Robert Clarke (academic) explained

Robert Clarke
Nationality:Northern Irish
Occupation:Cancer researcher and academic administrator
Awards:Fellow, American Association for the Advancement of Science
Education:B.S., Biological Sciences
M.S., Biochemistry
Ph.D., Biochemistry
D.Sc., Biochemistry
Alma Mater:Ulster University
Queen's University Belfast
Workplaces:The Hormel Institute, University of Minnesota
Georgetown University

Robert Clarke is a Northern Irish cancer researcher and academic administrator. He is the executive director of The Hormel Institute, a professor of biochemistry, Molecular Biology and Biophysics at the University of Minnesota,[1] and an adjunct professor of oncology at Georgetown University.

With his work focused in breast cancer research, Clarke studies how hormones (endogenous and exogenous) and related factors affect breast cancer. He has authored over 340 publications,[2] and has 5 patents awarded. His research primarily focuses on determining an individual patient’s prognosis and the likelihood that they will respond to specific systemic therapies. His laboratory also studies drug resistance and the role of cell-cell communication in affecting dormancy and responsiveness to endocrine therapies breast cancers that express the estrogen receptor.[3]

Clarke is an elected Fellow of American Association for the Advancement of Science, the Royal Society of Chemistry, the Royal Society of Medicine, and the Royal Society of Biology. He is a Senior Editor for the journal Cancer Research.[4]

Education

Clarke studied at the University of Ulster, and received his bachelor's degree in biological sciences in 1980. He then enrolled at Queen’s University of Belfast, and earned a M.Sc. in 1982, a Ph.D. in 1986, and a D.Sc. in 1999 (each in biochemistry). He completed his postdoctoral training at the Medical Breast Section of the National Cancer Institute in 1988.[1]

Career

Following his postdoctoral training, Clarke joined Georgetown University School of Medicine as an assistant professor of physiology and biophysics, and was promoted to associate professor of oncology in 1995, and to professor in 1999. In 2020, he held an appointment at Georgetown University as an adjunct professor of oncology.[1]

Clarke also held several administrative appointments in his career. He served as secretary/treasurer of the Georgetown University Senate from 2004 till 2007, as associate vice president of GUMC and director of Biomedical Graduate Research Organization from 2007 till 2019, as co-leader of Breast Cancer Program 2006 till 2020, and as dean for research 2011 till 2019 at Georgetown University. Since 2020 he serves as executive director of The Hormel Institute, University of Minnesota.[1]

Research

Clarke's work is focused on how hormones (endogenous and exogenous) and related factors affect breast cancer. He initially focused on the interactions of hormones and anticancer drugs, and then expanded the work into studies of the underlying cellular and molecular mechanisms that explain how breast cancers become resistant to hormone and cytotoxic therapies. He and his colleagues have developed a series of hormone resistant breast cancer models that are now used in the field.[5] [6] [7]

Breast cancer

Clarke’s research team and collaborators discovered a new signaling network and control mechanism that contributes to the hormonal regulation of breast cancer cell proliferation and cell death in response to estrogens,[8] [9] aromatase inhibitors, and antiestrogens[10] This signaling includes communication between the endoplasmic reticulum and mitochondria, and reflects novel interactions within the unfolded protein response. His group has also identified interferon regulatory factor-1 as a breast cancer suppressor gene,[11] [12] and worked on the development and application of genomic and novel bioinformatic methods in translational breast cancer studies [13] [14]

Aspects of Acquired Endocrine Resistance in Breast Cancer

Clarke identified some of the first non-nuclear activities of endocrine therapies including the effects of Tamoxifen and high dose estrogens on membrane fluidity.[15] In his studies regarding drug resistance and MDR1/P-glycoprotein,[16] he published the first statistical meta-analysis of the role of MDR1 in breast cancer,[17] and defined novel mechanisms of resistance to Taxanes.[18] [19] He was among the pioneers to implicate the unfolded protein response (UPR) in acquired endocrine resistance[9] [20] and in regulating involution in the normal mammary gland.[21] In addition, his research team was among the first to implicate key BCL2 family members, interferon regulatory factor-1 and NFκB in the endocrine resistant phenotype,[20] and to define basic interactions among the UPR, autophagy and apoptosis,[22] regulation of immune markers,[23] and the role for epigenetic changes in terms of determining trans-generational effects on endocrine responsiveness.[24]

In his studies on the endocrine-mediated regulation of breast cancer progression and cell fate, he explored the concept that the final cell-fate decision is based on integrated signaling that flows through the endoplasmic reticulum, mitochondria and nucleus. Together, this signaling is represented in a modular network that regulates and executes five key cell function modules (autophagy, cell death, metabolism, proliferation, and UPR).[8] [9] [25]

Awards and honors

Bibliography

Notes and References

  1. Web site: Robert Clarke, Ph.D., D.Sc..
  2. Web site: Robert Clarke. scholar.google.com.
  3. Endocrine resistance in breast cancer – an overview and update. Robert. Clarke. John J.. Tyson. J. Michael. Dixon. December 15, 2015. Molecular and Cellular Endocrinology. 418. 3. 220–234. 10.1016/j.mce.2015.09.035. 26455641. 4684757.
  4. Web site: Editorial Board | Cancer Research. cancerres.aacrjournals.org.
  5. Acquisition of hormone-independent growth in MCF-7 cells is accompanied by increased expression of estrogen-regulated genes but without detectable DNA amplifications. N.. Brünner. V.. Boulay. A.. Fojo. C. E.. Freter. M. E.. Lippman. R.. Clarke. January 15, 1993. Cancer Research. 53. 2. 283–290. PubMed. 8380254.
  6. MCF7/LCC2: a 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780. N.. Brünner. T. L.. Frandsen. C.. Holst-Hansen. M.. Bei. E. W.. Thompson. A. E.. Wakeling. M. E.. Lippman. R.. Clarke. July 15, 1993. Cancer Research. 53. 14. 3229–3232. PubMed. 8324732.
  7. MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance to the steroidal antiestrogen ICI 182,780 confers an early cross-resistance to the nonsteroidal antiestrogen tamoxifen. N.. Brünner. B.. Boysen. S.. Jirus. T. C.. Skaar. C.. Holst-Hansen. J.. Lippman. T.. Frandsen. M.. Spang-Thomsen. S. A.. Fuqua. R.. Clarke. August 15, 1997. Cancer Research. 57. 16. 3486–3493. PubMed. 9270017.
  8. Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells. John J.. Tyson. William T.. Baumann. Chun. Chen. Anael. Verdugo. Iman. Tavassoly. Yue. Wang. Louis M.. Weiner. Robert. Clarke. July 10, 2011. Nature Reviews Cancer. 11. 7. 523–532. 10.1038/nrc3081. 21677677. 3294292.
  9. Endoplasmic Reticulum Stress, the Unfolded Protein Response, Autophagy, and the Integrated Regulation of Breast Cancer Cell Fate. Robert. Clarke. Katherine L.. Cook. Rong. Hu. Caroline O. B.. Facey. Iman. Tavassoly. Jessica L.. Schwartz. William T.. Baumann. John J.. Tyson. Jianhua. Xuan. Yue. Wang. Anni. Wärri. Ayesha N.. Shajahan. March 15, 2012. Cancer Research. 72. 6. 1321–1331. 10.1158/0008-5472.CAN-11-3213. 22422988. 3313080.
  10. Disruption of estrogen receptor DNA-binding domain and related intramolecular communication restores tamoxifen sensitivity in resistant breast cancer. Li Hua. Wang. Xiao Yi. Yang. Xiaohu. Zhang. Ping. An. Han-Jong. Kim. Jiaqiang. Huang. Robert. Clarke. C. Kent. Osborne. John K.. Inman. Ettore. Appella. William L.. Farrar. December 10, 2006. Cancer Cell. 10. 6. 487–499. 10.1016/j.ccr.2006.09.015. 17157789. free.
  11. Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosis. Kerrie B.. Bouker. Todd C.. Skaar. Rebecca B.. Riggins. David S.. Harburger. David R.. Fernandez. Alan. Zwart. Antai. Wang. Robert. Clarke. September 10, 2005. Carcinogenesis. 26. 9. 1527–1535. 10.1093/carcin/bgi113. 15878912. free.
  12. The A4396G polymorphism in interferon regulatory factor 1 is frequently expressed in breast cancer cell lines. Kerrie B.. Bouker. Todd C.. Skaar. David S.. Harburger. Rebecca B.. Riggins. David R.. Fernandez. Alan. Zwart. Robert. Clarke. May 10, 2007. Cancer Genetics and Cytogenetics. 175. 1. 61–64. PubMed. 10.1016/j.cancergencyto.2006.12.008. 17498560.
  13. The properties of high-dimensional data spaces: implications for exploring gene and protein expression data. Robert. Clarke. Habtom W.. Ressom. Antai. Wang. Jianhua. Xuan. Minetta C.. Liu. Edmund A.. Gehan. Yue. Wang. January 10, 2008. Nature Reviews Cancer. 8. 1. 37–49. 10.1038/nrc2294. 18097463. 2238676.
  14. Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer. Ming. Fan. Pingping. Xia. Robert. Clarke. Yue. Wang. Lihua. Li. September 25, 2020. Nature Communications. 11. 1. 4861. 10.1038/s41467-020-18703-2. 32978398. 7519071. 2020NatCo..11.4861F. 10919/102232. free.
  15. Reduction of the membrane fluidity of human breast cancer cells by tamoxifen and 17 beta-estradiol. R.. Clarke. H. W.. van den Berg. R. F.. Murphy. November 7, 1990. Journal of the National Cancer Institute. 82. 21. 1702–1705. PubMed. 10.1093/jnci/82.21.1702. 2231758.
  16. Effect of P-glycoprotein expression on sensitivity to hormones in MCF-7 human breast cancer cells. R.. Clarke. S.. Currier. O.. Kaplan. E.. Lovelace. V.. Boulay. M. M.. Gottesman. R. B.. Dickson. October 7, 1992. Journal of the National Cancer Institute. 84. 19. 1506–1512. PubMed. 10.1093/jnci/84.19.1506. 1359153.
  17. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. B. J.. Trock. F.. Leonessa. R.. Clarke. July 2, 1997. Journal of the National Cancer Institute. 89. 13. 917–931. 10.1093/jnci/89.13.917. 9214671.
  18. Caveolin-1 Tyrosine Phosphorylation Enhances Paclitaxel-mediated Cytotoxicity. February 23, 2007. Journal of Biological Chemistry. 282. 8. 5934–5943. 10.1074/jbc.M608857200. free. Shajahan. Ayesha N.. Wang. Aifen. Decker. Markus. Minshall. Richard D.. Liu. Minetta C.. Clarke. Robert. 17190831.
  19. Tyrosine-phosphorylated Caveolin-1 (Tyr-14) Increases Sensitivity to Paclitaxel by Inhibiting BCL2 and BCLxL Proteins via c-Jun N-terminal Kinase (JNK). Ayesha N.. Shajahan. Zachary C.. Dobbin. F. Edward. Hickman. Sivanesan. Dakshanamurthy. Robert. Clarke. May 18, 2012. The Journal of Biological Chemistry. 287. 21. 17682–17692. 10.1074/jbc.M111.304022. 22433870. 3366801. free.
  20. Association of interferon regulatory factor-1, nucleophosmin, nuclear factor-kappaB, and cyclic AMP response element binding with acquired resistance to Faslodex (ICI 182,780). Gu. Z. Lee. Ry. Skaar. Tc. Bouker. Kb. Welch. Jn. Lu. J. Liu. A. Zhu. Y. Davis. N. Leonessa. F. Brünner. N. Wang. Y. Clarke. R. June 15, 2002. Cancer Research. 62. 12. 3428–3437. 12067985.
  21. Autophagy and unfolded protein response (UPR) regulate mammary gland involution by restraining apoptosis-driven irreversible changes. Anni. Wärri. Katherine L.. Cook. Rong. Hu. Lu. Jin. Alan. Zwart. David R.. Soto-Pantoja. Jie. Liu. Toren. Finkel. Robert. Clarke. October 15, 2018. Cell Death Discovery. 4. 1. 40. 10.1038/s41420-018-0105-y. 30345078. 6186758.
  22. Glucose-regulated protein 78 controls cross-talk between apoptosis and autophagy to determine antiestrogen responsiveness. Katherine L.. Cook. Ayesha N.. Shajahan. Anni. Wärri. Lu. Jin. Leena A.. Hilakivi-Clarke. Robert. Clarke. July 1, 2012. Cancer Research. 72. 13. 3337–3349. 10.1158/0008-5472.CAN-12-0269. 22752300. 3576872.
  23. Endoplasmic Reticulum Stress Protein GRP78 Modulates Lipid Metabolism to Control Drug Sensitivity and Antitumor Immunity in Breast Cancer. Katherine L.. Cook. David R.. Soto-Pantoja. Pamela A. G.. Clarke. M. Idalia. Cruz. Alan. Zwart. Anni. Wärri. Leena. Hilakivi-Clarke. David D.. Roberts. Robert. Clarke. October 1, 2016. Cancer Research. 76. 19. 5657–5670. 10.1158/0008-5472.CAN-15-2616. 27698188. 5117832.
  24. Effects of In Utero Exposure to Ethinyl Estradiol on Tamoxifen Resistance and Breast Cancer Recurrence in a Preclinical Model. Leena. Hilakivi-Clarke. Anni. Wärri. Kerrie B. Bouker. Xiyuan. Zhang. Katherine L. Cook. Lu. Jin. Alan. Zwart. Nguyen. Nguyen. Rong. Hu. M Idalia. Cruz. Sonia. de Assis. Xiao. Wang. Jason. Xuan. Yue. Wang. Bryan. Wehrenberg. Robert. Clarke. September 8, 2016. JNCI Journal of the National Cancer Institute. 109. 1. djw188. 10.1093/jnci/djw188. 27609189. 6255695.
  25. A systems biology approach to discovering pathway signaling dysregulation in metastasis. Robert. Clarke. Pavel. Kraikivski. Brandon C.. Jones. Catherine M.. Sevigny. Surojeet. Sengupta. Yue. Wang. September 10, 2020. Cancer and Metastasis Reviews. 39. 3. 903–918. 10.1007/s10555-020-09921-7. 32776157. 7487029.
  26. Web site: 2012-2013. www.sigmaxi.org.
  27. Web site: AAAS Announces Leading Scientists Elected as 2019 Fellows | American Association for the Advancement of Science. www.aaas.org.

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