Faculty Biography

Dr. Kit Sing (Paul) Au, Ph.D.

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Education:

Ph.D., Baylor College of Medicine, Houston, Texas

M.Phil, Microbiology, Chinese University of Hong Kong

B.S., Biology, Chinese University of Hong Kong

Clinical and Research Interests:

1. Tuberous sclerosis complex
2. Neural tube defects

Au KS -- Research interests Our laboratory researches focus on two human genetic diseases: tuberous sclerosis complex and neural tube defects.

Tuberous sclerosis complex (TSC) is a human dominantly inherited disease. Loss of function of TSC genes predisposes patients to hamartomas and hamartias formation in virtually every organ system. Other disease symptoms include seizure, learning disability and mental retardation. Two genes have been identified to cause the diseases and they are TSC1 on 9q34.3 and TSC2 on 16p13.3. The gene products, tuberin and hamartin, were recently identified to regulate signaling pathways including the mTOR/Akt/PKB, the Wnt/GSK3/-catenin, AMPK and possibly the activity of cdk2/cdk4/cdk6 activities through nuclear localizing of active p27Kip1. TSC2 gene product, tuberin, could potentially participate in these signaling pathways involving growth factors, nutrients, ions, DNA damage and repair. The function of the TSC1 gene product, hamartin, has an ERM domain and a coiled-coil domain important for protein dimerization. Recently, interaction of hamartin with neurofilament light chain has been demonstrated suggesting a possible role of hamartin in cytoskeletal scaffold formation and possibly intracellular vesicle transportation.

Interestingly, clinical symptoms vary widely among patients with TSC from genotype-phenotype correlation studies. We used cDNA expression microarray technologies to obtain global gene expression patterns from hamartomas isolated from patients with TSC and identified genes with altered expressions. We are examining these factors for their involvement in the clinical presentations among TSC patients.

We have developed a direct sequencing protocol to identify pathogenic mutation for 300 patients. Currently we are developing an array based comparative genomic hybridization (CGH) protocol to identify patients with large deletions and an endonuclease based mis-match/repair protocol to identify patients with mosaicism.

The second major project in the laboratory is applying our experience in mapping TSC genes to map genes involving in neural tube defects (Spina Bifida, SB, in particular). Since Hispanic descents appear to have higher risks of SB in the US, we are specifically interested in identifying genes that contribute to the higher SB risk in these ethnic groups. A candidate gene testing approach is adopted using various genetic markers (STR, RFLP, and SNPs). We demonstrated significant risk of SB were associated with several genes (e.g. MTHFR, FLOR1, GRHL3, FGF1, BRCA1 and CBP) among our patients.

Publications (selected):

• Northrup H, Au KS: Tuberous sclerosis complex, GeneClinics, University of Washington, Pagon RS (ed.). Web site: http://www.geneclinics.org/profiles/tuberoussclerosis/index.html. Updated 2005.
• Au KS, Northrup H, Kirkpatrick TJ, Volcik KA, Fletcher JM, Townsend IT, Blanton SH, Tyerman GH, Villarreal G, King TM: Promotor genotype of the platelet derived growth factor receptor alpha gene shows population stratification but not associated with spina bifida meningomyelocele. Am J Med Genet 139A(3):194-198, 2005.
• Woerner AC, Au KS, Williams AT, Harris PC, Northrup H: Tuberous sclerosis complex and polycystic kidney disease: an exception to the contiguous gene syndrome. Genet in Med 8(3):197-198, 2006.
• King TM, Au KS, Kirkpatrick TJ, Fletcher JM, Townsend I, Tyerman GH, Shimmin LC, Northrup H. The Impact of BRCA1 on Spina Bifida Meningomyelocele Lesions. Ann of Hum Genet (submitted) [first two authors contributed equally] 2006.
• Kozlowski P, Roberts P, Dabora S, Franz D, Bissler J, Northrup H, Au KS, Lazarus R, Domanska-Pakiela D, Kotulska K, Jozwiak S, Kwiatkowski DJ. Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Amer J Hum Genet (submitted) 2006.
• Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR, Wheless JW, Baumgartner JE, Roa BB, Wilson AM, Smith-Knuppel TK, Cheung MC, Whittermore VH, King TM, Northrup H. Genotype/Phenotype Correlation in 325 Individuals Referred for a Diagnosis of Tuberous Sclerosis Complex in United States. Genetics in Medicine (submitted) 2006.
• Kozlowski P, Roberts P, Dabora S, Franz D, Bissler J, Northrup H, Au KS, Lazarus R, Domanska-Pakiela D, Kotulska K, Jozwiak S, Kwiatkowski DJ. Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. The American Society of Human Genetics 56th Annual Meeting, New Orleans, Louisiana, October 2006.

 

Location & Contact

6431 Fannin Street
MSB 3.020
Houston, Texas 77030
713-500-5757 (Voice)

Faculty Biography

• Dr. Kit Sing (Paul) Au, Ph.D.
  Assistant Professor and Division Head
• Department of Pediatrics
  Division of Genetics
• University of Texas-Houston Medical School
  6431 Fannin Street, MSB-3.518
  Houston, Texas 77030
• phone: (713) 500-5769
  fax: (713) 500-5789
  e-mail: Kit-Sing.Au@ uth.tmc.edu
• Executive Assistant:
  Susan Ramos | 713.500.5663