Alan Hall (molecular biologist)
Alan K Hall (Born on April 11, 1953) attended Saint Peter’s School in Huntingdon, Cambridgeshire, England. He went on to study Biological Sciences at Aston University in Birmingham, where his collaborative research studies showed that steroids and ions can affect cell division (1).
After gaining an honors degree he studied for his Ph.D. at Hull University in the Department of Zoology. It is here that he discovered the rapid effects of prostaglandin F upon the ovarian production of progesterone in vitro and in vivo (2,3). In 1978 ge took up post-doctoral studies at Yale University as a Ford Foundation Fellow. He studied under the directorship of the late Harold Behrman (died 2008).
Career[edit]
Whilst at Yale (Department of Obstetrics Gynecology and Pharmacology) Hall discovered the direct trophic actions of adenosine on ovarian steroidogenesis (4) and the phenomenon called culture-induced senstization (5). He l spent some time as a Wellcome Trust Research Fellow at The Strangeways Research Laboratory at Cambridge University. It is here that he discovered that the vitamin D3 metabolite, 24, 25-dihhydroxyvitamin D3 can exert stimulatory actions upon bone formation (6).
In 1984, as a Fulbright Fellow, Hall worked in Professor Anthony W Norman’s laboratory at the University of California, Riverside. It was here that he helped clone the gene encoding calcium binding protein7 and studied the molecular actions of vitamin D metabolites.
Hall then joined the research staff at the Roche Institute of Molecular Biology (RIMB) in Nutley, New Jersey. It is here that he discovered that the vitamin A metabolite, retinoic acid could modulate a protein called thymosin beta-10 in brain cancer cells. He found that retinoic acid halted the growth of human and rat brain cancer cells (8,9) and that the gene was developmentally modulated in the brain (10).
Hall continued his research at the University of Medicine and Dentistry of New Jersey ) in Newark under the direction of the late Joseph J Seebode Funded by the National Institutes of Health and the C R Bard Company and as Director of the Urology Research Laboratory, Hall went on to discover that thymosin beta-10/4 gene expression is linked to the spread of cancer cells throughout the body (metastasis) (11). In collaboration with Sylvia Christakos, Hall also found that retinoid receptors are involved in the modulation of the calbindin gene by vitamin D3 (12) and is modulated by gonadotropic hormones in the ovary (13).
Hall transferred his laboratory operations to the University of Cambridge (Pharmacology Department) in England. Here he discovered that cancer cells could be coaxed into dying when the thymosin beta-10 gene was overexpressed by using SV40-driven expression vectors (14). He demonstrated that thymosin-beta-10 induced the collapse of the cell actin cytoskeleton and this in turn boosted the death (apoptosis) of cancer cells in response to chemotherapeutic drugs (15,16).
He and his coworkers also cloned and sequenced the human thymosin beta-10 gene and showed that it contained DNA response elements sensitive to the occupied retinoic acid receptor (17). Subsequent to this pioneering work, other studies have shown that thymosin beta-10 is a marker for breast cancer and a progression marker for cutaneous melanoma18 and is implicated in the metastatic spread of non-small cell lung cancer19. Other research shows that thymosin beta-10 inhibits angiogenesis and tumor growth (20) and these actions derive from specific apoptotic-amino acid residues present in the thymosin protein molecule (21). More recent research has demonstrated that suppression of thymosin beta-10 protein levels increases the metastatic spread of cancer cells (22).
Hall’s original research into the relationship between these tumor-specific proteins have thus been instrumental in illuminating at least one pathway by which cancer cells spread around the body.
References[edit]
Sources[edit]
1. Morgan J I, Hall, A K & Perris, A D (1977). The ionic dependence and steroid blockade of cyclic nucleotide-induced mitogenesis in isolated rat thymic lymphocytes. Journal of Cyclic Nucleotide Research, 3: 303-314.
2. Hall, A K & Robinson J (1979). Functional autolysis in the pseudo pregnant rat: effects of prostaglandin F and 16-aryloxyprostaglandin F in vitro. Journal of Endocrinology 90: 359-366.
3. Robinson J, Hall A K, Merry B J & Lightfoot M E (1981), The dynamics of progesterone metabolism in the pseudo pregnant rat. Journal of Endocrinology 81: 157-165.
4. Hall, A K & Behrman H R (1981), Purine amplification of LH action in ovarian luteal cells. Journal of Biological Chemistry 256: 10390-10398.
5. Hall, A K & Behrman H R (1981), Culture sensitization and inhibition of luteinizing hormone responsive production of cyclic AMP in luteal cells by luteinizing hormone, prostaglandin F and synthetic LHRH.Journal of Endocrinology 88: 27-38.
6. Dickson I R, Hall, A K & Jande, S (1982). Influence of Dihydroxylated vitamin D metabolites on bone formation. Calcified Tissue International 36: 114-122.
7. Theofan, G., Hall A K, King M W & Norman A W (1985), Cloning of cDNAs to the chick intestinal 28K vitamin D3- induced calcium binding protein (CaBP) mRNA and their use to study the regulation of the CaBP message, In: Vitamin D: Biochemical, Chemical, Clinical Update, Walter de Gruyter Press, Inc., Berlin, pp 333–342.
8. Hall A K, Chen, S-C, Hempstead, J & Morgan (1991), Retinoic Acid Regulates Thymosin Beta-10 Levels in Rat Neuroblastoma Cells, Journal of Neurochemistry 56: 462-468.
9. Hall A K, Hempstead, J & Morgan J I (1990). Thymosin beta-10 levels in developing human brain and its regulation by retinoic acid in the HTB-10 neuroblastoma, Molecular Brain Research 8: 129-135.
10. Hall, A K (1991). Developmental regulation of thymosin beta-10 in the human brain, Molecular Brain Research 9: 175-177.
11. Hall, A K (1991). Differential Expression of Thymosin Genes in Human Tumors and in the Developing Human Brain, International Journal of Cancer 48: 672-677.
12. Hall A K, Wang, Y-Z, Gill, R K & Christakos S (1991). Modulation of Calbindin-like Expression by Retinoic Acid in Neuronal Cells Over-Expressing A Retinoid Acid Receptor, Neuroscience Soc Meeting, San Diego, 17 (2), p1502.
13. Hall A K, Aten R & Behrman H R (1991), Differential Modulation of Thymosin Genes in the Immature Rat Ovary by Gonadotropins, Molecular Cellular Endocrinology 79: 37- 43.
14. Hall A K(1995). Thymosin Beta-10 Accelerates Apoptosis, Cellular Molecular Biology Research 41 (3): 167-180.
15. Hall A K(1996). Liarozole Amplifies Retinoic Acid Induced Apoptosis in Human Prostate Cancer Cells, AntiCancer Drugs 7: 312-320.
16. Hall A K(1994). Molecular Interactions between G-Actin, DNase 1 and Thymosins in Apoptosis. Medical Hypotheses 43: 125-131.
17. Condon M R, Lysz T W & Hall A K (1991). Cloning of the Thymosin Beta-10 Gene: Characterization of its Structure and Nucleotide Sequence, Soc Neurosci 17 (2): 457.16; page 1152.
18. Weterman, M A J et al. (1993). Thymosin beta-10 Expression in Melanoma Cell Lines and Melanocytic Lesions: A New Progression Marker for Human Cutaneous Melanoma, Int J Cancer 53: 278-284.
19. Ji P et al. (2002). Malat-1 a novel noncoding RNA and Thymosin beta-4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22: 8031-8041.
20. Lee, S H et al. (2005). Thymosin beta-10 inhibits angiogenesis and tumor growth by interfering with Ras function. Cancer Research 65 (1): 137-148.
21. Rho, S B et al. (2005). The investigation of apoptosis-related residues in human thymosin beta-10 by mutational analysis and computer modeling. Journal Biological Chemistry 280: 34003-34007.
22. Sribenja S et al. (2013). Suppression of thymosin beta-10 increases cell migration and metastasis of cholangiocarcinoma. British Medical Council (BMC) Cancer 13: 430.
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