Associate Professor
Department of Genetics and Genome Sciences
School of Medicine
Hua Lou received a Ph.D. in Plant Molecular Biology at the University of Illinois at
Urbana-Champaign in 1993. After a postdoctoral fellowship at the University of Texas M.D.
Anderson Cancer Center working with Dr. Robert Gagel, Dr. Lou moved to Baylor College of
Medicine to work with Dr. Susan Berget as an Instructor, where she continued her work on
alternative splicing. Dr. Lou joined the Department of Genetics in 2000.
I am interested in alternative RNA processing and its role in health and disease, including correction of splicing mutations in diseases.
Research Information
Research Interests
- My laboratory combines molecular genetics and RNA biology to design and test new RNA therapeutics to treat diseases. We aim to correct the disease-causing mutations at the RNA level. We are particularly interested in the mutations that disrupt pre-mRNA processing.
- Cystic Fibrosis (CF) and splicing mutations. CF is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Among more than 2000 disease causing CFTR mutations, at least 13% are mutations that lead to defective splicing. These mutations are typically located at splice sites or nearby exonic or intronic sequences. We are exploring two RNA repair strategies to correct such mutations.
- Haploinsufficiency of NF1. Neurofibromatosis type 1 (NF1) is one of the most common inheritable autosomal dominant disorders. A hallmark of the NF1 disease is its dramatically diverse clinical manifestations including tumor development, cognitive defects, bone diseases and cardiovascular dysfunction. Genetically, NF1 patients carry one constitutional null mutation in all their cells. Tumors are developed when a somatic mutation of the wild type allele is acquired in cells. However, several NF1-associated defects, such as cognitive defects and bone diseases, are caused by haploinsufficiency of the NF1 gene. There is an urgent need to investigate potential therapeutic strategies that will help the NF1 patients who suffer from any of the NF1 haploinsufficiency symptoms. We approach the question of haploinsufficiency from the perspective of RNA biology. We are exploring the possibility of increasing the NF1 gene expression using strategies that target NF1 mRNA.
- Alternative pre-mRNA splicing. My laboratory has a long history of investigating tissue- specific alternative splicing in mammals: the role of alternative splicing in development and the mechanisms that regulate tissue-specific alternative splicing. Alternative splicing plays an important role in the function of the gene product of the tumor suppressor gene, neurofibromatosis type 1 (NF1). Exon 23a of the NF1 pre-mRNA is an in-frame exon encoding 21 amino acids in the NF1 GTPase-activating protein (GAP) domain. This exon is alternatively included, producing two NF1 isoforms. The type I isoform does not contain this exon, while the type II isoform does. The ratio of the two isoforms varies in different tissues and during development. The type I isoform is predominantly expressed in neurons of the adult central nervous system and shows ten times higher activity in down-regulating Ras activity than the type II isoform. To determine how changes of NF1 alternative splicing affects the role of NF1 in development, we generated a mouse model in which the ratio of the two NF1 isoforms is drastically altered. By studying the phenotype of the mutant mice, we will gain insight into regulated exon 23a expression in the development and function of the nervous system.