PubMed search for Dr. Anthony W.S. Chan

Education:
1989 DVM National Taiwan University, Veterinary Medicine
1997 PhD University of Wisconsin-Madison, Endocrinology and Reproductive Physiology Program

Mission:
Our research interests are to develop an animal model that mimics patient conditions, which allows us to understand disease development, to develop early diagnostic tools and alternative therapeutic approaches such as cell and gene therapy.

Laboratory Research Interests:

Development of a transgenic nonhuman primate model of human inherited genetic disorders
Rodents have been the most popular animal models for inherited neurodegenerative disorders such as Huntington’s, Alzheimer’s, etc. However, due to their physiological and genetic differences from humans, the progression of disease is often difficult to interpret. Therefore, one of our missions is to develop a non-human primate model with a modified genetic background similar to that of a human patient to understand the disease and the development of efficacious medication. Because of the close genetic background and physiological resemblance with humans, monitoring disease development in non-human primates will provide invaluable information for accurate justification of novel medications, therapeutic procedures and the understanding of the diseases. We are currently developing a nonhuman primate model of Huntington’s and Alzheimer’s disease.

The biology and therapeutic applications of adult and embryonic stem cells
Embryonic stem (ES) cells hold great promise in treating diseases like Parkinson’s and other neurodegenerative diseases. However, differentiation control of ES cells is not yet clearly understood. Our goal is to establish a comparative model using rodent, non-human primate and human stem cells to understand the differentiation control, and we aim to identify the turning point of disease onset during development. We are also investigating the potential of therapeutic cloning and induced pluripotent stem cells as an alternative cell source using our transgenic monkeys as a model, which can then be used for evaluating their therapeutic potential. Our goal is to develop a non-human primate model to examine the potential of alternative approaches for deriving personal stem cells, thus the efficacy and safety of such a therapeutic scheme can be determined prior to clinical applications in humans. In addition to ES cells, adult stem cells are also being investigated as an alternative source in cell therapeutic study. Besides bone marrow mesenchymal stem cells (BMSCs), one of our interests is to investigate the potential of dental pulp stem cells (DPSCs) as an alterative cell source for personal cell therapy.

Assisted reproductive techniques (ART) and cell fate determination in mouse and nonhuman primate models
The entry of the sperm in the oocyte during fertilization plays an important role in determining cell fate and embryonic patterning. We are interested in investigating the role of sperm in embryos fertilized by different methods such as natural fertilization, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). IVF and ICSI are commonly used in fertility clinics; however, their profound effect on embryonic patterning, genetic, and epigenetic configuration has not been fully investigated. Our goal is to investigate the role of sperm in early embryonic development and its potential role in the decision of differentiation commitment.

Development of a noninvasive imaging reporter
Cell replacement therapy holds the greatest promise for treating neurodegenerative diseases such as Parkinson’s and Huntington’s, which is supported by encouraging results from both clinical and basic science studies. Despite the rapid advances in research on embryonic or adult stem cells, and increasing evidence of positive outcomes, clinical translations with stem cells have been limited. One major hurdle for the clinical application of cell replacement therapies is the risk of tumorigenesis and immuno-rejection. One major limitation is the ability to monitor cell grafts in vivo, thus the evaluation of therapeutic functions and conditions of cell grafts cannot be closely correlated to the clinical symptoms. Even in animal studies, the status of cell grafting cannot be evaluated until the animals are sacrificed for histologic examination. Our goal is to develop a transgenic MRI reporter, thus non-invasive and long term imaging could be performed in animal models for the evaluation of cell therapeutic efficacy and the spatial-temporal distribution of the cell graft without the use of invasive procedures.

Chan's Team:

Previous Lab Members:

Post-doctoral fellows:
Wu, Ming-Yih (National Taiwan University)
Meng, Qinggang (Utah State University)
Huang, Anderson Hsien-Cheng (Grace Dental Clinics, Taiwan)

Graduate students:
Chanchao, Lorthongpanich (Suranaree University of Technology)

Selected Representative Publications:

Shang-Hsun Yang, Pei-Hsun Cheng, Heather Banta, Karolina Piotrowska-Nitsche, Jin-Jing Yang, Eric C.H. Cheng, Brooke Snyder, Jun Liu, Katherine Larkin, Jack Orkin, Zhihui Fang, Yoland Smith, Jocelyne Bachevalier, Stuart M. Zola, Shihua Li, Xiao-Jiang Li and Anthony WS Chan (2008) Toward a Transgenic Model of Huntington’s Disease in the Nonhuman Primate. Nature (In Press)

Pei-Hsun Cheng, Brooke Snyder, Dimitri Fillos, Chris C. Ibegbu, Anderson Hsien-Cheng Huang, and Anthony W.S. Chan (2008) Postnatal Stem/Progenitor Cells Derived from the Dental Pulp of Adult Chimpanzee. BMC Cell Biology (In Press)

Cansu Agca, Stephanie Carter, Jason J. Fritz, Lary C. Walker, Allan I. Levey, Anthony WS Chan*, James J. Lah, and Yuksel Agca (2008) Development of Transgenic Rats Producing Human β-Amyloid Precursor Protein as a Model for Alzheimer’s Disease; Transgene and internal APP genes are regulated tissue-specifically. BMC Neuroscience (9) 28 *Co-correspondence

Chanchao Lorthongpanich, Shang-Hsun Yang, Karolina Piotrowska-Nitsche, Rangsun Parnpai and Anthony WS Chan (2008) Development of single mouse blastomeres into blastocysts, outgrowths and the establishment of embryonic stem cells. Reproduction (In Press)

Omar Zurkiya, Anthony W.S. Chan*, Xiaoping Hu*. (2008) MagA is sufficient for producing magnetosomes in mammalian cells in vivo making it an MRI reporter. Magnetic Resonance Medicine (In Press). *These authors contributed equally to this work and are co-correspondence.

Shang-Hsun Yang, Yuksel Agca, Pei-Hsun Cheng, Jin-Jing Yang , Cansu Agca, and Anthony Wing Sang Chan, (2007) Enhanced Transgenesis by Intracytoplasmic Injection of Envelope-free Lentivirus. Genesis (45):177-183

Chan, A.W.S., K.Y. Chong, C. Martinovich, C. Simerly, and G. Schatten. (2001). Transgenic monkeys produced by retroviral gene transfer into mature oocytes. Science 291:309-312.

Chan, A.W.S., T. Dominko, C.M. Luetjens, E, Neuber, C. Martinovich, L. Hewitson, C. Simerly, and G. Schatten. (2000). Clonal propagation of primate offspring by embryo splitting. Science 287:317-319.