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Professor Emeritus of Pharmacology and Cancer Biology
Associate Director for Basic Research Emeritus, Duke Cancer Institute
Duke University School of Medicine
Durham, NC 27710
The Means laboratory is interested in the study of cell signaling cascades that regulate cell proliferation, differentiation or function and how alterations in these pathways contribute to development of cancer and other diseases such as obesity. It is hoped that an understanding of these pathways may provide clues to novel targets that may be amenable to drug discovery.
The current primary focus of the research effort is to investigate the cellular and genetic mechanisms that govern regulation of the CaM kinase cascade. We explore cell surface receptor-mediated systems that elevate intracellular calcium, activate CaM and initiate pathways involving members of the CaM kinase cascade leading to events that alter cell fate and/or function. The proteins involved in these cascades are the upstream kinases CaMKK1 and CaMKK2 and the downstream kinases CaMKI, CaMKIV and AMPK. Examples of such projects now under study are how CaMKK2 and its downstream kinase targets regulate stem cells, energy expenditure, metabolism and inflammation.
Kokobu, M., Nishio, M., Ribar, T.J., Anderson, K.A., West, A.E. and Means. A.R. (2009) BDNF Mediated Cerebellar Granule Cell Development is Impaired in Mice Null for CaMKK2 or CaMKIV. J Neurosci 29:8901-8913.
Colomer J, Schmitt AA, Toone EJ, Means AR. (2010) Identification and inhibitory properties of a novel Ca(2+)/calmodulin antagonist. Biochemistry 49(19):4244-54.
Frigo D, Howe M, Brunner A, Chushman I, Wittmann B, Wang Q, Brown M, Means AR and McDonnell DM (2010) Ca2+/Calmodulin-Dependent Protein Kinase Kinaseβ Mediated Activation of AMP-Activated Kinase is Required for Androgen-Dependent Migration of Prostate Cancer Cells. Cancer Research 71:528-537.
Oury F, Yadav VK, Zhou B, Liu XS, Guo XE, Wang Y, Tecott LH, Schutz G, Means AR, Karsenty G (2010) CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons. Genes and Development 24:2330-2342.
Todd LR, Damin MN, Gomathinayagam R, Horn SR, Means AR, Sankar U. (2010) Growth factor erv1-like modulates Drp1 to preserve mitochondrial dynamics and function in mouse embryonic stem cells. Mol Biol Cell. 2010 Apr;21(7):1225-36.
Teng EC, Todd LR, Ribar TJ, Lento W, Dimascio L, Means AR, Sankar U. (2011) Gfer Inhibits Jab1-Mediated Degradation of p27kip1 to Restrict Proliferation of Hematopoietic Stem Cells. Mol Biol Cell 22:1310-1320.
Sankar U and Means AR (2011) Gfer is a critical regulator of HSC proliferation. Cell Cycle 15:10(14):2263-2268.
Green MF, Scott JW, Steel R, Oakhill J, Kemp BE and Means AR (2011) Ca2+/calmodulin-dependent protein kinase kinase beta is regulated by multi-site phosphorylation. J Biol Chem 286(32):28066-28079.
Girardini JE, Napoli M, Piazza S, Rustighi A, Marotta C, Radaelli E, Capaci V, Jordan L, Quinlan P, Thompson A, Mano M, Rosato A, Crook T, Scanziani E, Means AR, Lozano G, Schneider C, Del Sal G (2011) A Pin1/Mutant p53 axis promotes aggressiveness in breast cancer. Cancer Cell 20:79-91.
Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi S, Khan N, Li G-M, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R and Pulendra B (2011) Systems biology of vaccination for seasonal influenza in humans. Nature Immunol 12(8):786-795.
Teng BL, Hacker KE, Chen S, Means AR and Rathmell WK (2011) Tumor suppressive activity of prolyl isomerase Pin1 in renal cell carcinoma. Mol Oncol. In Press.
Green MF, Anderson KA and Means AR (2011) Characterization of the CaMKKbeta-AMPK signaling complex. Cell Signal. In Press.
Teng EC, Racioppi L and Means AR (2011) A cell-intrinsic role for CaMKK2 in granulocyte lineage commitment and differentiation. J Leukoc Biol. In Press.
Lin F, Ribar TJ and Means AR (2011) The Ca2+/calmodulin-dependent protein kinase kinase, CaMKK2, inhibits preadipocyte differentiation. Endocrinology. In Press.