Richard D. DiMarchi

Background:

• Group Vice President of Biotechnology at Lilly Research Labs, 2003
• Postdoctoral Associate, Rockefeller University, 1981
• American Chemical Society Innovation Award (Discovery of Lys-Pro insulin - Humalog)
• Florida Atlantic University Alumnus of the Year
• Distinguished Research Recognition at Nobel Forum (Stockholm, Sweden), "Lispro Insulin: A Basis for Improved Glucose Control and Disease Management"
• Founding Council Member of American Peptide Society

The scientific work from this group was central to the discovery and the commercial development of Humulin®, Humalog® Humatrope®, rGlucagon®, Xigris®, and Forteo®. Current scientific activities of the laboratory are focused on the relationship of protein structure & function, with a particular interest in novel methods of drug delivery.

Humalog represents the first biosynthetic hormone optimized by rDNA technology approved as a human medicine. It established the precedent that endogenous hormones were not optimized for use as drugs, and that through insightful structural modification a more efficacious and safer protein could be developed. The structural basis for the design of Humalog was derived from our previous on the structure and function study of IGF-1

The limited transport of proteins across biologic membranes constitutes a major impediment to the full utilization of macromolecules for medicinal purposes. It is our belief that similar molecular mechanisms are limiting the transport of these molecules. We are interested in finding common chemical approaches that might enhance oral bioavailability, transport across the blood-brain barrier, and penetration of macromolecules to intracellular sites. One aspect of investigation within the current research group is the exploration of non-natural amino acids as a means to further enhance the pharmacological properties of biosynthetic proteins. We are in the midst of exploring these chemical approaches in collaboration with academic, biotechnology, and pharmaceutical company collaborators.

Selected Publications:

"Insulin Analogues and their Potential in the Management of Diabetes Mellitus." with G.B. Bolli, G.D. Park, S. Pramming, and V.A. Koivisto. Diabetologia, 42, 1151-1167 (1999)

"Crystal Structure of the Obese Protein Leptin-E100." With F. Zhang et al. Nature, 387, 206-209 (1998).

"Prevention of Vascular and Neural Dysfunction in Diabetic Rats by C-peptide." with Y. Ido, Y. et al. Science, 277, 563-566 (1997).

"The Rapid Identification of HIV Protease Inhibitors Through the Synthesis and Screening of Defined Peptide Mixtures." with R.A. Owens, P.D. Gesellchen, B.J. Houchins. Biochem. Biophys. Res. Comm., 181, 402-408 (1991).

"Protection of Cattle Against Foot-and-Mouth Disease by a Synthetic Peptide". DiMarchi et al. Science, 232, 639-641 (1986)