Professor, Department of Molecular and Human Genetics
Director, Mitochondrial Laboratory

B.S., National Taiwan University, 1971
Ph.D., Ohio State University, 1975
Postdoc, Princeton University, 1976

RESEARCH INTERESTS:

My primary research interest lies in the understanding of mitochondrial genetics and function in disease, cancer, and aging. For many years our laboratory has had its major contribution to the improvement of the molecular diagnosis of mitochondrial disorders. This includes the development of comprehensive mutation detection methods, a one-step real time quantitative PCR technique for the detection and quantification of heteroplasmic point mutations, mutational analysis of the whole mitochondrial genome, and simultaneous detection of mtDNA deletions and mtDNA copy numbers. We validate the qPCR method for the quantification of mtDNA content in various tissues including muscle, liver, and skin of control and patients with mtDNA depletion syndrome. Since the majority of the mitochondrial disorders are caused by nuclear gene defects, we constantly develop new assays to identify nuclear gene defects that are involved in the assembly of the respiratory chain complexes or the biogenesis of mitochondria. Novel mutations are continuously being identified in genes responsible for mtDNA depletion syndrome, including thymidine phosphorylase, deoxyguanine kinase genes, DNA polymerase gamma, thymidine kinase 2, MPV17, DNA helicase, SUCLG, and SUCLA. We are currently studying molecular and biochemical mechanisms that lead to mtDNA depletion and disease phenotype.

Oxidative stress is a major risk factor in aging and cancer. Mitochondria play an indispensable role in the production and scavenging of reactive oxygen species (ROS). We believe both germline variations and somatic mutations in mitochondrial DNA have crucial effects on mitochondrial function and thus oxidative stress of an individual. Studies of tumor/normal tissue pairs have identified somatic mtDNA mutations in all types of tumors. Since dysregulation of metabolism is the hallmark of cancer formation, and mitochondria play a key role in energy metabolism, it is important to understand the mitochondrial function in cancer cells. By using transmitochondrial cybrid cells (fusion of mitochondria derived from cancer cells with normal cells depleted of mtDNA), we are able to demonstrate that the tiny 16.6 kb mitochondrial genome is capable of modulating vast nuclear gene expression as shown in expression array and mitochondrial respiratory chain studies. These results support that the cross-talk between the two genomes is bi-directional.

Germline mtDNA variations and haplogroups may be modifying factors for cancer predisposition. We have genotyped 78 mtDNA variations in over 200 females with breast cancer and 200 healthy females. The results of haplogroup and phylogenetic analyses showed that individuals with haplogroup K demonstrated a significant increase in the risk of breast cancer; whereas, individuals bearing haplogroup U had a significant decrease in the risk of breast cancer. Furthermore, some ndividual variations showed a significant protective effect; while others showed significant increase in breast cancer risk. Thus, our results suggest that mitochondrial DNA haplotypes and variations play a role in modifying an individual’s risk to breast cancer. Our research also includes the investigation of genetic and functional roles of mitochondria in diabetes, hypertension, and metabolic syndrome.

SELECTED PUBLICATIONS:

1. Dimmock DP, Dunn JK, Feigenbaum A, Rupar A, Horvath R, Freisinger P, Mousson de Camaret, Wong LJ, Scaglia F (2008). Abnormal neurological exam predicts poor survival and should precluded liver transplantation in deoxyguanosine kinase deficiency. Liver Transpl., in press.

2. Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC (2008). Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Hum. Mutat. Jun 10. [Epub ahead of print]

3. Wong LJ, Dimmock D, Geraghty MT, Quan R, Lichter-Konecki U, Wang J, Brundage EK, Scaglia F, Chinault AC (2008). Utility of oligonucleotide array-based comparative genomic hybridization for detection of target gene deletions. Clin. Chem. 54: 1141-1148.

4. Dimmock DP, Zhang Q, Dionisi-Vici C, Carrozzo R, Shieh J, Tang LY, Truong C, Schmitt E, Sifry-Platt M, Lucioli S, Santorelli FM, Ficicioglu CH, Rodriguez M, Wierenga K, Enns GM, Longo N, Lipson MH, Vallance H, Craigen WJ, Scaglia F, Wong LJ (2008). Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase. Hum. Mutat. 29: 330-331.

5. Scaglia F, Wong LJ (2008). Human mitochondrial transfer RNAs: role of pathogenic mutation in disease. Muscle Nerve 37: 150-171. Review.

6. Bai RK, Leal SM, Covarrubias D, Liu A, Wong LJ (2007). Mitochondrial genetic background modifies breast cancer risk. Cancer Res. 67: 4687-4694.

7. Wong LJC, Brunetti-Pierri N, Zhang Q, et al. (2007). Mutations in the MPV17 gene are responsible for rapidly progressive liver failure in infancy. Hepatology 46: 1218-1227.

8. Wong LJC (2007). Pathogenic mitochondrial DNA mutations in protein coding genes. Invited Review Article. Muscle Nerve 36: 279-293.

9. Bai R, Wong LJ (2006). Simultaneous detection and quantification of mitochondrial DNA deletion, depletion, and amplification in patients with mitochondrial disease. J. Mol. Diag. 7: 613-622.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Lee-Jun C. Wong, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-1940
Fax: 713-798-8937
E-mail:

Back to top