Email

png@bcm.edu

Positions

Associate Professor

Molecular and Human Genetics
Baylor College of Medicine
Houston, TX US

Associate Professor

Program in Translational Biology & Molecular Medicine
Baylor College of Medicine

Education

BS from University Of Toronto

01/1990 - Toronto, Canada

MS from University Of Guelph

01/1994 - Guelph, Canada

PhD from University Of Guelph

01/1999 - Guelph, Canada

Post-Doctoral Fellowship at McMaster University

01/2001 - Hamilton, Ontario Canada

Professional Interests

• Liver and lung gene therapy

Professional Statement

My laboratory is interested in developing gene therapies using helper-dependent adenoviral vectors (HDAd). HDAd (also called gutless or gutted adenovirus) does not contain any viral genes and thus represents a major improvement over early generation adenoviral vectors with respect to safety and efficacy. These vectors can transduce target cells with high efficiency to provide high-level long-term transgene expression without chronic toxicity. Studies into improving the production of HDAd as well as their characterization are ongoing in my laboratory including manufacturing the vector under current Good Manufacturing Practices (cGMP) for clinical applications in humans.

A focus of my laboratory is liver-directed gene therapy using HDAd to treat a wide variety of genetic and acquired diseases such as hemophilia, Crigler-Najjar syndrome, cardiovascular disease, alpha 1-antitrypsin deficiency and many others. We are investigating novel methods of delivering HDAd preferentially into the liver of mice, dogs and nonhuman primates. We have developed a minimally invasive, balloon occlusion catheter-based method to deliver HDAd preferentially into the liver of large animals which results in negligible toxicity and long-term, high-level transgene expression. This technology may pave the way towards human clinical application for a wide variety of genetic and acquired diseases. We are also investigating ways of modifying the capsid of the vector to achieve preferential transduction of hepatocytes.

Another major focus of my laboratory is lung-directed gene therapy using HDAd with the primary goal of treating cystic fibrosis. We have developed a novel method of aerosolizing HDAd into the lungs of nonhuman primates which has resulted in very high-efficiency gene transfer to the airway epithelium with negligible toxicity. These encouraging and compelling results may pave the way to treat patients with cystic fibrosis in the future.

We are also interested in investigating the innate and adaptive immune responses to HDAd. These important studies will provide information regarding the host-vector interactions which will be very useful for further improving the safety and efficacy of HDAd-mediated gene therapy.

Another active area of research in my lab is gene editing of human-induced pluripotent stem cells (iPSCs) by HDAds. Gene editing of iPSCs has emerged as a powerful tool in research and has great potential in medicine. The major appeal of HDAd-mediated gene editing is that induction of an artificial double-stranded break at the chromosomal target locus by a designer endonuclease is not required to achieve high targeting efficiency, thereby eliminating the potential for off-target cleavage. We are interested in understanding the mechanism of gene editing by HDAd so that we may further improve its efficiency to ultimately permit direct and efficient in vivo gene editing in the future.

Selected Publications

• Palmer DJ, Grove NC, Ng P "Helper virus-mediated downregulation of transgene expression permits production of recalcitrant helper-dependent adenoviral vector.." Mol Ther Methods Clin Dev.. 2016;3:16039.
• Palmer DJ, Grove NC, Ing J, Crane AM, Venken K, Davis BR, Ng P "Homology requirements for efficient, footprintless gene editing at the CFTR locus in human iPSCs with helper-dependent adenoviral vectors.." Mol Ther Nucleic Acids.. 2016;5:e372.
• Brunetti-Pierri N, Ng T, Iannitti D, Cioffi W, Stapleton G, Law M, Breinholt J, Palmer D, Grove N, Rice K, Bauer C, Finegold M, Beaudet A, Mullins C, Ng P "Transgene Expression up to 7 Years in Nonhuman Primates Following Hepatic Transduction with Helper-Dependent Adenoviral Vectors.." Hum Gene Ther.. 2013;24(8):761-5. Pubmed PMID: 23902403
• Brunetti-Pierri N, Liou A, Patel P, Palmer D, Grove N, Finegold M, Piccolo P, Donnachie E, Rice K, Beaudet A, Mullins C, Ng P "Balloon Catheter Delivery of Helper-dependent Adenoviral Vector Results in Sustained, Therapeutic hFIX Expression in Rhesus Macaques.." Mol. Ther.. 2012 Oct;20(10):1863-70. Pubmed PMID: 22828499