AJaffeAron Jaffe, PhD
Chemical Biology & Therapeutics
Cambridge, Massachusetts, United States

Our current research is focused on understanding the signaling pathways that regulate epithelial morphogenesis, with the ultimate goal of identifying novel druggable nodes to promote tissue regeneration and repair. The generation, maintenance, and repair of epithelial tissues require the coordinated regulation of multiple cellular processes, such as cell polarity, cell-cell and cell-matrix interactions, and differentiation. We have established three-dimensional culture systems to model epithelial morphogenesis, and utilize these systems in a variety of screening and profiling modes to identify novel pathways regulating key cellular processes involved in morphogenesis. We are particularly interested in the mechanisms regulating epithelial progenitor cell fate decisions, because an imbalance in the differentiated cell types is observed in several pulmonary epithelial diseases, such as asthma and chronic obstructive pulmonary disease (COPD). We want to understand how epithelial progenitors choose to differentiate down a particular lineage, and how that decision is de-regulated in disease.

The work in my lab is currently directed towards addressing two key goals:

  1. Identification and characterization of the signaling pathways regulating airway basal cell fate decisions in normal and disease settings.
  2. Identifying the mechanisms regulating airway squamous metaplasia.

Selected Publications

Notch2 Is Required for Inflammatory Cytokine-Driven Goblet Cell Metaplasia in the Lung.
Danahay H, Pessotti AD, Coote J, Montgomery BE, Xia D, Wilson A, Yang H, Wang Z, Bevan L, Thomas C, Petit S, London A, LeMotte P, Doelemeyer A, Vélez-Reyes GL, Bernasconi P, Fryer CJ, Edwards M, Capodieci P, Chen A, Hild M, Jaffe AB.
Cell Rep. 2015; 10: 239-252.

TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation.
Mounir Z, Lin F, Lin VG, Korn JM, Yu Y, Valdez R, Aina OH, Buchwalter G, Jaffe AB, Korpal M, Zhu P, Brown M, Cardiff RD, Rocnik JL, Yang Y, Pagliarini R.
Oncogene. 2014; doi: 10.1038/onc.2014.308. [Epub ahead of print]

Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis.
Jaffe AB, Kaji N, Durgan J, Hall A.
J Cell Biol. 2008; 183: 625-33.

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