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Welcome to the Joslin Research Website                     
 
  Joslin Investigator:
   
  
Dr. Andrzej S. Krolewski
 
Investigator Specifics:
Professional Details:
Publications
CV not available

Member of Section:
Genetics and Epidemiology

Core Director:

Enrichment Program

Current Fellows, Students, or Lab Members:
Bozena Krolewski, PhD
Boguslaw Lipinski, PhD
Monika Niewczas, M.D., Ph.D.
Marcus Pezzolesi
Grzegorz Placha
Krzysztof Wanic

Past Fellows, etc.:
Shin-ichi  Araki
Jacek Bochenski
Luis Canani
Tomasz Klupa
Yuichiro Makita
Terumasa Nagase
Moon-Suk  Nam
Daniel Peng Keat Ng
Bruce Perkins
Laura Scott
Pawel Wolkow


 
 
Andrzej S Krolewski, MD, PhD
Investigator
Joslin Diabetes Center
Section Head: Genetics and Epidemiology
Joslin Diabetes Center
 
6/11/1980 -  
 
 Tracking Down Factors Leading to Complications in Diabetes

As Head of the Genetics and Epidemiology Section for the past two decades, Andrzej S. Krolewski, M.D., Ph.D., has established a world-class research program on the genetics and epidemiology of diabetes and its complications, based on data from Joslin Clinic patients and their relatives.

Dr. Krolewski’s research has contributed particularly to the understanding of the mechanisms of diabetic kidney disease, also referred to as diabetic nephropathy, and to the genetics of type 2 diabetes. His current research encompasses three areas.

The first is a continuation of his long-term investigation of the genetics of diabetic nephropathy. He and his collaborators have demonstrated that this complication develops primarily in patients with a genetic predisposition. The data supporting this hypothesis are equally strong in type 1 and type 2 diabetes. Dr. Krolewski now has evidence that there are two to three genes that make people susceptible to this complication. This susceptibility may impact the development of glomerular or tubular or interstitial abnormalities. His current research focuses on identifying these genes, and once identified, studying their role in the etiology of diabetic nephropathy. This research should lead to the discovery of new metabolic pathways underlying this susceptibility; these pathways will then be used as targets for the development of therapeutic strategies.

The second research area concerns his finding that one-third of patients with diabetes and microalbuminuria (slight amounts of protein in the urine) start losing renal function very early, many years before they develop overt proteinuria (high amounts of protein in the urine). Using current proteomic technologies, Dr. Krolewski and his colleagues are examining urinary proteins to (1) develop diagnostic tests to recognize patients with early renal function decline and (2) implement interventions to prevent or retard loss of renal function while these patients still have normal renal function.

The third research area of Dr. Krolewski’s laboratory is the genetics of type 2 diabetes. He and his collaborators discovered that mutations in NEUROD-1 contribute to the development of type 2 diabetes in young individuals (called maturity-onset diabetes of the young, or MODY). Currently, they have been focusing on identifying a gene on chromosome 20q that may be responsible for susceptibility to type 2 diabetes in families where the disease is characterized by onset in middle age, obesity and insulin resistance.


Selected References:

Pezzolesi MG, Nam M, Nagase T, Klupa T, Dunn JS, Mlynarski WM, Rich SS, Warram JH, Krolewski S. Examination of candidate chromosomal regions for type 2 diabetes reveals a susceptibility locus on human chromosome 8p23.1 Diabetes 53; 486-491, 2004.

Araki S, Ng DP, Krolewski B, Wyrwicz L, Rogus JJ, Canani L, Makita Y, Haneda M, Warram JH, Krolewski AS. Identification of a common risk haplotype for diabetic nephropathy at the protein kinase C-beta (PRKCB1) gene locus.
J Am Soc Nephrol 14:2015-2024, 2003.

Klupa T, Malecki MT, Pezzolesi M, Ji L, Curtis S, Langefeld CD, Rich SS, Warram JH, Krolewski AS. Further evidence for a susceptibility locus for type 2 diabetes mellitus on chromosome 20q13.1-q13.2. Diabetes 49:2212-2216, 2000.

Fogarty DG, Rich SS, Hanna L, Warram JH, Krolewski AS. Urinary albumin excretion in families with NIDDM is heritable and genetically correlated to blood pressure.
Kidney Int 57:250-257, 2000.

Malecki MT, Jhala US, Antonellis A, Fields L, Saad M, Doria A, Warram JH, Montminy M, Krolewski AS. Mutations in NEUROD1/BETA2 are associated with the development of type 2 diabetes mellitus. Nat Genet 23:323-328, 1999.

Krolewski AS. Genetic susceptibility to diabetic nephropathy - Evidence for major and minor gene effects. Kidney Int 1999; 55:1582-96


Biographical Sketch:

Dr. Krolewski heads the Section on Genetics and Epidemiology and is an Associate Professor of Medicine at Harvard Medical School. He received his medical degree and doctorate in Epidemiology from Warsaw Medical University in Poland. He obtained training in diabetes research at Joslin Diabetes Center and in molecular human genetics at the Center for Cancer Research at the Massachusetts Institute of Technology.