chandler-jensen-cody@uiowa.edu
Mentor: John Engelhardt, Ph.D.
Lab Room: 1-111 BSB
Lab Phone: 319-335-9613

Determining the Molecular Pathways that Dictate Submucosal Gland Stem Cell Function

The respiratory system of mammals is comprised of several distinct epithelial compartments, each with its own function and cellular composition. Submucosal glands (SMGs) are located in the proximal airways, embedded in the mesenchyme underneath the surface airway epithelium (SAE). Their main function is to synthesize and secrete mucous used to protect the airway from potential dangers brought in by inhaled air. Recently, however, SMGs have also been discovered to be a niche for resident epithelial stem cells. These stem cells are capable of regenerating epithelial cells of both the SMG and SAE, making them very intriguing therapeutic targets for diseases that affect the proximal airway, including cystic fibrosis, asthma, and chronic obstructive pulmonary disease (COPD).

Despite the interest in SMG stem cells, very little is actually known about their identity and physiology. Our goal in the Engelhardt lab is to discover what molecular pathways and proteins are necessary for SMG stem cell activation, migration, proliferation, and differentiation. My research hones in on the Wnt signaling pathway, as well as on the transcription factor Sox9. Wnt signaling is known to be active in SMGs, but Sox9 has only recently been discovered to have any function in the proximal airway. My overall goal is to determine what role Sox9 plays in enabling SMG stem cells to activate, and to determine the dynamic between Sox9 and Wnt signaling during SMG stem cell activation.

Lynch TJ, Anderson PJ, Rotti PG, Tyler SR, Crooke AK, Choi SH, Montoro DT, Silverman CL, Shahin W, Zhao R, Jensen-Cody CW, Adamcakova-Dodd A, Evans TIA, Xie W, Zhang Y, Mou H, Herring BP, Thorne PS, Rajagopal J, Yeaman C, Parekh KR, Engelhardt JF. Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium. Cell Stem Cell. 2018 May 3;22(5):653-667.e5. doi: 10.1016/j.stem.2018.03.017. Epub 2018 Apr 12. Erratum in: Cell Stem Cell. 2018 May 3;22(5):779. PubMed PMID: 29656941; PubMed Central PMCID: PMC5935589.

Rosen BH, Evans TIA, Moll SR, Gray JS, Liang B, Sun X, Zhang Y, Jensen-Cody CW, Swatek AM, Zhou W, He N, Rotti PG, Tyler SR, Keiser NW, Anderson PJ, Brooks L, Li Y, Pope RM, Rajput M, Hoffman EA, Wang K, Harris JK, Parekh KR, Gibson-Corley KN, Engelhardt JF. Infection Is Not Required for Mucoinflammatory Lung Disease in CFTR-Knockout Ferrets. Am J Respir Crit Care Med. 2018 May 15;197(10):1308-1318. doi: 10.1164/rccm.201708-1616OC. PubMed PMID: 29327941.

Yan Z, Feng Z, Sun X, Zhang Y, Zou W, Wang Z, Jensen-Cody C, Liang B, Park SY, Qiu J, Engelhardt JF. Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes. Hum Gene Ther. 2017 Aug;28(8):612-625. doi: 10.1089/hum.2017.060. Epub 2017 May 10. PubMed PMID:28490200; PubMed Central PMCID: PMC5567599.