Department: Pharmacology, Physiology and Toxicology
Research Clusters: Cardiovascular Disease, Obesity, and Diabetes; Neuroscience and Developmental Biology (Cluster Coordinator)
Office: BBSC 435H | Laboratory: BBSC 411
Phone: (304) 696-3523 | Fax: (304) 696-7391
Personal website: http://regleton.googlepages.com/
My studies over the last decade have focused on the barrier systems of the brain. In particular I am intersted in two key research areas of the blood brain barrier (BBB), drug delivery and role of the BBB in disease. Like everyone else I first heard about the BBB as an undergraduate student. The belief then (at least at the teaching level) was that the BBB was a static barrier, only really of importance for drug delivery, and maintaining “immune privilege” of the brain. Over the last 20 years there has been a huge growth in defining what the barriers are and how they function. The concept of the BBB is constantly evolving. Hopefully this site will be able to evolve in concert with BBB research and supply a resource for people who would like to keep abreast of current concepts.
Major areas of BBB research that really interest me at the moment are:
- The concept of the neurovascular unit (NVU) is of major interest to me. The role of other cells (astrocytes, pericytes) in regulating barrier function has been understood for some time. Several recent studies have now shown that other brain cells (neurons, microglia, and various white blood cells) also play a major role in regulating the BBB. This has led to the understanding that the BBB is actually a complex, highly modulated barrier system that is dependent on interaction with its cellular neighbors to maintain its phenotype, hence the concept of the NVU was born. Of interest to me is understanding what the interactions and signaling pathways are that regulate all of this.
- What is the role of the BBB /NVU in disease progression? A number of papers have now been published showing changes in BBB structure and function during animal models of disease, or in some cases, clinically. What really hasn’t been addressed in many cases is if the BBB changes play an essential role in disease progression, or are a by product of disease progression.
MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway. Brown KC, Lau JK, Dom AM, Witte TR, Luo H, Crabtree CM, Shah YH, Shiflett BS, Marcelo AJ, Proper NA, Hardman WE, Egleton RD, Chen YC, Mangiarua EI, Dasgupta P.
The α7-nicotinic acetylcholine receptor and MMP-2/-9 pathway mediate the proangiogenic effect of nicotine in human retinal endothelial cells. Dom AM, Buckley AW, Brown KC, Egleton RD, Marcelo AJ, Proper NA, Weller DE, Shah YH, Lau JK, Dasgupta P. Invest Ophthalmol Vis Sci. 2011 Jun 22;52(7):4428-38. Print 2011 Jun.
Angiogenic activity of nicotinic acetylcholine receptors: implications in tobacco-related vascular diseases. Egleton RD, Brown KC, Dasgupta P. Pharmacol Ther. 2009 Feb;121(2):205-23. Epub 2008 Nov 14. Review.
Nociceptive inhibition prevents inflammatory pain induced changes in the blood-brain barrier. Campos CR, Ocheltree SM, Hom S, Egleton RD, Davis TP. Brain Res. 2008 Jul 24;1221:6-13. Epub 2008 May 17.
Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis. Egleton RD, Brown KC, Dasgupta P. Trends Pharmacol Sci. 2008 Mar;29(3):151-8. Epub 2008 Feb 11. Review.
Pathophysiology of the blood-brain barrier: animal models and methods. Hawkins BT, Egleton RD. Curr Top Dev Biol. 2008;80:277-309. Review.
Tight junctions contain oligomeric protein assembly critical for maintaining blood-brain barrier integrity in vivo. McCaffrey G, Staatz WD, Quigley CA, Nametz N, Seelbach MJ, Campos CR, Brooks TA, Egleton RD, Davis TP. J Neurochem. 2007 Dec;103(6):2540-55. doi: 10.1111/j.1471-4159.2007.04943.x.
Peripheral inflammatory hyperalgesia modulates morphine delivery to the brain: a role for P-glycoprotein. Seelbach MJ, Brooks TA, Egleton RD, Davis TP. J Neurochem. 2007 Sep;102(5):1677-90.
Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats. Hom S, Fleegal MA, Egleton RD, Campos CR, Hawkins BT, Davis TP. Am J Physiol Regul Integr Comp Physiol. 2007 May;292(5):R1881-92. Epub 2007 Jan 18.
Increased blood-brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases. Hawkins BT, Lundeen TF, Norwood KM, Brooks HL, Egleton RD. Diabetologia. 2007 Jan;50(1):202-11. Epub 2006 Dec 2.
Nancy Proper – Research Technician
Aileen Marcelo – Ph.D. candidate