563-1578
Email: Lionel_Clement@rush.edu

  • Camille Macé, PhD

Cohn Research Building, Suite 412
Phone: (312) 563-1574
Email: Camille_Mace@rush.edu

  • Joubert B. Kharlyngdoh, PhD

Cohn Research Building, Suite 436
Phone: (312) 563-1571
Email: Joubert_B_Kharlyngdoh@rush.edu

  • Ranjan Das, PhD

Cohn Research Building, Suite 436
Phone: (312) 563-1571
Email: Ranjan_Das@rush.edu

  • Eduardo Molina Jijon, PhD

Cohn Research Building, Suite 436
Phone: (312) 563-1573
Email: Eduardo_MolinaJijon@rush.edu