Keith Solomon's research is focused on the molecular mechanisms underlying cholesterol’s role in geriatric diseases including prostate cancer (PCa), osteoporosis, vascular calcification and BPH. We hypothesize that there are three principal ways that cholesterol affects normal & pathological cellular activities: 1) as a structural element in membrane domains called lipid rafts. The structure of cholesterol allows for the close packing of fatty acids, which in turn form ordered membrane domains that are neither liquid-crystalline nor gel state, but instead are in a liquid-ordered state. By causing transition to this state cholesterol enables the formation of membrane substructures with unique properties; 2) as the molecular precursor of steroid hormones. We hypothesize that de novo cholesterol synthesis is occurring at lesion sites, especially in prostatic tumors. All the enzymes required for androgen synthesis are expressed in castration-resistant PCa and we hypothesize that cholesterol is fueling androgen synthesis by providing a required and rate limiting component; 3) as a promoter of angiogenesis. Based on our own work we hypothesize that hypercholesterolemia leads to pathological angiogenesis.
About Keith Solomon
Keith R. Solomon received a PhD in immunology from Harvard University.
- Pelton, K., Di Vizio, D., Insabato, L., Schaffner, C.P., Freeman, M.R. and Solomon, K.R. Ezetimibe reduces enlarged prostate size in an animal model of benign prostatic hyperplasia. 2010 (published online 8/10 J. Urology).
- Solomon, K.R., Pelton, K., Boucher, K., Joo, J., Tully, C., Zurkowski, D., Schaffner, C.P., Kim, J., and Freeman, M.R. Ezetimibe Is An Inhibitor of Tumor Angiogenesis. Amer. J. Path. 2009, 174:1017-1026.
- McLellan , D. L., Adam, R. M., Steen H., Gygi, S. P., Garlick M. Freeman, M. R. and Solomon, K. R. A Quantitative Proteomic Analysis of Growth Factor-Induced Compositional Changes in Lipid Rafts of Human Smooth Muscle Cells. Proteomics. 2005, 5:4733-4742.
- Freeman MR, Solomon KR. Cholesterol and prostate cancer. Journal of Cell Biochemistry 2004; 91: 54-69.
- Zhuang L, Lin J, Lu ML, Solomon KR, and Freeman MR. Cholesterol-rich lipid rafts regulate growth factor-activated Akt signaling and cell survival in human prostate cancer cells. Cancer Research 2002; 62: 2227-2231.
- Solomon KR, Danciu TE, Adolphson LD, Hecht LE, Hauschka PV. Caveolin-enriched membrane signaling complexes in human and murine osteoblasts. Journal of Bone Mineral Research 2000; 15: 2380-2390.