Glomerular Disease Therapeutics Laboratory

GDTL

Glomerular Disease Therapeutics Laboratory (GDTL) develops novel Next Generation Mechanism-based Therapy for chronic kidney disease (CKD) related to glomerular disorders, malignancy-related nephrotic syndrome and multisystem disease caused by viral cytokine storms. We conduct a variety of in vivo, cell biology, proteomic, genomic, molecular biology, and imaging studies to rigorously test our scientific hypothesis. Whereas current standard-of-care drugs slow CKD progression over years, GDTL develops biological targets with multi-compartmental activity that reduces injury and promotes tissue repair to achieve CKD reversal within weeks to months. We also target keep upstream soluble mediators of kidney and multisystem disease, such as circulating cytokines, to prevent disease relapse and end organ damage.

Patented therapeutic strategies include the use of recombinant mutated human Angiopoietin-like-4 to reverse CKD, sialic acid donors for sialylation-based therapeutics, selective depletion of TNF-α or IL-6 or sIL-4Rα to prevent common cold induced relapse of MCD and FSGS, dual cytokine depletion of TNF-α with IL-2 or IL-13 or IL-4 to eliminate mortality from severe cytokine storms in rodent models, and modulation of ZHX2 expression to treat acute kidney, heart, and liver injury during acute multisystem disease.

GDTL has 4 Principal Investigators spanning 3 generations: Dr. Chugh (1st generation), 

Drs. Clement and Macé (2nd generation), and 

Dr. Molina-Jijon (3rd generation), trainee of Dr. Clement  

In Memoriam:
Caroline B. Marshall MD

GDTL News

GDTL Research seminars. To be announced

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)
  • R01DK128203 (Chugh)
  • R01DK129522 (Chugh)
  • R01DK126926 (Clement)
  • R01DK133330 (Macé)
  • R01DK141612 (Molina-Jijon, pending council review)

 

GDTL Principal Investigators

 

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

Mass spectrometry

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.

Malignancy and kidney disease

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

  • Tania Gómez-Sierra, PhD

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

  • Itzel Pamela Zavala-Guevara, PhD

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