Pediatrics

Research Overview

Fanconi anemia (FA) is an autosomal recessive disease that is characterized by congenital abnormalities, defective hematopoiesis, a high risk of developing acute myeloid leukemia and certain solid tumors, and cellular sensitivity to crosslinking agents. Human hemoglobinopathies, such as ß-thalassemia and sickle-cell disease, are the most prevalent of human monogenetic diseases and lead to severe anemia. Primary malignant liver tumors are the 10th most common pediatric malignancy. Adenosine deaminase deficiency leads to a devastating pediatric immune deficiency: severe combined immune deficiency (ADA-SCID).Since none of the currently used therapeutic approaches is curative, the development of a safe and effective gene therapy could achieve long-term benefits. Parvovirus vectors, including the non-pathogenic adeno-associated virus (AAV) and parvovirus B19 vectors have gained attention as a useful alternative to the more commonly used retrovirus- and adenovirus-based vectors in human gene therapy.

The goals of my research are to study molecular biology of human parvoviruses and their use as vectors in human gene therapy. My basic research efforts in this area are focused on developing new parvovirus vectors with high transduction efficiency and low immune response. I also focused on the research of hematopoietic stem cell gene therapy for beta-thalassemia, Fanconi anemia, leukemia and multiple myeloma as well as hepatocyte gene therapy for heptoblastoma, hepatocellular carcinoma and ADA-SCID. Publications, seminars, patent applications, and both extramural and intramural funding have reflected efforts to realize this goal. Funding over the past two years has been derivative of two National Institutes of Health grants (Co-investigator), one regular research grant from the Roche Foundation of Anemia Research (PI) and one intramural grant from Children's Miracle Network, Inc (PI).

About

Dr. Zhong is an Assistant Professor in the Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida. He received his MD degree from Hunan Medical University in China in 1994, and also received a Master's Degree in Medical Science in 1997 from the same institution. He also received his postdoctoral training in cellular and molecular biology, protein biochemistry, gene therapy and signal transduction research area at University of Washington School of Medicine in Seattle and Indiana University School of Medicine in Indianapolis.

Dr. Zhong have published more than 30 papers, mostly on human gene therapy, in peer reviewed journals such as Blood, Gene Ther., Hum. Gene Ther., J Biol. Chem., J Virol., Mol. Ther., PNAS and Virology, and presented more than 40 abstracts at local, national, and international meetings. Based on his research, a US patent application has been filed recently. His research was also awarded for oral presentation (Top abstract) at a special Plenary Session during the American Society of Gene Therapy 11th Annual Meeting, May 28-June 1, 2008, in Boston, MA

Key Publications

Additional publications can be found in PubMed.

1. Zhong L, Li B, Mah CS, Govindasamy L, Agbandje-McKenna M, Cooper M, Herzog RW, Zolotukhin I, Warrington KH Jr, Weigel-van Aken K, Hobbs, JA, Zolotukhin S, Muzyczka N, and Srivastava A. Next generation of recombinant adeno-associated virus 2 vectors: Point mutations in tyrosine lead to high-efficiency transduction at lower doses. Proc Natl Acad Sci USA 2008;105:7827-7832
2. Zhong L, Zhou X, Li Y, Qing K, Xiao X, Samulski RJ and Srivastava A. Single-polarity recombinant AAV2- mediated transgene expression in vitro and in vivo: Mechanism of transduction. Mol Ther 2008;16:290-295
3. Zhong L, Zhao W, Wu J, Li B, Zolotukhin S, Govindasamy L, Agbandje-McKenna M and Srivastava A. A dual role of epidermal growth factor receptor protein tyrosine kinase signaling in ubiquitination of AAV2 capsids and viral second-strand DNA synthesis. Mol Ther 2007; 15:1323-1330
4. Zhong L, Li W, Li Y, Zhao W, Wu J, Li B, Maina N, Bischof D, Qing K, Weigel-Kelley K, Zolotukhin I, Warrington K, Li X, Slayton W, Yoder M and Srivastava A. Evaluation of primitive murine hematopoietic stem and progenitor cell transduction in vitro and in vivo by recombinant adeno-associated virus vector serotypes 1 through 5. Hum Gene Ther 2006;17:321-333
5. Zhong L, Li W, Yang Z, Qing K, Tan M, Hansen J, Li Y, Chen L, Chan RJ, Bischof D, Maina N, Weigel-Kelley KA, Zhao W, Larsen SH, Yoder MC, Shou W and Srivastava A. Nuclear transport and virus uncoating limit recombinant adeno-associated virus type 2 vectors-mediated transduction of primary murine hematopoietic cells. Hum Gene Ther 2004; 15: 1207-1218.