Amy Wong

Amy Wong PhD
Assistant Professor
Department of Laboratory Medicine & Pathobiology
Amy Wong
Contact Info
T: (416) 813-7654 309426
Website
Location
Hospital for Sick Children (SickKids)
Hospital for Sick Children Research Institute - Prog of Dev & Stem Cell Bio
686 Bay St., Rm 17-9704
Toronto, ON, M5G 0A4
Appointment Status Primary
Research Interests
Molecular & Cell Biology, Human Development & Aging

I am a Scientist in the Program of Developmental & Stem Cell Biology at the Hospital for Sick Children. I completed my PhD in Toronto in thoracic surgery and regenerative medicine with Dr. Tom Waddell (University Health Network), and my post-doctoral training at the Hospital for Sick Children with Dr. James Ellis and Dr. Janet Rossant, where my research was focused on iPSC reprogramming and airway epithelial differentiation.

I was one of the first to develop a method to differentiate human pluripotent stem cells into lung epithelia modeling lung developmental pathways (Nature Biotech 2012 and Nature Protocol 2015) and use these cells to model Cystic fibrosis disease. This pioneering work showed that human induced pluripotent stem (iPS) cell-derived airway epithelia can potentially be used in personalized precision medicine. Recently, I have developed a direct cell reprogramming strategy to generate lung-like progenitor cells directly from fibroblasts (NPJ Scientific Reports 2019). These induced lung-like epithelial cells (iLEP) may serve as an alternative cell source for tissue regeneration.

Now, my lab is using the stem cell models I have developed to understand human lung development, lung disease and therapies.

Research/Teaching

Research Synopsis

Human lung development is largely unknown and what is known has been interpreted from loss-of-function mouse models.  my research program goal is to advance our understanding of the molecular and cellular processes that drive human lung development and disease, leading to improved derivation of lung tissue from pluripotent stem cells, and translating into novel stem cell-derived therapies for lung diseases.

Research program goal

To advance our understanding of the molecular and cellular processes that guide human lung development and disease, leading to improved derivation of lung tissue from pluripotent stem cells, and translating into novel stem cell-derived therapies for lung diseases.

The adult lung consists of more than 60 cell types organized in a complex branching system with multiple functions, including gas exchange, detoxification and immune surveillance. These functions are regulated by the cells that reside in the different regions of the lungs, from the multi-epithelial cell lineages forming the pseudostratified epithelium of the proximal airway to the thin monolayer of alveolar cells of the respiratory epithelium. How the lung arises from a sheet of embryonic endoderm and give rise to such an intricate organ with all the different cell types in the adult lung remains largely unknown. With improving single cell technologies, new cell types are being discovered, but the origins of these cells, their relationship with known cell types and their functions during development, disease and repair have yet to be determined.

Furthermore, human lung development remains largely unknown because embryonic and prenatal lung tissues are not easily accessible. Present knowledge of the genes and regulatory pathways that control lung development derives mostly from loss-of-function mouse models. However, the details of mouse lung development may not capture human processes, because mouse and human have distinct genetics, phenotypes, and lung structures. One way to circumvent mouse and human lung differences is to use human induced pluripotent stem (iPS) cells to model human development. I developed novel human models of lung derived from embryonic stem (ES) and iPS cells. My research program will use these models to discover the fundamental genetic and molecular processes that dictate how the human lung develops, how disease mutations such as CF affect lung development and progressive lung disease, and novel cell-based develop tools for personalized medicine.

Cystic Fibrosis (CF) is a genetic disorder affecting 1/2500 live births in Canada. While it is a multi-organ disease the main cause of morbity and mortality is due to the disease in the lungs. Mutation in the CF Transmembrane Conductance Regulator (CFTR) gene was identified as the primary genetic cause of CF. The CFTR protein is localized to the apical epithelial membrane and functions to transport ions and fluids across the epithelia. The loss of CFTR channel function or presence caused by disease mutations leads to mucus obstruction in the airways increasing the susceptibility to recurrent bacterial infections and chronic inflammation that ultimately destroys the lungs.

During lung development, CFTR has been implicated in mechanicosensory, lung morphogenesis and progenitor cell function however a direct link has not been shown. In utero gene transfer of anti-sense CFTR mRNA prevent lung development and cell differentiation in mouse lungs. Meanwhile over expression of CFTR in utero increases bronchial cell differentiation and proliferation at the expense of alveolar development.4 These studies implicate the role of CFTR in early lung development that may ultimately affect progressive lung deterioration and clinical responses to therapies.

My lab will define a deeper understanding of the progression of early human lung development from a pluripotent stem cell to the formation of mature lung using human stem cell-derived models that I have developed along with parallel animal models. These studies will shed critical insight into the genetic and molecular causes of lung diseases such as CF and ultimately translate into improved derivation of human lung tissues for modeling and novel stem cell-based therapies for lung diseases.

My research program will provide a comprehensive understanding of how specialized human lung epithelial cells are developed and contribute to diseases. This will inform strategies to generate novel relevant models to study personalized human lung diseases in a dish and therapy discoveries. My research program will provide an exciting interdisciplinary training environment, produce high-impact papers and lead to future clinical translation directly in lung disease.

Publications and Awards

View PubMed search of this faculty member's recent publications.

Recent Publications

Wong AP, Sharareh Shojaie, Claudia Bilodeau, Qin Liang, Michelle Di Paola, Pascal Duchesneau, Saumel Ahmadi, Sunny Xia, Jodi Garner, Martin Post, Tom Waddell, Christine Bear, Andras Nagy, Janet Rossant. Direct lineage reprogramming of human and mouse fibroblasts into epithelial progenitors capable of generating airway epithelia. Sci Rep. 2019 Jun 21;9(1):9027.

Eckford PW, McCormack J, Munsie L, He G, Stanojevic S, Pereira S, Ho K, Avolio J, Bartlett C, Yang JY, Wong AP, Wellhauser L, Huan LJ, Jiang J, Ouyang H, Du K, Klingel M, Kyriakopoulou L, Gonska T, Moraes TJ, Strug LJ, Rossant J, Ratjen F, Bear CE. The CF Canada-Sick Kids Program in Individual CF Therapy: A Resource for the Advancement of Personalized Medicine in CF. Journal of Cystic Fibrosis 2018 Apr 20 S1569-1993(18)30086-9.

Ahmadi S, Bozoky Z, Di Paola M, Xia S, Li C, Wong AP, Wellhauser L, Molinski S, Ip W, Ouyang H, Avolio J, Forman-Kay JD, Ratjen F, Hirota JA, Rommens J, Rossant J, Gonska T, Moraes TJ, Bear CE. Phenotypic profiling of CFTR modulators in patient-derived respiratory epithelia. NPJ Genom Med. 2017 Apr 14;2:12.

Wong AP, Stephanie Chin, Sunny Xia, Jodi Garner, Christine Bear, Janet Rossant. Efficient generation of functional CFTR-expressing airway epithelial cells from human pluripotent stem cells. Nature Protocols. 2015 Mar;10(3):363-81

Wong AP, Bear C, Chin S, Pasceri P, Thompson T, Huan LJ, Ratjen F, Ellis J, Rossant J.  Directed differentiation of human pluripotent stem cells into functional airway epithelial cells expressing CFTR protein. Nature Biotechnology, 2012 Sep;30(9):876-82.