John H Wilson, Ph.D.

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John H Wilson, Ph.D.

Distinguished Service Professor

Email

jwilson@bcm.edu

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.