Degrees and Certifications:
BSc, PhD

Rank and Title:
Professor

Department:
Department of Immunology/Microbiology

Endowed Professorship:

Office Location:
1750 West Harrison Street
Chicago, IL 60612

Laboratory Location:
Jelke Building Room 858
1750 West Harrison Street
Chicago, IL 60612

Phone:
312-942-2287

Fax:

E-mail:
spkwan@rush.edu

Education:
BSc, McGill University, Montreal , Canada
PhD, University of Cincinnati, Cincinnati, Ohio

Research Areas:

Laboratory Techniques:

Hyperlinks:

Documents:

Faculty/Staff Description:
The research interests of this laboratory are centered on mapping, cloning and identifying genes that are responsible for immunologic dysfunction or developmental abnormalities in the brain.

We have studied the molecular basis of two recessive X-linked immunodeficiencies: Wiskott-Aldrich syndrome (WAS) and X-linked agammaglobulinemia (XLA). XLA is caused by a primary defect in B-lymphocytes and manifests through recurrent pyogenic infections. We initially mapped the disease locus for XLA to the long arm of the human X-chromosome on Xq21.3 and subsequently cloned the gene. This gene consists of 19 exons covering 37kb. The corresponding 2.6kb mRNA transcript encodes a src related cytoplasmic protein tyrosine kinase designated Btk (Bruton's agammaglobulinemia tyrosine kinase). PCR based assays have been developed in this laboratory to study the mutations in these patients.

The Wiskott-Aldrich syndrome (WAS) is characterized by overwhelming infections, thrombocytopenia, and eczema. The locus for WAS was mapped by our group to the short arm of the human X-chromosome at Xp11.23. We were one of two laboratories that identified the gene responsible for WAS through positional cloning. This gene is 8kb in length and has 12 exons encoding a 2kb mRNA. The WAS protein (WASP) exhibits four functional domains including a PH domain at the N terminus, a GTPase binding domain, a polyproline rich SH3 binding region, and finally two actin binding regions at the C terminus. WASP is thought to regulate actin polymerization, and our current research involves the further elucidation of WASP function in the molecular mechanisms underlying the immune disorder. In addition, we have continued to physically map and clone genes in the region of Xp11.22-Xp11.23.

We are presently investigating the genetic etiology of other immune system defects through genetic mapping and positional cloning to eventually identify and isolate the unknown culprit genes. Finally, we are also studying the genes that affect neurodevelopment and lead to the pervasive developmental disorder of autism. Linkage analysis followed by the identification of mutations or polymorphisms in candidate genes will lead to a better understanding of this complex disorder. Furthermore, we are studying the variation in gene expression patterns in autistic versus normal individuals.

Selected Publications:
Hagemann TL, Y Chen, FS Rosen, and S-P Kwan. (1994). Genomic organization of the BTK gene and exon scanning for mutations in patients with X-linked agammaglobulinemia. Hum. Mol. Genet. 3: 1743-1749.

Kwan S-P, TL Hagemann, BE Radtke, RM Blaese, and FS Rosen. (1995). Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene. Proc. Natl. Acad. Sci. USA 92: 4706-4710.

Kwan S-P, TL Hagemann, RM Blaese, and FS Rosen, (1995). A high resolution map of genes, microsatellite markers, and new dinucleotide repeats from UBE1 to the GATA locus in the region Xp11.23. Genomics 29: 247-252.

Remold-O'Donnell E, J Cooley, A Shcherbina, TL Hagemann, S-P Kwan, DM Kenney, and FS Rosen. (1997). Variable expression of WASP in B cell lines of Wiskott-Aldrich syndrome patients. J. Immunology 158: 4021-4025.

Snapper SB, FS Rosen, E Mizoguchi, P Cohen, W Khan, C-H Liu, TL Hagemann, S-P Kwan, R Ferrini, L Davidson, AK Bhan, and FW Alt. (1998). Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9: 81-91.

Hagemann TL and S-P Kwan. (1999). The identification and characterization of two promoters and the complete genomic sequence for the Wiskott-Aldrich syndrome gene. Biochem Biophys. Res. Comm. 256: 104-109.