John A. Katzenellenbogen
Professor John A. Katzenellenbogen received his B.A. and Ph.D. from Harvard University and then joined the faculty at Illinois. His research interests involve organic and inorganic chemistry, biochemistry, molecular biology, and radiochemistry, with applications in cancer medicine (especially breast and prostate cancers), endocrine disorders, and neurological diseases (especially multiple sclerosis).
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.
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.
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.
Distinctions / Awards
- Medicinal Chemistry Hall of Fame, American Chemical Society, 2018
- Philip S. Portoghese Medicinal Chemistry Lectureship Awardee, American Chemical Society, 2010
- Fred Conrad Koch Lifetime Achievement Award from the Endocrine Society, 2016
- Outstanding Achievement in Chemistry in Cancer Research, American Association for Cancer Research, 2018
- Royal Society of Chemistry Centenary Lectureship, 2008
- The Presidents Award from the Society of Radiopharmaceutical Sciences, 2017
- Leading Edge in Basic Science Award from the Society for Toxicology, 2009
- Gustavus John Esselen Award for Chemistry in the Public Interest, American Chemical Society, 2008
- E. B. Hershberg Award for Important Discoveries in Medicinally Active Products, American Chemical Society, 2007