Robert M. Greene, Ph.D.

Professor

Department of Surgical and Hospital Dentistry


Division of Craniofacial Development & Anomalies School of Dentistry Associate, Department of Pediatrics

Scholarly Activities

A quarter of a million babies—3% of all infants born in the US each year— have some mental or physical defect that is evident at birth. Since the causes of nearly all birth defects are largely unknown, research into molecular regulatory mechanisms responsible for normal embryogenesis provides the framework for investigations into the etiology of abnormal embryonic development.

Craniofacial malformations occur with a frequency of 1 in 600 live births annually in the United States.  Our previous studies have provided substantial evidence supporting the premise that various cellular signal transduction pathways interact to regulate cell proliferation and cell differentiation in embryonic craniofacial tissue. Such interactions represent the underpinnings of a complex and delicately balanced developmental system where morphogenesis and cellular differentiation of the craniofacial region are mediated by the sequential expression of molecular signals. Our studies dealing with molecular analyses of gene function in the embryo—utilizing the developing craniofacial region—are designed to provide definition and clarification of developmental signaling pathways critical for normal embryogenesis as well as identification of foci for perturbation and attendant fetal abnormalities.

Current studies—selected specifics outlined briefly below—are designed to identify means by which signal transduction pathways, known to be critical in development of the craniofacial region, regulate gene expression and embryonic development.

Overview of selected laboratory investigatory areas:

1 - microRNAs & epigenetic regulation of craniofacial development

2 - Transcriptional coactivators and craniofacial & neural tube development.

3 - Cigarette smoke-induced adverse developmental outcomes.

4 - TGFß/Smad signaling mechanisms in embryonic craniofacial development.


Peer-Reviewed Publications (2014-2017)

1 - Neal RE, Chen J, Jagadapillai R, Jang H, Abomoelak B, Brock GN, Brock G, Greene RM, Pisano MM. Developmental cigarette smoke exposure: hippocampus proteome and metabolome profiles in low birth weight pups. Toxicology 317:40-49 (2014) PMID: 24486158

2 - Warner DR, Greene RM, Pisano MM. PRDM16 in Development and Disease. Human Genetics & Embryology 4:1-4: http://dx.doi.org/10.4172/2161-0436.1000121 (2014).

3 - Warner DR, Mukhopadhyay P, Brock G, Webb C, Pisano MM, Greene RM. MicroRNA expression profiling of the developing murine upper lip. Development, Growth Differentiation  56:434-447 (2014). PMCID: PMC4379120

4 - Jin J-Z, Warner DR, Lu Q, Pisano MM, Greene RM Ding J. Deciphering TGF-β3 function in medial edge epithelium specification and fusion during mouse secondary palate development.  Develop Dynamics 243:1536-1543, (2014).  PMID: 25104574

5 - Seelan RS, Brock G, Appana SN, Mukhopadhyay P, Warner DR, Pisano MM & Greene RM.

Methylated microRNA genes of the developing murine palate. miRNA 3: 160-173 (2014). PMID: 25642850

6 - Greene RM and Kirschner RE. Molecular Strategies in the Study and Repair of Palatal Defects. In: Stem Cell Biology and Tissue Engineering in Dental Sciences, (editors: A. Vishwakarma, P. Sharpe, S. Shi, X Wang, M Ramalingam), Elsevier Press, Chapter 38; pp 485-498 (2015).

 7 - Warner DR, Ding J, Mukhopadhyay P, Brock G, Smolenkova, Seelan RS, Webb CL, Wittliff JL, Greene RM, and Pisano MM. Temporal expression of miRNAs in laser capture microdissected palate medial edge epithelium from TGFb3-null mouse fetuses.  miRNA 4:64-71 (2015). PMID: 26159804

 8 - Mukhopadhyay P, Greene RM, Pisano MM. Cigarette smoke induces proteasomal-mediated degradation of DNA methyltranferases and methyl CpG-/CpG domain-binding proteins in first branchial arch cells.  Reprod Toxicology 58:140-148 (2015). PMCID: PMC4690750

 9 - Greene RM, Pisano MP, Warner D. Genetic and Epigenetic Perspectives of Orofacial Clefting. In: Comprehensive Cleft Care, 2nd edition. (editors: Losee JE, Kirschner RE), CRC Press, Chapter 10, pp 185-205 (2016).

10 - Warner D, Smith S, Smolenkova I, Pisano MM, and Greene RM. Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression. Exp Cell Res 342:32-8 (2016). PMCID: PMC4818121

11 - Neal RE, Jagadapillai R, Chen J, Webb C, Stocke K, Greene RM, Pisano MM.  Developmental cigarette smoke exposure II:  Hippocampus proteome and metabolome profiles in adult offspring. Reprod Toxicology ( 65:436-447 (2016). PubMed PMID: 27208486.

12 - Neal RE, Jagadapillai R, Chen J, Webb C, Stocke K, Stocke K, Gambrell C, Greene RM, Pisano MM.  Developmental cigarette smoke exposure II:  Kidney proteome profile alterations in 6 month old adult offspring. Reprod Toxicology  65:425-435 (2016). PMID: 27208485

13 - Neal RE, Chen J, Webb C, Stocke K, Gambrell C, Greene RM, Pisano MM.  Developmental cigarette smoke exposure II:  Hepatic proteome profiles in 6 month old adult offspring. Reprod Toxicology  65:414-424 (2016).PMID: 27319396

14 - Greene RM and Pisano MM. Serotonin signaling as a target for craniofacial embryotoxicityIn: Handbook of Developmental Neurotoxicology, 2nd edition, (editors: Paule M, Wang C and Slikker W), Elsevier Press (accepted and in press) (2017).

15 - Mukhopadhyay P,Seelan R, Rezzoug F, Warner D, Brock G, Smolenkova I, Pisano MM, Greene RM. Determinants of orofacial clefting I: Effects of 5-aza-2/-deoxycytidine on cellular processes and gene expression during development of the first branchial arch. Reprod Toxicology67: 85-99 (2017). PMID: 27915011

16 - Seelan R, Mukhopadhyay P, Warner D, Smolenkova I, Pisano MM, Greene RM. Determinants of orofacial clefting II: Effects of 5-Aza-2’-deoxycytidine on gene methylation in the first branchial arch. Reprod Toxicology67:100-110 (2017). PMID: 27923600 


Imaging of frontal (top panels) and lateral (bottom panels) views of gestational days 9.5 and 11.5 murine embryonic facial structures.   The first branchial arch consists of a smaller maxillary process (yellow) and a larger mandibular process (green). Medial nasal processes (red); Lateral nasal processes (blue).