Research

For 10 years we have worked together with Drs. Andrew Wilson and Darrell Kotton as the “KIWi” group, merging our finances, facilities, and group meetings to accomplish our shared mission of regenerating lung and other endodermal lineages. You can find more information on the KIWi group here

trachea and thyroid-merged with BF-E13.5

Lung & Thyroid Progenitor Biology
A longstanding interest of our lab is understanding the biology of lung and thyroid primordial progenitors, i.e. the initial cells to adopt a lung or thyroid fate within the foregut endoderm. We have been using both in vivo (mouse) and in vitro iPSC/ESC-based systems to gain a mechanistic understanding of the progenitor specification and early patterning. We are currently delving into the questions of progenitor heterogeneity and bistability in cell fate decisions and their functional implications for the development of efficient and robust directed differentiation protocols. We take a truly multidisciplinary approach to these studies by collaborating with developmental biologists (Bob Varelas, Biochemistry), scientist-clinicians (Darrell Kotton, CReM), bioengineers (Wilson Wong, BME), physicists (Pankaj Mehta, Physics) and bioinformaticians (Paul Blainey, Broad Institute).

2 NIS(r) TG(g) DNA(b).jpg

 

Biomechanical Determinants of Lung & Thyroid Development
Another area of interest is the role of biomechanical determinants such as elastic modulus and extracellular matrix composition on lung and thyroid cell specification and differentiation. To tackle this problem, we employ a variety of approaches such as measurement of the biomechanical properties of the developing lung, use of medium throughput screens for discovery of appropriate biomechanical cues and 3D bioprinting for the manufacturing of lung/thyroid tissue-like constructs. There are ongoing collaborations in this area with Joyce Wong and Bela Suki (BME), Gustavo Mostoslavsky (CReM) and Bob Varelas (Biochemistry).

 

Nanog-GFP iPSCs in Aggrewell platesBioprocessing of Endodermal Lineages
An area under development is the use of benchtop bioreactors for the transition to suspension culture of the KIWi group directed differentiation protocols. As the derivation of clinically relevant cell types, such as thyrocytes and Type II alveolar epithelial cells, is becoming more efficient, potential applications such as PSC-based disease modeling and high throughput screening of small molecule effectors of differentiation are within reach. Therefore, we plan to develop bioprocessing approaches that will provide the large quantities of functional cells needed for these applications.