Positions

Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US
Vice President, Sr. Lab Director
Baylor Miraca Genetics Laboratories
Professor
Program in Translational Biology & Molecular Medicine
Baylor College of Medicine

Education

PhD from Ohio State University
Postdoctoral Fellowship at Princeton University
BS from National Taiwan University

Certifications

Clinical Biochemical Genetics
American Board of Medical Genetics
Clinical Molecular Genetics
American Board of Medical Genetics

Professional Interests

  • Mitochondrial genetics and function in human diseases, cancer, and aging

Professional Statement

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 the complex dual genome mitochondrial disorders. This includes the development of various molecular technologies to detect and quantify heteroplasmic mtDNA mutations, including point mutations and deletions, as well as detection of copy number changes (CNVs) in both mitochondrial and nuclear genomes. We developed a dense oligonucleotide array CGH (MitoMet array) targeted to coding exons of nuclear and mitochondrial genes related to mitochondrial and metabolic disorders for the detection of nuclear and mtDNA deletions. More recently, using one pair of back-to-back primers to amplify the intact circular mitochondrial genome followed by deep massively parallel sequencing, we were able to detect and accurately quantify mtDNA point mutations at any nucleotide positions of the mitochondrial genome without the interference of nuclear mitochondrial DNA homologous sequences. In addition, the breakpoints of mtDNA single and multiple deletions can be unequivocally determined. Using target gene capture and deep next generation sequencing (NGS) technology, we have validated a series of NGS-based panel testing for clinical diagnostic utilities. These include groups of genes involved in specific metabolic pathways, such as glycogen storage disease (GSD) and congenital disorders of glycosylation (CDG); disease with defined clinical phenotype (eg Usher syndrome); genetically heterogeneous diseases involved a particular organ (eg eye, bone); and genetically and clinically heterogeneous mitochondrial disorder, in addition to complex neuromuscular disorders. We developed analytical pipeline to simultaneously detect point mutations (SNVs) and exonic deletions (CNVs) using the same set of NGS sequence data.

Reprogramming of energy metabolism is one of the hallmarks of cancer. In proliferating cancer cells, the rates of glycolysis, lactate production, and biosynthesis of lipids and other macromolecules are increased. This Warburg effect is attributed to defective or re-programmed mitochondrial energy metabolism in cancer cells. My research interest is to investigate the mechanism of the interplay between the nuclear and mitochondrial genomes and to identify key modulators in the dual genome cross-talk that impact cellular energetics. We established transmitochondrial cybrids with a defined nuclear background containing mitochondria derived from cancer cell lines with various degrees of tumorigenicity and metastatic potency to investigate the functional effect of cancer mitochondria on nuclear gene expression and to provide insight into the mechanism of mitochondrial-nuclear cross-talk as well as the relationship between energy metabolism and cancer development.

Selected Publications