Courtney Griffin, Ph.D.
Cardiovascular Biology Research Program
Adjunct Assistant Professor, Department of Cell Biology, University of Oklahoma Health Sciences Center
Lab website: http://griffinc.omrf.org/
In my lab, we are interested in the development of blood vessels. Certain diseases require blood vessel development for their progression; tumors, for example, thrive on blood flow. In those situations, we want to know how to stop vessel growth in order to stop disease progression. At other times, such as when wounds are healing, vessel growth is necessary and positive. In those cases we want to learn how to build new vessels.
Blood vessel development is similar in mice and humans, so we use mice to study and manipulate vessels. Much of our work is carried out in mouse embryos, since they undergo rapid and easily visible blood vessel development.
Because we want to understand what genes are required for blood vessel development, we study certain enzymes that help turn genes on and off. These enzymes are specifically involved in relaxing DNA that is normally tightly coiled up in our cells. When DNA is relaxed, genes can be regulated. We use genetically engineered mice to shut down these enzymes that relax DNA in order to determine the effect on blood vessel development. We ultimately hope to identify the particular genes that these enzymes regulate during vascular development, since those genes would be important therapeutic targets for controlling the process of vessel growth.
B.A., Harvard University, Cambridge, MA, 1995
Ph.D., University of California, San Francisco, CA, 2001
Honors and Awards
1995 Magna cum laude with highest honors in Biology, Harvard College
1998-2001 American Heart Association Predoctoral Fellowship
2002-2005 National Research Service Award Postdoctoral Fellowship
2005-2006 American Heart Association Postdoctoral Fellowship
2006-2011 NIH Pathway to Independence Award
2011 TEDxOU: Epigenetics and the Influence of Our Genes
2013 J. Donald and Patricia Capra Award for Scientific Achievement
North American Vascular Biology Organization
Joined OMRF Scientific Staff in 2008
My lab is fundamentally interested in how blood vessels are made. In the adult, new vessel formation can be beneficial (e.g., during wound healing or ischemia) or detrimental (e.g., during tumor growth and diabetic retinopathy). Our goal, therefore, is to define genetic and molecular pathways that can lead to novel therapies promoting insufficient vascular growth or disabling pathogenic vascular growth.
Because many of the processes that occur during vascular development in the embryo are recapitulated when new blood vessels are formed in the adult, we use both embryonic and adult mouse models to study vascular development. We are currently utilizing mice with mutations in chromatin-remodeling enzymes to approach the field of vascular development from a unique perspective. Chromatin-remodeling enzymes are the catalytic subunits of multi-protein complexes that physically interact with regulatory elements of certain target genes throughout the genome. These complexes mediate transcriptional activation or repression of their target genes by manipulating the local chromatin structure so that large transcriptional machinery can gain access to the target gene promoter. We have demonstrated that at least one chromatin-remodeling enzyme plays an important role in embryonic vascular development, and we are systematically depleting the other major enzymes to determine their participation in vascular development. We are also interested in the function of these enzymes and complexes in the adult vasculature and will assess their role during both normal and pathological vascular growth. Finally, we are exploiting the physical interaction between chromatin remodeling complexes and their target genes to identify genes specifically involved in embryonic and adult vascular development. We anticipate that these complexes will elucidate the epigenetic control of genes already known to play important roles in vascular development and will reveal novel genes not previously recognized as mediators of vascular development.
* Liu X, Pasula S, Song H, Tessneer KL, Dong Y, Hahn S, Yago T, Brophy ML, Chang B, Cai X, Wu H, McManus J, Ichise H, Georgescu C, Wren JD, Griffin C, Xia L, Srinivasan RS, Chen H. Temporal and spatial regulation of epsin abundance and VEGFR3 signaling are required for lymphatic valve formation and function. Sci Signal 7:ra97, 2014. [Abstract]
Chen H, Griffin C, Xia L, Sathish SR. Molecular and cellular mechanisms of lymphatic vascular maturation. Microvasc Res 96C:16-22, 2014. [Abstract]
McBride J, Jenkins A, Liu X, Zhang B, Lee K, Berry WL, Janknecht R, Griffin C, Aston CE, Lyons T, Tomasek JJ, Ma JX. Elevated circulation levels of an anti-angiogenic SERPIN in patients with diabetic microvascular complications impairs wound healing through suppression of Wnt signaling. J Invest Dermatol 134:1725-1734, 2014. [Abstract]
Ingram KG, Curtis CD, Silasi-Mansat R, Lupu F, Griffin CT. The NuRD Chromatin-Remodeling Enzyme CHD4 Promotes Embryonic Vascular Integrity by Transcriptionally Regulating Extracellular Matrix Proteolysis. PLoS Genet 9:e1004031, 2013. [Abstract]
Davis RB, Curtis CD, Griffin CT. BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development. Development 140:1272-1281, 2013. [Abstract]
Curtis CD, Davis RB, Ingram KG, Griffin CT. Chromatin-remodeling complex specificity and embryonic vascular development. Cell Mol Life Sci 69:3921-3931,2012. [Abstract]
Curtis CD, Griffin CT. The chromatin-remodeling enzymes BRG1 and CHD4 antagonistically regulate vascular Wnt signaling. Mol Cell Biol 32:1312-1320, 2012. [Abstract]
Griffin CT, Curtis CD, Davis RB, Muthukumar V, Magnuson T. The chromatin-remodeling enzyme BRG1 modulates vascular Wnt signaling at two levels. Proc Natl Acad Sci U S A 108:2282-2287, 2011. [Abstract]
Griffin CT, Brennan J, Magnuson T. The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development. Development 135:493-500, 2008. [Abstract]
Cardiovascular Biology Research Program, MS 45
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7073
Fax: (405) 271-7417