research programs
medical thesis program
Ph.D. program
Research programs
Target identification program
Target validation program
Drug validation program in disease models


Target identification program

The program intends to identify new targets for the treatment of acute and chronic (renal) inflammation and autoimmunity. In this program we focus on the inflammatory mechanisms of kidney disease and autoimmune tissue injury. Our special interest focuses on factors involved in immune cell activation and migration, such as the following:

Necroinflammation:

  • NETosis as a source of DAMPs with cytotoxic effects
  • Renal cell necrosis as a source of DAMPs with immunostimulatory and cytotoxic effects
  • Proinflammatory cytokines and chemokines that trigger cell death (TNF/TNFRs, IL-1)
  • Chemokine-binding molecules as negative regulators of inflammation
  • Molecular mechanisms of crystal nephropathy
  • Molecular mechanisms of crystal-induced cell injury and kidney disease http://br.de/s/28td76f

Regeneration:

  • Cytokines and chemokines that regulate kidney regeneration (CXCL12, IL-22, etc)
  • Dendritic cell and macrophage phenotypes that determine kidney atrophy versus regeneration upon AKI
  • Sequential therapies that limit nephron loss during kidney injury
  • Cell cycle regulators as determinants of renal cell survival/loss and hypertrophy/hyperplasia in AKI/CKD

MHC-II as a target:

  • Cathepsin S as a mediator of peptide loading

Intestinal microbiota as a regulator of immunity in CKD:

  • Uremia-related dysbiosis and bacterial translocation causing systemic inflammation and immunosuppression


Top

Target validation program

The program intends to validate targets for the treatment of chronic (renal) inflammation and autoimmunity that have been identified by the target identification program. Target validation means to modulate the biological function of the target in vivo after induction of a disease model. Thus, (species-) specific agonists or antagonists for the target are required and will be used in a "therapeutical" study design (comparative study design).

Methods used in the target identification program include:

  • induction of disease models in wild-type strains,
  • administration of suitable agonists or antagonists for the target after experimental disease is established
  • Work up of tissues and specimen for primary and secondary endpoints of the study

All studies are conducted at a minimum group size and avoid any inappropriate inconvenience for the animal.
All studies are approved by the local government authorities according to German animal protection laws.

Top

Drug validation program in disease models

 

 

AKI: Models of acute nephron injury

 

     Rapid-progressive (crescentic) glomerulonephritis

  1. Heterologous nephrotoxic serum nephritis

Acute tubular injury

  1. Unilateral or bilateral renal ischemia-reperfusion injury
  2. Acute oxalate nephropathy
  3. Cisplatin-induced nephropathy
  4. Aristolochic acid-induced nephropathy
  5. Ascending urinary tract infection with uropathogenic bacteria

CKD: Models of persistent nephron loss

 

     Immune complex glomerulonephritis-mediated nephron loss

  1. Autologous nephrotoxic serum nephritis
  2. Lupus-like IC glomerulonephritis/systemic autoimmunity (MRLlpr)
  3. Lupus-like IC glomerulonephritis/systemic autoimmunity (B6lpr)
  4. Lupus-like IC glomerulonephritis/systemic autoimmunity after pristan injection (B6)

 

CKD following AKI

5. Adriamycin-induced glomerulosclerosis/nephrotic syndrome/renal fibrosis (Balb/c)

6. Long-term outcomes after unilateral renal ischemia-reperfusion injury

Genetic nephron loss

7. Alport nephropathy (collagen4A3-/-)

Metabolic nephron loss

8. Type 2 diabetes mellitus with nephropathy (db/db), usually combined with 10.

9. Sodium oxalate-rich diet-induced CKD

Surgical nephron loss

10. Renal mass ablation from uninephrectomy to 5/6 nephrectomy      

Outflow obstruction-induced nephron loss

11. Renal fibrosis after unilateral ureteral obstruction (B6)

All studies are conducted at a minimum group size and avoid any inappropriate inconvenience for the animal.
All studies are approved by the local government authorities according to German animal protection laws.

Top