Dr. Brian R. Davis
The University of Texas Health Science Center at Houston
Institute of Molecular Medicine
Center for Stem Cell Research
- Gene editing of stem cells
- Stem cell biology
- Gene therapy
- Hematopoietic stem cells
- Somatic reversion
- Molecular genetics
The research in my laboratory is focused on gene editing in stem cells, that is utilizing homologous recombination and/or DNA repair processes to restore an endogenous mutant gene sequence to the corrected normal sequence in autologous stem cells obtained from patients with inherited genetic disease. Alternately, gene editing could be used to introduce specific changes (e.g. SNPs) into genes in normal stem cells for a functional evaluation of such changes. One line of investigation has been to develop novel gene therapeutics using Zinc Finger Nuclease (ZFN) facilitated gene editing to correct gene mutations or target integration of transgenes into specific chromosomal sites directly in hematopoietic stem/ progenitor or mesenchymal stem cells. Such corrected stem cells would be transplanted back into patients with inherited genetic diseases such as primary immunodeficiencies (e.g. X-linked SCID, Wiskott-Aldrich Syndrome) or muscular dystrophies. We hypothesize that direct correction of mutations or targeted transgene integration at the endogenous chromosomal location, under native gene transcriptional control, should result in more physiologic correction of defects than that achievable through random gene addition approaches. A second line of investigation is focused on spontaneous somatic reversion of inherited mutations or “natural gene therapy” in patients with inherited genetic disease. This project has developed out of our identification of numerous genetic revertants in a patient with Wiskott-Aldrich Syndrome. This provides an unprecedented snapshot of natural selection at work within a patient with an inherited genetic disease – acting upon a repertoire of mutant genotypes to select those encoding protein(s) with greatest functionality.
A tutorial in my laboratory would provide experience with various techniques in stem cell biology and gene modification technology. The laboratory makes extensive use of molecular biological techniques (e.g. DNA PCR, RT-PCR), cell isolation techniques (e.g. flow cytometric sorting, immunomagnetic positive and negative cell separation), and both viral and non-viral techniques of gene delivery. More importantly, a tutorial would provide intensive exposure to novel approaches to genetic modification of stem cells and their application to regenerative medicine.
BR Davis, NL Prokopishyn (2005) Stem Cell Gene Therapy. In Handbook of Stem Cells. Volume 2 (R. Lanza, ed.). Adult and Fetal Stem Cells. pp 793-804. Elsevier Academic Press.
BR Davis, NL Prokopishyn (2006) Stem Cell Gene Therapy. In Essentials of Stem Cell Biology (R. Lanza, ed.). pp 471-478. Elsevier Academic Press.
KK Goncz, NL Prokopishyn, A Abdolmohammadi, B Bedayat, R Maurisse, BR Davis, DC Gruenert (2006) SFHR-mediated modification of genomic beta-globin sequences in human hematopoietic stem/progenitor cells Oligonucleotides 16:213-224.
BR Davis, MJ DiCola, NL Prokopishyn, JB Rosenberg, D Moratto, LM Muul, F Candotti, RM Blaese (2007) Unprecedented diversity of genotypic revertants in lymphocytes of a patient with the Wiskott-Aldrich Syndrome, submitted.