John Katzenellenbogen Explained

John Albert Katzenellenbogen (born May 10, 1944) is an American Professor of Chemistry at the University of Illinois at Urbana-Champaign. He studies the development of novel agents for the treatment of hormone-responsive and non-responsive breast and prostate cancers and the design of estrogens and antiestrogens that have a favorable balance of beneficial versus detrimental effects.[1]

Early life

John Katzenellenbogen was born May 10, 1944, in Poughkeepsie, New York. His parents taught at Vassar College, his father a professor of art history and his mother a pianist. In 1958, his family moved to Baltimore, Maryland, where his father became Head of the Department of Art History at Johns Hopkins University[2] and his mother joined the faculty at Peabody Conservatory[3] and Goucher College.[4] He began playing the cello at age 10. Katzenellenbogen attended Gilman School[5] and held various summer jobs: in 1960, he worked at the Research Institute for Advanced Studies in the photosynthesis lab of Dr. Bessel Kok,[6] and, in 1961, he was a General Electric Student Research Fellow at Union College in Schenectady, New York. As an undergraduate at Harvard, he majored in chemistry, going on to complete a PhD in chemistry in 1969 at Harvard under the direction of Dr. E. J. Corey.[7]

Career

Katzenellenbogen began his academic career as an Assistant Professor of Chemistry at the University of Illinois at Urbana-Champaign[8] in 1969 and was promoted to Associate Professor in 1975 and to Full Professor in 1979. He was named the Roger Adams Professor and subsequently the chaired Swanlund Professor of Chemistry. He was one of the first academic chemists to work in the field of chemical biology. His major research efforts have focused on the study of steroid hormones and their biological receptors, the estrogen receptor in particular.

Katzenellenbogen's research is highly collaborative, and he works with other scientists locally, nationally, and internationally. He has published more than 550 articles[9] and has trained over 130 PhD's and Postdoctoral Associates. He is a member of the American Association for the Advancement of Science and a fellow of the American Academy of Arts and Sciences, on whose National Council he served for many years. He has received numerous awards from scientific societies, including the Arthur C. Cope Scholar Award,[10] the E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances from the American Chemical Society,[11] the Endocrine Society's Fred Conrad Koch Lifetime Achievement Award,[12] which he shared with Dr. Benita Katzenellenbogen, and the Award for Outstanding Achievements in Chemistry in Cancer Research from the American Association for Cancer Research In 2018, Katzenellenbogen was inducted into the Medicinal Chemistry Hall of Fame of the American Chemical Society.

Research

Katzenellenbogen developed the first affinity label for the estrogen receptor that was widely used to characterize its physical and biochemical properties,[13] [14] and he elucidated the metabolic activation of antiestrogens and characterized their sites of action.[15] He also pioneered the development of positron emission tomography (PET) imaging agents for estrogen, androgen, and progesterone receptors.[16] [17] [18] [19] The PET imaging agents he developed, FES,[20] FDHT,[21] and FFNP,[22] continue to be utilized to improve the prediction of patient response to endocrine therapy agents and to assist in the development of new cancer therapeutics. His more recent work is focused on developing novel antiestrogens effective against endocrine therapy-resistant forms of breast cancer[23] [24] and dissecting the mechanisms and signaling pathways that underlie the selective actions of estrogens in different target tissues.[25] [26] [27] [28]

Notes and References

  1. Web site: John Katzenellenbogen . illinois.edu . December 5, 2017.
  2. News: Dr. Adolf Katzenellenbogen, Johns Hopkins Professor, Dies. 1964-10-01. The New York Times. 2017-11-23. en-US. 0362-4331.
  3. Web site: Scott Foglesong SFCM. sfcm.edu. 2017-11-23.
  4. 1970. Members of the Society. 40376030. College Music Symposium. 10. 182.
  5. News: Fall 2015 Gilman Bulletin. issuu. 2017-11-23. en.
  6. Web site: Notes: Elias James Corey. www.hcs.harvard.edu. 2017-11-23.
  7. Web site: Group Members: Elias James Corey. www.hcs.harvard.edu. 2017-11-23. 2021-04-22. https://web.archive.org/web/20210422125331/http://www.hcs.harvard.edu/coreylab/members/members.php. dead.
  8. Web site: John A. Katzenellenbogen Chemistry at Illinois. chemistry.illinois.edu. en. 2017-11-22.
  9. Web site: Katzenellenbogen JA - PubMed - NCBI. pubmeddev. www.ncbi.nlm.nih.gov. 2017-11-22.
  10. Web site: Arthur C. Cope Scholar Awards - American Chemical Society. American Chemical Society. en. 2017-11-22.
  11. Web site: E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances - American Chemical Society. American Chemical Society. en. 2017-11-22.
  12. Web site: Katzenellenbogens Awarded Fred Conrad Koch Lifetime Achievement Award by the Endocrine Society Chemistry at Illinois. chemistry.illinois.edu. en. 2017-11-22.
  13. Harlow. K. W.. Smith. D. N.. Katzenellenbogen. J. A.. Greene. G. L.. Katzenellenbogen. B. S.. 1989-10-15. Identification of cysteine 530 as the covalent attachment site of an affinity-labeling estrogen (ketononestrol aziridine) and antiestrogen (tamoxifen aziridine) in the human estrogen receptor. The Journal of Biological Chemistry. 264. 29. 17476–17485. 10.1016/S0021-9258(18)71519-6. 0021-9258. 2793867. free.
  14. Robertson. D. W.. Wei. L. L.. Hayes. J. R.. Carlson. K. E.. Katzenellenbogen. J. A.. Katzenellenbogen. B. S.. October 1981. Tamoxifen aziridines: effective inactivators of the estrogen receptor. Endocrinology. 109. 4. 1298–1300. 10.1210/endo-109-4-1298. 0013-7227. 7285873.
  15. Robertson. D. W.. Katzenellenbogen. J. A.. Long. D. J.. Rorke. E. A.. Katzenellenbogen. B. S.. January 1982. Tamoxifen antiestrogens. A comparison of the activity, pharmacokinetics, and metabolic activation of the cis and trans isomers of tamoxifen. Journal of Steroid Biochemistry. 16. 1. 1–13. 0022-4731. 7062732. 10.1016/0022-4731(82)90137-6.
  16. Katzenellenbogen. J. A.. Welch. M. J.. Dehdashti. F.. May 1997. The development of estrogen and progestin radiopharmaceuticals for imaging breast cancer. Anticancer Research. 17. 3B. 1573–1576. 0250-7005. 9179196.
  17. Mortimer. J. E.. Dehdashti. F.. Siegel. B. A.. Trinkaus. K.. Katzenellenbogen. J. A.. Welch. M. J.. 2001-06-01. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. Journal of Clinical Oncology. 19. 11. 2797–2803. 10.1200/JCO.2001.19.11.2797. 0732-183X. 11387350.
  18. Dehdashti. Farrokh. Picus. Joel. Michalski. Jeff M.. Dence. Carmen S.. Siegel. Barry A.. Katzenellenbogen. John A.. Welch. Michael J.. March 2005. Positron tomographic assessment of androgen receptors in prostatic carcinoma. European Journal of Nuclear Medicine and Molecular Imaging. 32. 3. 344–350. 10.1007/s00259-005-1764-5. 1619-7070. 15726353. 24329403.
  19. Dehdashti. Farrokh. Mortimer. Joanne E.. Trinkaus. Kathryn. Naughton. Michael J.. Ellis. Matthew. Katzenellenbogen. John A.. Welch. Michael J.. Siegel. Barry A.. February 2009. PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Research and Treatment. 113. 3. 509–517. 10.1007/s10549-008-9953-0. 1573-7217. 3883567. 18327670.
  20. Kiesewetter. D. O.. Kilbourn. M. R.. Landvatter. S. W.. Heiman. D. F.. Katzenellenbogen. J. A.. Welch. M. J.. November 1984. Preparation of four fluorine- 18-labeled estrogens and their selective uptakes in target tissues of immature rats. Journal of Nuclear Medicine. 25. 11. 1212–1221. 0161-5505. 6092569.
  21. Liu. A.. Carlson. K. E.. Katzenellenbogen. J. A.. 1992-05-29. Synthesis of high affinity fluorine-substituted ligands for the androgen receptor. Potential agents for imaging prostatic cancer by positron emission tomography. Journal of Medicinal Chemistry. 35. 11. 2113–2129. 0022-2623. 1597861. 10.1021/jm00089a024.
  22. Kochanny. M. J.. VanBrocklin. H. F.. Kym. P. R.. Carlson. K. E.. O'Neil. J. P.. Bonasera. T. A.. Welch. M. J.. Katzenellenbogen. J. A.. 1993-04-30. Fluorine-18-labeled progestin ketals: synthesis and target tissue uptake selectivity of potential imaging agents for receptor-positive breast tumors. Journal of Medicinal Chemistry. 36. 9. 1120–1127. 0022-2623. 8487253. 10.1021/jm00061a002.
  23. Min. Jian. Guillen. Valeria Sanabria. Sharma. Abhishek. Zhao. Yuechao. Ziegler. Yvonne. Gong. Ping. Mayne. Christopher G.. Srinivasan. Sathish. Kim. Sung Hoon. 2017-07-27. Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor Mediated Activities in Breast Cancer Cells. Journal of Medicinal Chemistry. 60. 14. 6321–6336. 10.1021/acs.jmedchem.7b00585. 1520-4804. 28657320. 6039301.
  24. Zhao. Yuechao. Laws. Mary J.. Guillen. Valeria Sanabria. Ziegler. Yvonne. Min. Jian. Sharma. Abhishek. Kim. Sung Hoon. Chu. David. Park. Ben Ho. 2017-10-15. Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors. Cancer Research. 77. 20. 5602–5613. 10.1158/0008-5472.CAN-17-1265. 1538-7445. 5645250. 28904064.
  25. Madak-Erdogan. Zeynep. Kim. Sung Hoon. Gong. Ping. Zhao. Yiru C.. Zhang. Hui. Chambliss. Ken L.. Carlson. Kathryn E.. Mayne. Christopher G.. Shaul. Philip W.. 2016-05-24. Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues. Science Signaling. 9. 429. ra53. 10.1126/scisignal.aad8170. 1937-9145. 4896643. 27221711.
  26. Zhao. Yuechao. Gong. Ping. Chen. Yiru. Nwachukwu. Jerome C.. Srinivasan. Sathish. Ko. CheMyong. Bagchi. Milan K.. Taylor. Robert N.. Korach. Kenneth S.. 2015-01-21. Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis. Science Translational Medicine. 7. 271. 271ra9. 10.1126/scitranslmed.3010626. 1946-6242. 4790140. 25609169.
  27. Saijo. Kaoru. Collier. Jana G.. Li. Andrew C.. Katzenellenbogen. John A.. Glass. Christopher K.. 2011-05-13. An ADIOL-ERβ-CtBP transrepression pathway negatively regulates microglia-mediated inflammation. Cell. 145. 4. 584–595. 10.1016/j.cell.2011.03.050. 1097-4172. 3433492. 21565615.
  28. Moore. Spencer M.. Khalaj. Anna J.. Kumar. Shalini. Winchester. Zachary. Yoon. JaeHee. Yoo. Timothy. Martinez-Torres. Leonardo. Yasui. Norio. Katzenellenbogen. John A.. 2014-12-16. Multiple functional therapeutic effects of the estrogen receptor β agonist indazole-Cl in a mouse model of multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America. 111. 50. 18061–18066. 10.1073/pnas.1411294111. 1091-6490. 4273334. 25453074. 2014PNAS..11118061M. free.

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