Glomerular Disease Therapeutics Laboratory

Three researchers

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 storms.

In Memoriam:
Caroline B. Marshall MD

GDTL News

Research Unveils Paths to Stopping Cytokine Storms in COVID-19 (newswise.com)

 

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 of treating the effects of cytokine storms. PCT/US22/47254.
  • Methods of improving systemic disease outcomes by inhibition of ZHX2. PCT/US22/47263.

 

Selected publications

  • Chugh SS, Clement LC. “Idiopathic” Minimal Change nephrotic syndrome: A podocyte mystery nears the end. Am J Physiol Renal Physiol. 2023 Dec 1;325(6):F685-F694. PMID: 37795536
  • Del Nogal Avila M*, Das R*, Kharlyngdoh J*, Molina-Jijon E* (equal contributors), Donoro Blazquez H, Gambut S, Crowley M, Crossman DK, Gbadegesin RA, Chugh SS, Chugh SS, Avila-Casado C, Macé C, Clement LC and Chugh SS. Cytokine storm based mechanisms for extra-pulmonary manifestations of SARS-CoV-2 infection. JCI Insight 2023 May 22;8(10):e166012. PMID: 37040185  PMCID: PMC: 10322692
  • 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 zinc 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 for chronic 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

Two scientists carefully work with pipettes in a lab.

National Institutes of Health grants:

  • R01DK137919 (Chugh & Clement)
  • R01DK133330 (Macé)
  • R01DK126926 (Clement)
  • R01DK128203 (Chugh)
  • R01DK129522 (Chugh)

 

Our team

  • Sumant S. Chugh, MBBS, MD, principal investigator
  • Lionel C. Clement, PhD, principal investigator
  • Camille Macé, PhD, principal investigator
  • Eduardo Molina Jijon, PhD, instructor
  • José Luis Sánchez Gloria, PhD, postdoctoral fellow
  • Ariadna Jazmín Ortega Lozano, PhD, postdoctoral fellow
  • Carmen Avila-Casado, MD, PhD, University of Toranto, Canada (Collaborator)

 

Research groups

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

Chronic kidney disease and nephrotic syndrome mechanisms

Focused genomics and CRISPR-Cas9

Hyperlipidemia

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

Glycomics, proteomics and non-HIV collapsing glomerulopathy

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

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

Transcriptional regulation

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

COVID-19-related CKD progression

 

Contact our team

Dr. Sumant Chugh, MD, GDTL PI, analyzing two dimension gel Western-blot

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

  • Eduardo Molina Jijon, PhD

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

  • José Luis Sánchez Gloria, PhD

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

  • Ariadna Jazmin Ortega Lozano, PhD

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