Zoology and Physiology

College of Agriculture, Life Sciences, and Natural Resources

Brian Cherrington

Associate Professor

Office: BS 415
Lab: BS 429
(307) 314-9139
bcherrin@uwyo.edu

https://bdcherringtonlab.org

Education:

• 1996, B.A. Washington University, St. Louis, MO
• 2001, M.S. Colorado State University, Fort Collins, CO
• 2005, Ph.D.  Colorado State University, Fort Collins, CO

Research Interests:

My research focuses on determining the role of peptidylarginine deiminase (PAD) enzymes in female reproduction and associated diseases.  The PAD enzymes post-translationally convert positively charged arginine in target proteins to the neutral citrulline residue.  This reaction termed citrullination or deimination significantly alters target protein structure and function.  PAD expression in tissues such as the anterior pituitary gland, mammary gland, and uterus changes over the course of the female reproductive cycle.  The best-characterized targets for PADs are arginine residues in histone tails, which, when citrullinated, alter chromatin structure and gene expression.  Methodological advances have allowed for the identification of tissue-specific citrullinomes, which reveal that PADs citrullinate a wide range of enzymes and structural proteins to alter cell function.  In contrast to their important physiological roles, PADs and citrullinated proteins are also involved in several female specific diseases including autoimmune disorders and reproductive cancers.

We currently have three main projects in the lab:

1. Determine the role of PADs, citrullinated proteins, and anti-citrullinated protein antibodies (ACPA) in the cervicovaginal mucosa during the female reproductive lifecycle and investigate if they are involved in the etiology of rheumatoid arthritis.
2. Define how PAD and citrullinated proteins contribute to the female gonadotrope cell luteinizing hormone (LH) surge that is obligatory for ovulation.
3. Investigate whether PADs epigenetically regulate miRNA programs to stimulate expansion of the lactotrope cell population during pregnancy, which is ultimately required for initiation of lactation.

Teaching

Human Systems Physiology (ZOO 3115),

Mammalian Genomics (ZOO 4735/5735),

The Art and History of Medicine (HP 4152, J-Term study abroad).

Publications:

Christensen AO, Li G, Young CH, Snow B, Khan SA, DeVore SB, Edwards S, Bouma GJ, Navratil AM, Cherrington BD *, Rothfuss HM. Peptidylarginine deiminase (PAD) enzymes and Citrullinated proteins in female reproductive physiology and associated diseases. Biol Reprod. 2022 Sep 10:ioac173. doi: 10.1093/biolre/ioac173. Epub ahead of print. PMID: 36087287. * Corresponding author.

Okamoto Y, Devoe S, Seto N, Minarchick V, Wilson T, Rothfuss HM, Mohning MP, Arbet J, Kroehl M, Visser A, August J, Thomas SM, Charry LL, Fleischer C, Feser ML, Frazer-Abel AA, Norris JM, Cherrington BD, Janssen WJ, Kaplan MJ, Deane KD, Holers VM, Demoruelle MK. Association of Sputum Neutrophil Extracellular Trap Subsets With IgA Anti-Citrullinated Protein Antibodies in Subjects at Risk for Rheumatoid Arthritis. Arthritis Rheumatol. 2022 Jan;74(1):38-48. doi: 10.1002/art.41948. Epub 2021 Nov 25. PMID: 34369110; PMCID: PMC8712364.

Young CH, Snow B, DeVore SB, Mohandass A, Nemmara VV, Thompson PR, Thyagarajan B, Navratil AM, Cherrington BD. Progesterone stimulates histone citrullination to increase IGFBP1 expression in uterine cells. Reproduction. 2021 Jul 8;162(2):117-127. doi: 10.1530/REP-21-0132. PMID: 34034233; PMCID: PMC8284904.

Clay CM, Cherrington BD, Navratil AM. Plasticity of Anterior Pituitary Gonadotrope Cells Facilitates the Pre-Ovulatory LH Surge. Front Endocrinol (Lausanne). 2021 Feb 4;11:616053. doi: 10.3389/fendo.2020.616053. PMID: 33613451; PMCID: PMC7890248.

Li G, Young CH, Snow B, Christensen AO, Demoruelle MK, Nemmara VV, Thompson PR, Rothfuss HM, Cherrington BD. Identification and Characterization of the Lactating Mouse Mammary Gland Citrullinome. Int J Mol Sci. 2020 Apr 10;21(7):2634. doi: 10.3390/ijms21072634. PMID: 32290104; PMCID: PMC7177251.

Zhang X, Xiao H, Zhang X, E Q, Gong X, Li T, Han Y, Ying X, Cherrington BD, Xu B, Liu X, Zhang X. Decreased microRNA-125b-5p disrupts follicle steroidogenesis through targeting PAK3/ERK1/2 signalling in mouse preantral follicles. Metabolism. 2020 Jun;107:154241. doi: 10.1016/j.metabol.2020.154241. Epub 2020 Apr 15. PMID: 32304754.

Devore SB, Young CH, Li G, Sundararajan A, Ramaraj T, Mudge J, Schilkey F, Muth A, Thompson PR, Cherrington BD.  Histone citrullination represses miRNA expression resulting in increased oncogene mRNAs in somatolactotrope cells. Mol Cell Biol. 2018. Jul 9. pii: MCB.00084-18. doi: 10.1128/MCB.00084-18. PMID: 29987187. Selected as a Spotlight Article of significant interest in the September 2018 issue of MCB.

Acevedo-Rodriguez A, Kauffman AS, Cherrington BD, Laconi M, Borges CS, Roepke TA, Laconi M. Emerging insights into Hypothalamic-pituitary-gonadal (HPG) axis regulation and interaction with stress signaling. J Neuroendocrinol. 2018 Oct;30(10):e12590. doi: 10.1111/jne.12590.  PMID: 29524268.

Visit the lab website.