Glomerular Disease Therapeutics Laboratory

Glomerular therapeutics lab team

Our primary goal at the Glomerular Disease Therapeutics Laboratory is to develop novel mechanism based therapy for proteinuria and chronic kidney disease related to glomerular disorders. 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. Novel therapeutic strategies in advanced stages of development include the use of compounds that alter sialylation  in vivo, and various forms of recombinant Angiopoietin-like-4 in the treatment of some forms of nephrotic syndrome (see patents below). We are actively engaged in identifying a circulating glomerulophilic proteome (CGP) and exploring the role of the zinc fingers and homeoboxes (ZHX) family of proteins in the pathogenesis and modulation of glomerular disease.

GDTL News!

  1. GDTL investigators join the scientific community to congratulate Dr. Max Cooper for receiving the 2019 Lasker Award for research leading to the discovery of B cells. GDTL PI Dr. Chugh, who received the Max Cooper Award for Outstanding Research in 2012, has collaborated with Dr. Cooper since 1999 on the biology of Aminopeptidase A, a transmembrane protein expressed in immature B cells and kidney cells. 
  2. Maria Del Nogal Avila PhD, senior postdoctoral fellow at GDTL since 2013, joined a fully funded position as Assistant Professor at San Pablo CEU University in Madrid, Spain on September 1 2019. Maria has 50% protected research time, and will continue her work on the molecular mechanisms of nephrotic syndrome in her independent laboratory. 
  3. Eduardo Molina-Jijon PhD, postdoctoral fellow with GDTL PI Dr. Clement, received First Place in the poster competition during the 5th Annual Mentoring Programs Symposium at Rush University in September 2019.

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. Provisional filed through Rush University July 2018, PCT filed July 2019. 

Selected publications

  • Camille Macé*, Maria Del Nogal Avila*, Caroline B. Marshall* (equal contributors), Joubert Kharlyngdoh, Ranjan Das, Eduardo Molina-Jijon, Hector Donoro Blazquez, Suresh Shastry, Elisabeth Soria, Jack Wetzels, Henry Dijkman, Carmen Avila-Casado, Lionel C. Clement and Sumant S. Chugh. ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases. Kidney Int. Nov 2019 (In press).
  • 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:

  • R01DK101637 (Chugh)
  • R01DK109713 (Chugh, Clement)
  • R01DK111102 (Chugh, Macé)

American Heart Association grant:

  • 16SDG27500017 (Macé)
     

Our team

  • Sumant S. Chugh, MBBS, MD, principal investigator

    Dr. Camille Macé, PhD GDTL PI, supervising Joubert Kharlyngdoh, PhD, on the Typhoon Trio during a DIGE study
  • Lionel C. Clement, PhD, principal investigator
  • Camille Macé, PhD, principal investigator
  • Joubert B. Kharlyngdoh, PhD, postdoctoral fellow
  • Ranjan Das, PhD, postdoctoral fellow
  • Pascal Bus, PhD, postdoctoral fellow
  • Zoë Post, MD, postdoctoral fellow
  • Eduardo Molina Jijon, PhD, postdoctoral fellow
  • Stephanie Gambut, MSc, research technician
  • Malu Zandbergen, BSc, research technician

Research groups

Proteinuria, chronic kidney disease, nephrotic syndrome mechanisms


Dr. Lionel Clement, PhD, GDTL PI, on the confocal microscope
  • Sumant S. Chugh, MD
  • Joubert B. Kharlyngdoh, PhD
  • Ranjan Das, PhD
  • Pascal Bus, PhD
  • Zoë Post, MD
  • Malu Zandbergen, BSc

Meeting schedule: Mondays: 2 p.m.

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., 436 and 441
    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 420
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 441
Phone: (312) 563-1568
Email: Ranjan_Das@rush.edu

  • Pascal Bus, PhD

Cohn Research Building, Suite 441
Phone: (312) 563-1568
Email: Pascal_Bus@rush.edu

  • Zoë Post, MD

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

  • Eduardo Molina Jijon, PhD

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

  • Stephanie Gambut, MSc

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

  • Malu Zandbergen, Bsc

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