Rosalyn 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

After a false start in Dental School (!), I received my Bachelor’s degree in cell biology and biochemistry from the University of St. Andrews in Scotland. Having decided the academic life was for me, I ventured south to do my PhD at the University of Southampton in England under the supervision of Dr. Donna Davies, where my studies focused on mechanisms of tumor cell activation by the heparin-binding EGF-like growth factors. Since my arrival in Boston in 1996 or a postdoctoral fellowship in the Freeman lab, I have continued my studies of growth factor function within the context of urologic diseases such as prostate cancer, bladder cancer and bladder hypertrophy. Over the past 7 years, my colleagues and I have identified novel functions for the protein, heparin-binding EGF-like growth factor (HB-EGF) in two separate diseases of the genitourinary tract. Firstly, we showed that HB-EGF stimulates 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. Secondly, we recently reported that a nuclear form of HB-EGF is associated with aggressive bladder cancer. This study is the first report in the literature describing nuclear localization of HB-EGF in any cell type or tissue and it strongly suggests a novel functional role for HB-EGF in the nucleus. In addition to urologic oncology research, I am also interested in understanding the regulation of gene expression in bladder smooth muscle cells 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) AP-1 mediates stretch-induced expression of heparin-binding EGF-like growth factor in bladder smooth muscle cells. American Journal of Physiology 277 (Cell Physiol. ): C294-301.

3) Adam, R.M., Kim, J., Lin, J., Orsola, A., Rice, D.C., and Freeman, M.R. (2002) Heparin-binding EGF-like growth factor stimulates androgen-independent prostate tumor growth and antagonizes androgen receptor function. Endocrinology 143:4599-4608.

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 169:2388-2393. * 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.

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 (6): 3078-3086.

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 (13): 6238-6246.

Kanematsu, A., Ramachandran, A. and Adam, R.M. (2007) GATA-6 regulation of contractile protein expression in smooth muscle cells is modulated by cAMP. American Journal of Physiology Cell Physiology (in press).

top