Department of Biomedical Sciences
Member of the GSBS Faculty
3302 Gaston Ave.
Sciences Bldg., Room 235A
Dallas, Texas 75246
Education and Post-Graduate Training
Postdoctoral Fellowship, Embryology and Genetics (2005); Bioinformatics and Toxicology (2006), University of Louisville, Louisville, KY
Ph.D., Molecular and Cellular Biology (Experimental Medicine), McGill University, Montreal, Canada (2002)
B.Sc., Biology/Microbiology, University of Sherbrooke, Sherbrooke, Canada (1996)
Associate Professor, Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX (2016 - present)
Assistant Professor, Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX (2006-2016)
Research Associate, University of Louisville School of Dentistry (2004-2006)
Postdoctoral Research Associate, University of Louisville School of Dentistry (2002-2004)
Teaching responsibilities include:
Physiology (dental); Growth and Mechanisms of Development; Advanced Human Craniofacial Development and Craniofacial Anomalies (graduate)
One in 33 children is born with birth defects. Cardiovascular malformations, the most common defects, affect about one in 110 children while craniofacial defects affect one in 700 children. These facts are the driving forces motivating me to do this research. I want to elucidate the mechanisms by which these defects arise.
Several of these malformations arise in structures derived from neural crest cells. Neural crest cells (NCC) are a distinct cell population that delaminate from the neural fold and migrate ventrally in the embryo, giving rise to various anatomical structures. Cephalic NCCs migrate into the first, second, third and fourth pharyngeal arches to form most of the craniofacial skeleton and cranial ganglions. Cardiac NCCs migrate into pharyngeal arches 3, 4 and 6 where they participate in the asymmetric remodeling of the pharyngeal arch arteries into the great vessels and form the vascular smooth muscles of the great vessels. A subpopulation of cardiac NCCs also migrates into the cardiac outflow tract, where they contribute to the outflow tract septation into the pulmonary and aortic outflows.
The main goal of my research program is to understand how improper regulation of NCC development leads to a variety of birth defects. Accordingly, my program seeks to understand how NCCs are formed, what initiates the expression of NCC-specific genes, what regulates their migration and final destination and how they differentiate into proper structures by activating specific genes and finally establish structural identity. To achieve these goals and understand the events leading to birth defects, we use different genetic, molecular and cellular biology tools to study craniofacial and cardiovascular development during mouse embryogenesis with emphasis on the endothelin system.
One or several signaling pathways crucial for NCC development are regulated by the endothelin-A receptor (Ednra)/endothelin 1 (Edn1) system. During embryonic development, Ednra is expressed in cephalic and cardiac NCCs while its ligand Edn1 is expressed in the pharyngeal arch ectoderm, core paraxial mesoderm and pharyngeal pouch endoderm. Targeted deletion of the genes encoding Ednra or Edn1 in the mouse causes severe craniofacial and cardiovascular defects of NCC-derived structures, resulting in early postnatal lethality.
My research program currently focuses mainly on four aims:
1. Identify and investigate the role of the downstream effectors of Ednra signaling during craniofacial and cardiovascular development.
2. Investigate the role of Ednra signaling in establishing a mandibular identity in the NCCs.
3. Investigate how Ednra expression is regulated in cephalic and cardiac neural crest cells.
4. Investigate the genetic events regulating upper jaw patterning.
- Endothelin-A Receptor Function in Cardiovascular Development. American Heart Association; $140,000 (2011-2012)
- Identification of the Elements Regulating Ednra Expression in Neural Crest Cells; Research Development Grant, Office of the VP for Research and Graduate Studies, Texas A&M Health Science Center; $15,000 (2007-2012)
- Leica SP5 Confocal Microscope, Equipment grant. National Institutes of Health; Co-I; 2010-2011
Ruest LB, Marcotte R, Wang E (2002). Peptide elongation factor eEF1A-2/S1 expression in cultured differentiated myotubes and its protective effect against caspase-3-mediated apoptosis. J. Biol. Chem. 277: 5418-5425.
Ruest LB, Khalyfa A, Wang E (2002). Development-dependent disappearance of caspase-3 in skeletal muscle is post-transcriptionally regulated. J. Cell. Biochem. 86: 21-28.
Ruest LB, Dager M, Yanagisawa H, Charite J, Hammer RE, Olson EN, Yanagisawa M, Clouthier DE (2003). dHAND-Cre transgenic mice reveal specific potential functions of dHAND during craniofacial development. Dev. Biol. 257: 263-277.
Ruest LB, Hammer RE, Yanagisawa M, Clouthier DE (2003). Dlx5/6-enhancer directed expression of Cre recombinase in the pharyngeal arches and brain. Genesis 37: 188-194.
Pan J, Ruest LB, Xu S, Wang E (2004). Immuno-characterization of the switch of peptide elongation factors eEF1A1/EF-1α and eEF1A-2/S1 in the central nervous system during mouse development. Dev. Brain Res. 149:1-8.
Ruest LB, Xiang X, Lim KC, Levi G, Clouthier DE (2004). Endothelin-A receptor-dependent and independent signaling pathways in establishing mandibular identity. Development 131: 4413-4423.
Ruest LB, Kedzierski R, Yanagisawa M, Clouthier DE (2005). Deletion of the endothelin-A receptor gene within the developing mandible. Cell Tissue Res. 319: 447-453.
Abe M, Ruest LB, Clouthier DE (2007). Fate of neural crest cells during craniofacial development in endothelin-A receptor-deficient mice. Int. J. Dev. Biol. 57:97-105.
Datta S, Turner D, Singh R, Ruest LB, Pierce WM Jr., Knudsen TB (2008). Fetal Alcohol Syndrome (FAS) in C57 BL/6 mice detected through proteomics screening of the amniotic fluid. Birth Defects Res (Part A Clin. Mol. Teratol.) 82:177-186.
Ruest LB, Clouthier DE (2009). Elucidating timing and function of endothelin-A receptor signaling during craniofacial development using neural crest cell-specific gene deletion and receptor antagonism. Dev. Biol. 328:94-108.
Yu W, Ruest LB, Svoboda KK (2009). Regulation of epithelial-mesenchymal transition in palatal fusion. Exp. Biol. Med. (Maywood) 234:483-491.
Yu W, Serrano M, Miguel SS, Ruest LB, Svoboda KK (2009). Cleft lip and palate genetics and application in early embryological development. Indian J. Plast. Surg. 42 Suppl:S35-50.
D'Souza R, Ruest LB, Hinton R, Svoboda K (2010). Development of the craniofacial complex. Topics in Bone Biology: Bone and Development (Vol. 6, Chapter 10), Bronner F, Farach-Carson MC and Roach HI, eds., Springer, pp. 153-181.
Green M, Singh A, Ruest LB, Pisano M, Prough R, Knudsen T (2011). Differential programming of p53-deficient embryonic cells during rotenone block. Toxicology 290:31-41.
Zhang Y, Blackwell EL, McKnight MT, Knutsen GR, Vu WT, Ruest LB (2012). Specific inactivation of Twist1 in the mandibular arch neural crest cells affects the development of the ramus and reveals interactions with Hand2. Dev. Dyn. 241:924-940.
Zhang Y, Ruest LB (2012). Analysis of neural crest cell fate during cardiovascular development using Cre-activated lacZ/β-galactosidase staining. Methods Mol. Biol. 843:125-138.
- Gibson MP, Zhu Q, Wang S, Liu Q, Liu Y, Wang X, Yuan B, Ruest LB, Feng JQ, D'Souza RN, Qin C, Lu Y (2013). The rescue of dentin matrix protein 1 (DMP1)-deficient tooth defects by the transgenic expression of dentin sialophosphoprotein (DSPP) indicates that DSPP is a downstream effector molecule of DMP1 in dentinogenesis. J. Biol. Chem. 288:7204-14.
- Yu W, Zhang Y, Ruest LB, Svoboda KK. Analysis of Snail1 function and regulation by Twist1 in palatal fusion. Front. Physiol. [Epub 2013 Feb 19]
- Zhang Y, Knutsen GR, Brown MD, Ruest LB (2013). Control of endothelin-a receptor expression by progesterone is enhanced by synergy with Gata2. Mol. Endocrinol. 27:892-908.
|2002-2004||Research Fellowship, Heart and Stroke Foundation of Canada|
|1998-2001||Doctoral Research Award, Canadian Institutes of Health Research|
|1995||Summer Student Scholarship, Fond de Recherche en Santé du Québec|
|1994||Scholarship, Foundation Desjardins (Canada)|