John H Wilson, Ph.D.
Distinguished Service Professor
Positions
- Distinguished Service Professor
-
Biochemistry-Wilson Lab
Baylor College of Medicine
Houston, TX, US
Addresses
- BCM-Ben Taub Research Center (Office)
-
Room: BCMT-T342
Houston, TX, 77030
United States
Education
- Advanced Training from Stanford University
- 01/1971 - Stanford, CA, United States
- PhD from California Institute Of Technology
- 01/1971 - Pasadena, CA, United States
- AB from Wabash College
- 01/1966 - Wabash, IN, United States
Honors & Awards
- Marc Dresden Excellence in Education Award
- This award is given to individuals who consistently make great contributions to graduate education as distinguished teachers and advisors.
- Baylor College of Medicine (10/2013)
- Eight Strand Beta-Barrel Jelly Roll Award
- Baylor College of Medicine (01/2007)
- Eight Strand Beta-Barrel Jelly Roll Award
- Baylor College of Medicine (01/2005)
- Eight Strand Beta-Barrel Jelly Roll Award
- Baylor College of Medicine (01/2004)
- Barbara and Corbin Robertson Presidential Teaching Award for Excellence in Teaching
- Baylor College of Medicine (01/1999)
- John P. McGovern Teaching Award
- Baylor College of Medicine (01/1998)
- Excellence in Teaching Award, Nurse Midwifery Program
- Baylor College of Medicine (01/1998)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1998)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1997)
- Master Teacher’s Fellowship Program
- Baylor College of Medicine (01/1995 - 01/1997)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1995)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1994)
- John P. McGovern Teaching Award
- Baylor College of Medicine (01/1993)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1993)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1992)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1992)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1991)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1990)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1986)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1985)
- Outstanding Teacher Award
- Baylor College of Medicine (01/1984)
- Distinguished Faculty Award
- Baylor College of Medicine (01/2001)
Professional Interests
- Mouse and Rat
- Neural Plasticity and Degeneration
- Gene Therapy
- Chromosomes, Chromatin, and DNA Biology
- Development and Evolution
- Molecular Basis of Human Disease and Behavior
Professional Statement
We are interested in two, complementary aspects of genome biology: defining the pathways that control the stability of disease-causing trinucleotide repeats, and developing methods to accomplish precise gene modifications for gene therapy. We are exploring these interests in the context of inherited human neurological diseases.
Instability of Trinucleotide Repeats
Expansions of trinucleotide repeats in specific human genes cause several neurodegenerative diseases such as Huntington disease and myotonic dystrophy. The basis for repeat instability—their ability to expand and contract the number of repeats in a tract—is unclear. To define these mechanisms, we have developed exquisitely sensitive assays that detect repeat instability in mammalian cells. These assays reveal that CAG repeats are dramatically destabilized by transcription through the repeat, by genome-wide demethylation, and by environmental stresses such as hypoxia, heat shock, cold shock, and oxidative stress.
By knocking down expression of specific genes in human cells with siRNAs, and using gene mutations in mice, we are identifying the roles of various genes and DNA metabolic processes that are responsible for repeat instability. In addition, we are optimizing the use of zinc-finger nucleases that introduce double-strand breaks into CAG repeats, and zinc-finger nickases that introduce single strand breaks, as reagents to shrink long CAG tracts as a potential therapy for human patients.
Targeted Genome Modification
Retinitis pigmentosa (RP), which affects 1 in every 3000 people worldwide, typically begins with loss of peripheral vision in the teens and progresses to tunnel vision and blindness in middle age. We are developing gene-specific strategies for genome modification, with the ultimate aim of treating this disease in humans. Dominant mutations in the rhodopsin gene are the largest single cause of RP.
To develop treatment protocols, we have generated mouse models in which one copy of the mouse rhodopsin gene is replaced with one or another forms of the human rhodopsin gene fused to GFP. These fluorescently tagged mouse models provide convenient color markers for the assessment of treatment efficacy. We are using these mouse models to test and optimize various gene specific cleavage reagents such as zinc-finger nucleases for their ability to correct or knockout defective genes. These studies will also elucidate the DNA repair capabilities of terminally differentiated neurons, which are currently undefined.
Instability of Trinucleotide Repeats
Expansions of trinucleotide repeats in specific human genes cause several neurodegenerative diseases such as Huntington disease and myotonic dystrophy. The basis for repeat instability—their ability to expand and contract the number of repeats in a tract—is unclear. To define these mechanisms, we have developed exquisitely sensitive assays that detect repeat instability in mammalian cells. These assays reveal that CAG repeats are dramatically destabilized by transcription through the repeat, by genome-wide demethylation, and by environmental stresses such as hypoxia, heat shock, cold shock, and oxidative stress.
By knocking down expression of specific genes in human cells with siRNAs, and using gene mutations in mice, we are identifying the roles of various genes and DNA metabolic processes that are responsible for repeat instability. In addition, we are optimizing the use of zinc-finger nucleases that introduce double-strand breaks into CAG repeats, and zinc-finger nickases that introduce single strand breaks, as reagents to shrink long CAG tracts as a potential therapy for human patients.
Targeted Genome Modification
Retinitis pigmentosa (RP), which affects 1 in every 3000 people worldwide, typically begins with loss of peripheral vision in the teens and progresses to tunnel vision and blindness in middle age. We are developing gene-specific strategies for genome modification, with the ultimate aim of treating this disease in humans. Dominant mutations in the rhodopsin gene are the largest single cause of RP.
To develop treatment protocols, we have generated mouse models in which one copy of the mouse rhodopsin gene is replaced with one or another forms of the human rhodopsin gene fused to GFP. These fluorescently tagged mouse models provide convenient color markers for the assessment of treatment efficacy. We are using these mouse models to test and optimize various gene specific cleavage reagents such as zinc-finger nucleases for their ability to correct or knockout defective genes. These studies will also elucidate the DNA repair capabilities of terminally differentiated neurons, which are currently undefined.
Websites
Selected Publications
-
Lin Y, Leng M, Wan M, Wilson JH. " Convergent Transcription through a Long CAG Tract Destabilizes Repeats and Induces Apoptosis. " Mol. Cell. Biol.. 2010 Sep ; 30 (18) : 4435-51.
Pubmed PMID: 20647539. -
Mansergh FC, Vawda R, Millington-Ward S, Kenna PF, Haas J, Gallagher C, Wilson JH, Humphries P, Ader M, Farrar GJ. " Loss of photoreceptor potential from retinal progenitor cell cultures, despite improvements in survival. " Exp. Eye Res.. 2010 Oct ; 91 (4) : 500-12.
Pubmed PMID: 20637750. -
Hubert L, Lin Y, Dion V, Wilson JH. " Topoisomerase 1 and Single-Strand Break Repair Modulate Transcription-Induced CAG Repeat Contraction in Human Cells. " Mol. Cell. Biol.. 2011 Aug ; 31 (15) : 3105-12.
Pubmed PMID: 21628532. -
Chan F, Hauswirth WW, Wensel TG, Wilson JH. " Efficient mutagenesis of the rhodopsin gene in rod photoreceptor neurons in mice. " Nucleic Acids Res.. 2011 Aug 1; 39 (14) : 5955-66.
Pubmed PMID: 21478169.
Memberships
- Association for Research in Vision and Ophthalmology
- Member (01/2001)
- American Society for Biochemistry and Molecular Biology
- Member (01/1986)
- Federation of American Societies for Experimental Biology
- Member (01/1975)
- American Association for the Advancement of Science
- Member (01/1975)
- American Society of Microbiology
- Member (01/1974)
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