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Chemistry A508
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Richard DiMarchi is the Linda & Jack Gill Chair in Biomolecular Sciences, Professor and a former Chairman of Chemistry at Indiana University. He is a retired Group Vice President at Eli Lilly & Company where for more than two decades he provided leadership in biotechnology, endocrine research and product development. He is a co-founder of Ambrx, Inc. and Marcadia Biotech. He serves as a board member to Ambrx, Marcadia, Isis Pharmaceuticals, and Alba Therapeutics. He is a scientific advisor to Epitome Biosciences, Kai Pharmaceuticals, Semafore Biotechnologies, and three venture funds; 5AM, TMP, and Twilight.

Professor DiMarchi is readily recognized for discovery and development of rDNA-derived Humalog® (LisPro-human insulin). This designer insulin represents the first demonstration that structurally altered rDNA-derived biosynthetic proteins can improve pharmacological performance without increasing the risk of an abnormal immunological response. As scientist and administrator Dr. DiMarchi also contributed to the commercial development of Humulin®, Humatrope®, Xigris®, rGlucagon®, Evista®, and Forteo®.

The goal of his current research and commercial endeavors is to develop proteins with enhanced therapeutic properties through biochemical optimization with non-natural amino acids, an approach he has termed chemical-biotechnology. He has published more than one hundred papers and he is co-inventor on ninety patents. He recently received the 2005 AAPS Career Research Achievement Award in Biotechnology, the 2006 ACS Earle B. Barnes Award for Leadership in Chemical Research Management, the 2006 ACS Gustavus Esselen Award for Chemistry in the Service of Public Interest, and the 2007 Wallace Carothers Award for Excellence in Polymer Sciences.

Research

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.

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)

Awards

• 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

Highlights

Richard DiMarchi is CICP's Innovator of the Year
The Central Indiana Corporate Partnership has named Indiana University Bloomington Chemistry Chair Richard DiMarchi its 2005 Innovator of the Year, an honor intended to recognize Indiana University scientists who have successfully transformed promising technologies into marketable products.  Full Story