Office: BS 416A
Lab: BS 429
B.A. Washington University in St. Louis
M.S. Colorado State University
Ph.D. Colorado State University
Postdoctoral University of California, San Diego and Cornell University
The research focus in my laboratory is to understand hormonal and epigenetic control of lactation. During lactation, mammary epithelial cells produce vast amounts of proteins and lipids which are critical for neonatal nutrition and survival. At parturition, the levels of the hormone prolactin increase in new mothers and induce the expression of milk proteins such as the caseins and whey acidic protein; yet many of the molecular mechanisms necessary for regulating the production and secretion of milk components is poorly understood.
My lab is particularly interested in the role of a family of enzymes called Peptidylarginine Deiminases (PADs) in lactation. The PAD enzymes post-translationally convert positively charged arginine and methyl-arginine amino acids to the neutral, non-standard residue citrulline. Further, past research has shown that expression levels of the PAD enzymes change over the course of the estrous cycle in multiple reproductive tissues such as the anterior pituitary gland, mammary gland, and uterus suggesting direct regulation of PAD expression by reproductive hormones. In terms of lactation, in the mouse mammary gland, PAD expression surges following birth and achieves over a 4-fold increase in expression by day 9 of lactation. During lactation, the PAD enzymes appear to influence critical molecular events not only in the mammary epithelial cell’s cytoplasm but also in the nucleus.
In the nucleus of human breast epithelial cells, PADs are known mediators of chromatin remodeling and play an important role in epigenetic gene expression. Thus, the lab is using genome wide approaches to identify target genes expressed only during lactation which are specifically regulated by PAD enzymes. Currently, we believe that following parturition the rise in maternal prolactin induces PAD expression which, in turn, functions as a co-regulator of genes involved in the production and secretion of milk components which are critical for neonatal survival across all mammalian species.
Another research focus of the lab is to understand the role that PAD enzymes play in the cytoplasm of secretory reproductive tissues such as lactotrophs in the anterior pituitary gland and mammary epithelial cells. Calcium is a critical molecular signal for secretion of prolactin from lactotrophs and milk from mammary epithelial cells. Interestingly, the PAD enzymes are highly dependent on Calcium for enzymatic activity. We are currently investigating if the cytoplasmic function of PAD enzymes is to post-translationally modify cytoskeletal architecture to induce vesicle secretion.
Human Systems Physiology (ZOO 3115) and Writing in Biological Sciences (ZOO 4100).
Zhang X, Gamble MJ, Stadler S, Cherrington BD, Causey CP, Thompson PR, Allis CD, Kraus WL, Coonrod SA. Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-fos expression in breast cancer cells. PLoS Genet. 2011 Jun;7(6):e1002112.
Cherrington BD, Morency E, Struble AM, Coonrod SA, Wakshlag JJ. Potential role for peptidylarginine deiminase 2 (PAD2) in citrullination of canine mammary epithelial cell histones. PLoS One. 2010 Jul 26;5(7):e11768.
Navratil AM, Song H, Hernandez JB, Cherrington BD, Santos SJ, Low JM, Do MH, Lawson MA. Insulin augments gonadotropin-releasing hormone induction of translation in Lbeta T2 cells. Mol Cell Endocrinol. 2009 Nov 13;311(1-2):47-54.
Lents CA, Farmerie TA, Cherrington BD, Clay CM. Transcriptional activity of the murine gonadotropin-releasing hormone receptor gene promoter is regulated by Oct-1 acting at core homeodomain DNA-binding sites at various locations. Endocrine. 2009 Jun;35(3):356-64.
Cherrington BD, Bailey JS, Diaz AL, Mellon PL. NeuroD1 and Mash1 temporally regulate GnRH receptor gene expression in immortalized mouse gonadotrope cells. Mol Cell Endocrinol. 2008 Nov 25;295(1-2):106-14.
Albertson AJ, Navratil A, Mignot M, Dufourny L, Cherrington B, Skinner DC. Immunoreactive GnRH type I receptors in the mouse and sheep brain. J Chem Neuroanat. 2008 Jul;35(4):326-33.
Cherrington BD, Farmerie TA, Clay CM. A specific helical orientation underlies the functional contribution of the activin responsive unit to transcriptional activity of the murine gonadotropin releasing hormone receptor gene promoter. Endocrine. 2006 Jun;29(3):425-33.
Cherrington BD, Farmerie TA, Lents CA, Cantlon JD, Roberson MS, Clay CM. Activin responsiveness of the murine gonadotropin-releasing hormone receptor gene is mediated by a composite enhancer containing spatially distinct regulatory elements. Mol Endocrinol. 2005 Apr;19(4):898-912.
Ellsworth BS, White BR, Burns AT, Cherrington BD, Otis AM, Clay CM. c-Jun N-terminal kinase activation of activator protein-1 underlies homologous regulation of the gonadotropin-releasing hormone receptor gene in alpha T3-1 cells. Endocrinology. 2003 Mar;144(3):839-49.