Anders Grubb

Senior Professor, Physician, Legitimerad läkare

Research areas and keywords

UKÄ subject classification

  • Medical and Health Sciences
  • Medicinal Chemistry
  • Clinical Laboratory Medicine

Keywords

  • cystatin C, amyloidosis, antibiotics, renal, GFR

Research

Cystatin C and Health

Cystatin C-Based GFR-Estimating Equations and Shrunken Pore Syndrome. Development of New Drugs against Amyloidosis, Viruses and Multiresistant Grampositive Bacteria Based upon the Structure of Cystatin C.

Principal investigator; Grubb, Anders, Professor, MD/PhD

Clinical speciality: Clinical chemistry

Phone: +4646-173964

Co-workers, Lund University: Abrahamson MagnusBäck Sten-ErikBjörk JonasChristensson AndersIsaksson AndersLindström VeronicaNyman Ulf

Co-workers, not Lund University: Hansson Lars-Olof, Larsson Anders, Lerner Ulf

International networks: Franciszek Kasprzykowski, Gdansk University, Poland
Zbigniew Grzonka, Gdansk University, Poland
Regina Kasprzykowska, Gdansk University, Poland
Sylwia Rodziewicz-Motowidlo, Gdansk University, Poland
Maciej Kozak, A. Mickiewicz University, Poznan, Poland
Li Gan, University of California, USA
Mariusz Jaskolski, A. Mickiewicz University, Poznan, Poland
Efrat Levy, New York University School of Medicine, USA
Ingrid Zegers, European Commission, IRMM, Geel, Belgium
Søren Blirup-Jensen, Alk-Abello Inc., Copenhagen, Denmark
Harald Althaus, Siemens Inc., Marburg, Germany

Research area/areas: Biomedical Laboratory Science/TechnologyClinical Laboratory MedicineGeneral MedicineMedicinal ChemistryMicrobiology in the medical areaOther Clinical Medicine

We sequenced in 1981 a protein with unknown function, now called cystatin C, which defined a new superfamily of cysteine protease inhibitors ("cystatins"). We have described several new cystatins and shown that cystatin C is produced by a house-keeping gene and that a mutation in it causes the dominantly inherited disease "Hereditary Cystatin C Amyloid Angiopathy" in which L68Q-cystatin C is precipitated as amyloid in affected individuals, who die from brain hemorrhage before 40 years of age. We have demonstrated that cystatin C amyloid deposits may form by "propagated domain-swapping" and shown that inhibition of domain swapping prevents the in vitro formation of cystatin C amyloid. We have also demonstrated that cystatin C modulates the amyloid deposits in Alzheimer disease. We have demonstrated that certain peptidyl derivatives based upon the structure of cystatin C will kill grampositive bacteria resistant to all known presently available antibiotic compounds and some viruses. We demonstrated in 1984 that the serum level of cystatin C probably is a better marker for glomerular filtration rate than creatinine. We produced an international calibrator for cystatin C in 2010.

We will produce low molecular mass compounds preventing domain swapping of cystatin C by a molecular dynamics approach and by high-throughput screening of drug libraries. 
We will, in addition, try to elucidate the antibacterial and antiviral mechanisms of cystatin-based antibacterial and antiviral compounds in an effort to create a new class of clinically useful antibacterial substances.
We will try to identify those clinical situations in which serum cystatin C will be a particularly important marker for specific renal dysfunction in an effort to substitute non-invasive for invasive diagnostic procedures for kidney disease. We will produce an assay-independent cystatin C-based GFR prediction equation.

Development of drugs against amyloid disorders and multiresistant bacteria may allow treatment of presently incurable disease states. Improved GFR-prediction equations will allow better evaluation of renal disease and safer dosing of drugs and contrast media excreted via the kidneys.

Link to project homepage: http://www.egfr.se

5 recent original publications

Östner Gustav, Lindström Veronica, Christensen Per Hjort, Kozak Maciej, Abrahamson Magnus, Grubb Anders
Stabilization, characterization, and selective removal of cystatin C amyloid oligomers
J. Biol. Chem.. 2013; 288: 16438-16450

 

Grubb Anders
Non-invasive estimation of glomerular filtration rate (GFR). The Lund model: Simultaneous use of cystatin C- and creatinine-based GFR-prediction equations, clinical data and an internal quality check.
Scand. J. Clin. Lab. Invest.. 2010; 70: 65-70

 

Wahlbom Maria, Wang Xin, Lindström Veronica, Carlemalm Eric, Jaskolski Mariusz, Grubb Anders
Fibrillogenic oligomers of human cystatin C are formed by propagated domain swapping.
Journal of Biological Chemistry. 2007; 282: 18318 - 18326

 

Wahlbom Maria, Wang Xin, Rodziewicz-Motowidlo Sylwia, Janowski Robert, Lindström Veronica, Önnerfjord Patrik, Westermark Gunilla, Grzonka Zbigniew, Jaskolski Mariusz, Grubb Anders
Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C. Use of engineered disulfide bridges, antibodies and carboxymethylpapain to stabilize the monomeric form of cystatin C.
J. Biol. Chem.. 2004; 279: 24236 - 45

 

Jasir Med Dr, Ph.d Aftab, Kasprzykowski Franciszek, Kasprzykowska Regina, Lindström Veronica, Schalén M.D., Ph.D. Claës, Grubb Anders
New antimicrobial cystatin C-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus and multiresistant coagulase-negative staphylococci.
APMIS. 2003; 111: 1004 - 1010

Recent research outputs

Taube, M., Pietralik, Z., Szymanska, A., Szutkowski, K., Clemens, D., Anders Grubb & Kozak, M., 2019 Jun 12, In : Scientific Reports. 9, 1, 8548.

Research output: Contribution to journalArticle

Anders Grubb, 2019 May 28, In : Lakartidningen. 116

Research output: Contribution to journalReview article

Dzierżyńska, M., Sikorska, E., Pogorzelska, A., Mulkiewicz, E., Sawicka, J., Wyrzykowski, D., Małuch, I., Anders Grubb, Kasprzykowski, F. & Rodziewicz-Motowidło, S., 2019 Mar 11, In : Protein and Peptide Letters.

Research output: Contribution to journalArticle

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