John A. Katzenellenbogen
Swanlund Chair
Professor of Chemistry
Affiliate of the Beckman Institute and
Department of Bioengineering
Professor John A. Katzenellenbogen attended Harvard University for his undergraduate and graduate work. He received his B.A. in 1966 and his Ph.D. in 1969, at which time he joined the faculty at Illinois. Professor Katzenellenbogen's research interests involve organic and inorganic chemistry, biochemistry, molecular biology, and radiochemistry.
Research
The action of steroid hormones is mediated by their binding to specific, high-affinity binding proteins that are found in target tissues only at very low concentrations and are a challenge to isolate and purify. We probe the molecular details of action of steroid hormones using chemical and spectroscopic tools and molecular biology to understand how these interesting proteins work and to develop novel medical diagnostic procedures. Many of our studies are done in collaboration with biologists.
Novel Ligands and Dendrimers.
Based on our models of receptor structure, we use organic synthesis and molecular biology to design ligands of novel structure and hormone-dendrimer conjugates in search of those having unusual biological activity and specificity. We co-engineer novel ligand-receptor pairs to obtain agents with unique, orthogonal specificity, useful in gene therapy and in separating genomic and non-genomic signaling pathways.
Receptor Structure and Protein Microarrays.
We develop novel spectroscopic methods to analyze receptor structure, conformation, and dynamics, and receptor-coregulator interactions, and how these are affected by ligand structure. We are using chemical and molecular biological methods to fabricate protein microarrays through which receptor ligand binding and coactivator interactions can be assayed in a quantitative and high throughput manner.
Combinatorial Chemistry.
Based on our analysis of the key structural features important for the receptor binding and activity of steroid hormones and anti-hormones, we have undertaken a combinatorial approach to discover novel non-steroidal hormonal agents. These compounds have important receptor subtype and tissue selectivity that could be useful for menopausal hormone replacement and breast and prostate cancer prevention and therapy.
Radiopharmaceuticals.
A novel approach to the diagnosis of breast and prostate cancer is the use of gamma- and positron-emitting steroids to label the receptors in these tumors. We are designing hormones labeled with the positron-emitting radionuclide fluorine-18. The designed steroids must maximize specific to nonspecific binding and control the level of metabolism. Also, because F-18 has a half-life of only 110 min, synthetic methods that are rapid, convenient, and efficient are required. We are also working to incorporate the radioactive metals technetium-99m and gallium-68 into structural mimics of steroids while maintaining high receptor binding and good bio-distribution properties.
Publications
"Estrogen Dendrimer Conjugates That Preferentially Activate Extranuclear, Nongenomic Versus Genomic Pathways of Estrogen Action," W. R. Harrington, S. H. Kim, C. C. Funk, Z. Madak-Erdogan, R. Schiff, J. A. Katzenellenbogen, and B. S. Katzenellenbogen, Mol. Endocrinol., 20, 491-502 (2006).
"Synthesis and Evaluation of Estrogen Receptor Ligands with Bridged Oxabicyclic Cores Containing a Diarylethylene Motif: Estrogen Antagonists of Unusual Structure," H. B. Zhou, J. S. Comninos, F. Stossi, B. S. Katzenellenbogen, and J. A. Katzenellenbogen, J. Med. Chem., 48, 7261-7274 (2005).
"Synthesis of an Estrogen Receptor β-Selective Radioligand: 5-[18F]fluoro-(2R,3S)-2,3-bis(4-Hydroxyphenyl)Pentanenitrile and Comparison of in vivo Distribution with 16α-[18F]fluoro-17β-estradiol. ," J. Yoo, C. S. Dence, T. L. Sharp, J. A. Katzenellenbogen, and M. J. Welch, J. Med. Chem., 48, 6366-6378 (2005).
"Indazole Estrogens: Highly Selective Ligands for the Estrogen Receptor Beta," M. De Angelis, F. Stossi, K. A. Carlson, B. S. Katzenellenbogen, and J. A. Katzenellenbogen, J. Med. Chem., 48, 1132-1144 (2005).
"Coactivator Proteins as Determinants of Estrogen Receptor Structure and Function: Spectroscopic Evidence for a Novel Coactivator-Stabilized Receptor Conformation," A. Tamrazi, K. E. Carlson, A. L. Rodriguez, and J. A. Katzenellenbogen, Mol. Endocrinol., 19, 1516-1528 (2005).
"A Proteomic Microarray Approach for Exploring Ligand-initiated Nuclear Hormone Receptor Pharmacology, Receptor Selectivity, and Heterodimer Functionality," S. H. Kim, A. Tamrazi, K. E. Carlson, J. A. Katzenellenbogen, Mol. Cell. Proteomics, 4, 267-77 (2005).
Awards
- RSC Centenary Lectureship, 2008
- Gustavus John Esselen Award for Chemistry in the Public Interest, 2008
- American Chemical Society E. B. Hershberg Award for Important Discoveries in Medicinally Active Products, 2007
- Roy O. Greep Lecture Award, Endocrine Society
- ACS Arthur C. Cope Scholar
- Aebersold Award, Society of Nuclear Medicine
- Fellow, American Academy of Arts & Sciences
- Fellow, American Association for the Advancement of Science
- Guggenheim Fellowhip
- Dreyfus Fellowship
- Alfred P. Sloan Fellowship
