Joan Heller Brown, Ph.D.
Distinguished Professor and Past Chair
Program Director, NIH T32 in Pharmacological Sciences
My laboratory is interested in elucidating mechanisms underlying the regulation of cell growth, survival and inflammation by G-protein coupled receptors (GPCRs). We examine the signal transduction pathways by which specific GPCRs (for thrombin, LPA, S1P) that couple to activation of RhoA effect chronic changes in cellular responses that contribute to disease progression. Biochemical, cell and molecular techniques are used to identify signaling pathways and generate transgenic or knockout mice to assess their physiological role in heart disease and cancer. Molecular players of current interest are the small G-protein RhoA, the calcium regulated CaM kinase, and the transcriptional co-factors MRTFA and YAP, with focus on their roles in cardiac inflammation and glioblastoma stem cell and tumor growth.
Yu O.M., Benitez J.A., Plouffe S. W., Ryback D., Klein A., Smith J., Greenbaum J., Delatte B., Rao A., Guan K.L., Furnari F.B., Chaim O.M., Miyamoto S., Brown, J.H. YAP and MRTF-A, transcriptional co-activators of RhoA-mediated gene expression, are critical for glioblastoma tumorigenicity. Oncogene. Jun 11. doi: 10.1038/s41388-018-0301-5. (selected by Faculty of 1000). 2018.
Willeford A., Suetomi T., Nickle A., Hoffman HM, Miyamoto S., Brown J. H. CaMKIIδ-mediated inflammatory gene expression and inflammasome activation in cardiomyocytes initiate inflammation and induce fibrosis. JCI Insight, Volume 3, Issue 12:e97054, 2018.
Brand C. S., Tan V. P., Brown J. H., Miyamoto S. RhoA regulates Drp1 mediated mitochondrial fission through ROCK to protect cardiomyocytes. Cell Signal. Jun 25; 50: 48-57, 2018.
Suetomi, T., Willeford A.W., Brand C. S., Cho Y., Ross R. S., Miyamoto S., Brown J. H. Inflammation and NLRP3 inflammasome activation initiated in response to pressure overload by CaMKIIδ signaling in cardiomyocytes are essential for adverse cardiac remodeling. Circulation. 138: 2530-2544, 2018.
Suetomi T, Miyamoto S, Brown J.H., Inflammation in non-ischemic heart disease: initiation by cardiomyocyte CaMKII and NLRP3 inflammasome signaling, Am JPhysiol Heart Circ Physiol. Nov 1;317(5):H877-H890 2019.
Dalal, P.J., Sullivan, D.P., Weber, E.W., Sacks, D.B., Gunzer, M., Grumbach, I.M., Brown, J.H., Muller, W.A. Spatiotemporal restriction of endothelial cell calcium signaling is required during leukocyte transmigration. J Exp Med. Jan 4;218(1):e20192378, 2021.
Calcagno, D.M, Zhang, C., Toomu, A., Huang, K., Ninh, V.K., Miyamoto, S., Aguirre, A.D., Fu, Z., Brown, J.H., King, K.R. SiglecF(HI) Marks Late-Stage Neutrophils of the Infarcted Heart: A Single-Cell Transcriptomic Analysis of Neutrophil Diversification. J Am Heart Assoc. Feb 16;10(4):e019019, 2021.
Ninh, V.K., Brown, J.H. The contribution of the cardiomyocyte to tissue inflammation in cardiomyopathies. Curr Opin Physiol. Feb;19:129-134, 2021.
Brown, J.H., Miyamoto, S. Splicing and Dicing: A Deeper Dive Into CaMKIIδ and Cardiac Inflammation. Circ Res. Mar 18;130(6):904-906. doi: 10.1161/CIRCRESAHA.122.320881, 2022.
Moshensky, A., Brand, C.S., Alhaddad, H., Shin, J., Masso-Silva, J.A., Advani, I., Gunge, D., Sharma, A., Mehta, S., Jahan, A., Nilaad, S., Olay, J., Gu, W., Simonson, T., Almarghalani, D., Pham, J., Perera, S., Park, K., Al-Kolla, R., Moon, H., Das, S., Byun, M., Shah, Z., Sari, Y., Brown, J.H., Crotty, Alexander L.E. Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice. Elife. Apr 12;11:e67621. doi: 10.7554/eLife.67621, 2022.