Conway Lab

The research laboratory of Simon Conway, PhD, is focused on examination and manipulation of the molecular regulatory mechanisms that govern cardiopulmonary development and disease. The lab specializes in using transgenic mouse modeling approaches to understand pathogenesis. With these models, the Conway Lab seeks to identify the mechanisms and cell lineages responsible for disease development and transgenically and/or pharmacologically correct the various structural and functional defects.

Active Research

Over the last 19 years, the Conway Lab has primarily focused on the pathogenesis of transcription factors Pax3/7 and the transforming growth factor-beta (TGFβ) superfamily mediated cardiac neural crest (NC)-associated congenital conotruncal heart defects.

Conotruncal heart defects (CHDs) result from a failure of the aorta and pulmonary trunks of the outflow tract (OFT) to become separate blood vessels. These defects are frequently associated with endocardial cushion/valve anomalies, and mutant mice exhibiting these CHDs often exhibit bradycardia and die in utero. Furthermore, lack of NC-mediated OFT septation often results in respiratory failure and abnormal lung maturation. Through the use of both physiological hyperoxia and transgenic approaches, the lab is testing whether initial suppression of the TGFβ signaling apparatus, as well as loss of key downstream TGFβ superfamily effectors, underlie lung malformations.

Recently, the lab has become interested in the cardiopulmonary roles of the TGFβ-responsive Periostin and TGFBI matricellular proteins. Significantly, the lab has shown that a partial Periostin element is uniquely capable of driving reporter expression in activated cardiac myofibroblasts, providing a unique in vivo tool for genetic manipulation of activated injury-site fibroblasts. Additionally, the lab generated Periostin and TGFBI knockout mice to test their functional requirement in heart and lung maturation, their responses to injury and their roles during multi-organ homeostasis and fibrosis.

Studies conducted in the Conway Lab contribute significantly to the current understanding of cardiopulmonary defect pathogenesis and seek to use basic research to uncover novel therapeutic approaches for the diagnosis and mitigation of life-threatening diseases routinely seen in the clinic.

Research Funding

Molecular Mechanisms of Neural Crest-Related Congenital Heart Defects

Goals: To examine how Pax3 transcription factor regulates cardiac neural crest morphogenesis and determine the underlying mechanism of in utero heart failure in Pax3 nulls using systemic null, hypomorphic and lineage-restricted conditional mouse mutant models.

Mechanisms of adult cardiac and pulmonary fibrosis in relation to TGFβ signaling and miR-145 function.

Goals: Test whether microRNA miR145 regulates adult heart and lung fibrosis via regulation of downstream Periostin matricellular protein.

Mechanisms associated with systemic effects of cancer.

Goals: Test hypothesis that cancer-derived cytokine TNFα contributes to impairment of cardiac and muscle functions in part by suppressing systemic levels of miR-486.

Recent Publications

For a full list of Dr. Conway’s publications, find him on PubMed.

Kong P, Shinde AV, Su Y, Russo I, Chen B, Saxena A, Conway SJ, Graff JM, Frangogiannis NG. (2018). Opposing Actions of Fibroblast and Cardiomyocyte Smad3 Signaling in the Infarcted Myocardium. Circulation. 137:707-724. PMID:29229611

Alvarez M, Xu L, Himes E, Chitteti B, Childress P, Mohamad S, Olivos D, Cheng Y-H, Conway SJ, Srour EF, Kacena MA. (2018). Megakaryocyte and osteoblast interactions modulate bone mass and hematopoiesis. Stem Cells Dev. doi: 10.1089/scd.2017.0178. PMID:29631496

Duchamp de Lageneste O, Julien A, Abou-Khalil R, Frangi G, Carvalho C, Cagnard N, Cordier C, Conway SJ, Colnot C. (2018). Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin. Nat Commun. 9:773. doi: 10.1038/s41467-018-03124-z. PMID:29472541

Schwanekamp JA, Lorts A, Sargent M, York AJ, Gokey J, Whitsett JA, Conway SJ and Molkentin JD. (2017). TGFBI functions similar to Periostin but is uniquely dispensable during cardiac injury. PLOS One, 12:e0181945. PMID:28750100

Poulsen ET, Runager K, Nielsen N, Thomsen K, Snider P, Simmons O, Vorum H, Conway SJ* and Enghild JL*. (2017). Proteomic profiling of Tgfbi-null mouse corneas reveals only minor changes in matrix composition supportive of TGFBI knockdown as therapy against TGFBI-linked corneal dystrophies. FEBS, 285:101-114 [* joint corresponding authors]. PMID:29117645

Ahlfeld SK, Wang J, Gao Y, Snider P, Conway SJ. (2016). Initial suppression of TGFβ signaling and loss of TGFBI causes early alveolar structural defects resulting in bronchopulmonary dysplasia. Am J Pathol. 186:777-93. PMID:26878215

Zhou HM and Conway SJ. (2016). Restricted Pax3 deletion in the neural tube results in congenital hydrocephalus. J. Dev. Biol. 4(1), 7; doi:10.3390/jdb4010007. PMCID:PMC4777317

Simmons O, Snider P, Wang J, Schwartz RJ, Chen YP and Conway SJ. (2015). Persistent Noggin arrests cardiomyocyte morphogenesis and results in early in utero lethality. Dev. Dyn. 244:457-67. PMID:25428115

Lajiness JD, Snider P, Wang P, Feng GS, Krenz M and Conway SJ. (2014). Shp2 deletion in post-migratory neural crest cells results in impaired cardiac sympathetic innervation. Proc Natl Acad Sci USA., 111:E1374-82. PMID:2470681

Faculty Research Team

Simon J. Conway, PhD

Simon J. Conway, PhD

Professor of Pediatrics
Paige L. Snider, PhD

Paige L. Snider, PhD

Assistant Research Professor of Pediatrics
Olga I. Simmons, MS

Olga I. Simmons, MS

Research Associate in Pediatrics
Wenjun Zhang, PhD

Wenjun Zhang, PhD

Visiting Assistant Research Professor of Surgery