Rosalyn M. Adam, Ph.D.
Collaborator
Associate Director, Urology Research
Children's Hospital Boston
Assistant Professor of Surgery
Harvard Medical School

John F. Enders Research Building, Rm 1077
300 Longwood Avenue
Boston, MA 02115
617-919-2019 (office)
617-730-0238 (fax)
rosalyn.adam@childrens.harvard.edu

Research in the Adam laboratory is focused on understanding mechanisms of diseases in the lower urinary tract. Our group is interested in the interface between kinase signaling and transcriptional regulation and how the resulting signaling networks are subverted in disease. My graduate training, conducted under the sponsorship of the Cancer Research Campaign at the University of Southampton in the UK, focused on mechanisms of tumor cell activation by the heparin-binding EGF-like growth factors, amphiregulin and heparin-binding EGF-like growth factor (HB-EGF). On joining Children’s Hospital Boston in 1996, I continued my studies of growth factor function within the context of urologic diseases such as prostate cancer, bladder cancer and bladder hypertrophy. These studies led to the identification of several novel functions for HB-EGF, including the demonstration that the growth factor could stimulate androgen-independent growth and neuroendocrine differentiation of prostate cancer cells in vitro and in vivo. These are both critical processes in prostate cancer progression and implicate HB-EGF in the transition to hormone-refractory disease. We also showed, in a separate study, that a nuclear form of HB-EGF is associated with aggressive bladder cancer. This was the first report in the literature describing nuclear localization of HB-EGF in any cell type or tissue and it strongly suggested a novel functional role for HB-EGF in the nucleus.A more recent study identified the adaptor protein Sh3gl2/endophilin A1 as a potential regulator of epidermal growth factor receptor (EGFR) signaling in bladder cancer. In addition to urologic oncology research, my group is also interested in understanding the regulation of gene expression in bladder smooth muscle exposed to so-called “hypertrophic” stimuli, such as mechanical stretch and growth factor stimulation. These studies relate to the mechanisms underlying pathologic remodeling of the bladder wall under conditions of urinary tract obstruction and their ultimate goal is to identify critical signaling nodes that could be targeted for therapeutic benefit.

Selected Publications

1) Adam, R. M., Borer, J. G., Williams, B. J., Eastham, J. A., Loughlin, K. R. and Freeman, M. R. (1999). Amphiregulin is coordinately expressed with heparin-binding EGF-like growth factor in the interstitial smooth muscle of the human prostate. Endocrinology 140: 5866-5875.

2) Park, J. M., Adam, R. M., Peters, C. A., Guthrie, P. D., Sun, Z., Klagsbrun, M. and Freeman, M.R. (1999) Activator Protein-1 mediates stretch-induced expression of heparin-binding EGF-like growth factor in bladder smooth muscle cells. American Journal of Physiology (Cell Physiology) 277: C294-C301.

3) Adam, R.M., Kim, J., Lin, J., Orsola, A., Rice, D.C. Zhuang, L. and Freeman, M.R. Heparin-binding EGF-like growth factor stimulates androgen-independent prostate tumor growth and antagonizes androgen receptor function. Endocrinology 143 (12): 4599-4608.

4) Adam, R.M., Danciu, T., McLellan, D.L., Borer, J.G., Lin, J., Zurakowski, D., Weinstein, M.H., Rajjayabun, P.H., Mellon, J.K. and Freeman, M.R. (2003). A nuclear form of the heparin-binding EGF-like growth factor precursor is a feature of aggressive transitional cell carcinoma. Cancer Research 63: 484-90.

5) Adam, R.M.,* Roth, J.A., Cheng, H-L., Rice, D.C., Khoury, J., Bauer, S.B., Peters, C.A. and Freeman, M.R. (2003) Signaling through PI3K-Akt mediates stretch- and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells. Journal of Urology 169, 2388-93. * Corresponding author.

6) Adam, R.M., Eaton, S.H., Estrada, C.R., Nimgaonkar, A., Shih, S-C., Smith, L.E.H., Kohane, I.S., Bagli, D. and Freeman, M.R. (2004) Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells. Physiological Genomics 20 (1), 36-44.

7) Estrada, C.R., Salanga, M., Bielenberg, D.R., Harrell, W.B., Zurakowski, D., Zhu, X., Palmer, M.R., Freeman, M.R. and Adam, R.M. (2006) Behavioral profiling of human transitional cell carcinoma ex vivo. Cancer Research 66, 3078-3086.

8) Adam, R.M., Mukhopadhyay, N.K., Kim, J., Di Vizio. D., Cinar, B., Boucher, K., Solomon, K.R. and Freeman, M.R. (2007) Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Research 67, 6238-6246.

9) Kanematsu, A., Ramachandran, A. and Adam, R.M. (2007) GATA-6 mediates human bladder smooth muscle differentiation: Involvement of a novel enhancer element in regulating alpha-smooth muscle actin gene expression. American Journal of Physiology Cell Physiology 293(3): C1093-C1102.

10) Ramachandran, A., Ranpura, S.A., Gong, E.M., Mulone, M.D., Cannon Jr, G.M. and Adam, R.M. An Akt- and Fra-1-dependent pathway mediates PDGF-induced expression of thrombomodulin, a novel regulator of smooth muscle cell migration. (Manuscript under review).

top