Indiana University
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The Gill Center for Biomolecular Science

Richard D. DiMarchi | Faculty

Richard D. DiMarchiProfessor and Chair, Department of Chemistry

Office: Chemistry A508
TEL: 856-1840
Email: rdimarch@indiana.edu

DiMarchi Group Website

Education

  • Ph.D. at Indiana University, 1979
  • B.S. at Florida Atlantic University, 1974

Research

  • Biochemistry
  • Bioorganic Chemistry
  • Chemical Biology
  • Proteomics

Richard DiMarchi is the Linda & Jack Gill Chair in Biomolecular Sciences, Professor and 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.

Media Links

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Representative Publications.

  • B. Finan, T. Ma, N. Ottaway, T. D. Müller, K. M. Habegger, K. M. Heppner, H. Kirchner, J. Holland, J. Hembree, C. Raver, S. H. Lockie, D. L. Smiley, V. Gelfanov, B. Yang, S. Hofmann, D. Bruemmer, D. J. Drucker, P. T. Pfluger, D. Perez-Tilve, J. Gidda, L. Vignati, L. Zhang, J. B. Hauptman, M. Lau, M. Brecheisen, S. Uhles, W. Riboulet, E. Hainaut, E. Sebokova, K. Conde-Knape, A. Konkar, R. D. DiMarchi, M. H. Tschöp, Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans. Sci. Transl. Med. 5, 209ra151 (2013).Ward B., Ottaway N., Ma D., Gelfanov V., Perez-Tilve D., Tschöp M., and DiMarchi R. Structural Changes Associated with Peptide Lipidation Broaden Biological Function, (submitted, Nature Chemical Biology  April 2013).
  • Heppner K., Piechowski C., Müller A., Ottaway N., Sisley S., Smiley D., Habegger K., Pfluger P., DiMarchi R., Biebermann H., Tschöp M., Sandoval D., Perez-Tilve D. Both acyl and des-acyl ghrelin regulate adiposity and glucose metabolism via CNS ghrelin receptors, (submitted, Endocrinology March 2013).
  • Kuna R., Girada S., Asalla S., Vallentyne J., Patterson J., Smiley D., DiMarchi R., Mitra P. Glucagon-like Peptide1 Receptor Mediated Endosomal cAMP Generation Promotes Glucose Stimulated Insulin Secretion in Pancreatic beta Cells, (accepted, AJP-Endocrinology and Metabolism February 2013).
  • Muller T., Habegger, K., Chun-Xia Y., Meyer C., Finan B., Heppner K., Ottaway N, Woods, S., Hofmnann, S., Pfluger, P., Perez-Tilve., D., Seeley, R., DiMarchi, R. and Tschop, M. The orphan receptor GPR83 regulates systemic energy metabolism via ghrelin-dependent and -independent mechanisms,  Nature Methods (accepted, February 2013).
  • Campanello, G., Ma, Z., Grossoehme, N., Guerra, A., Ward, B., DiMarchi, R., Ye, Y., Dann C. and Giedroc, D. Allosteric Inhibition of a Zinc-Sensing Transcriptional Repressor: Insights into the Arsenic Repressor (ArsR) Family, J. Mol. Biol (2013) online http://dx.doi.org/10.1016/j.jmb.2013.01.018
  • Habegger, K., Stemmer, K., Cheng, C., Muller, T., Heppner K., Ottaway N, Holland, J., Hembree, J., Smiley, D., Gelfanov., V., Krishna, R., Arafat, A., Konkar, A., Belli, S., Kapps, M., Woods, S., Hofmnann, S., D’Alessio, D., Pfluger, P., Perez-Tilve., D., Seeley, R., Konishi, M., Itoh, N., Kharitonenkov, A., Spranger, J., DiMarchi, R. and Tschop, M., Fibroblast Growth Factor 21 Mediates Specific Glucagon Actions, Diabetes Hofmann SM, Woods SC, Sivertsen B, Holst B, Pfluger PT, Perez-Tilve D, Tschöp MH.Diabetes (2013) online http://diabetes.diabetesjournals.org/lookup/doi:10.2337/db12-1116
  • Patterson , J., Li, P., Day, J.W., Gelfanov, V. and DiMarchi, R. A Hydrophobic Site on the GLP-1 Extracellular Domain Orients the Peptide Ligand for Signal Transduction, Molecular Medicine (2013) online http://dx.doi.org.10.1016/j.molmet.2013.01.003
  • Finan, B., Yan, Y., Ottaway, N., Stemmer, K., Muller, T.D., Yi, C-X., Habegger, K., Schriever, S.C., Garcia-Caceres, C., Kabra, D.G., Hembree, J., Holland, J., Raver, C., Seeley, R.J., Han, W., Irmler, M., Beckers, J., de Angelis, M.H., Tiano, J.P., Mauvais-Jarvis, F., Rerez-Tilve, D., Pfluger, P., Zhang, L., Gelfanov, V., DiMarchi, R.D., and Tschoep, M.H. Targeted Estrogen Delivery Reverses the Metabolic Syndrome, Nature Medicine (2012) published online 11 November 2012; doi:10.1038/nm.3009.
  • Heppner KM, Chaudhary N, Müller TD, Kirchner H, Habegger KM, Ottaway N, Smiley DL, Dimarchi R, Hofmann SM, Woods SC, Sivertsen B, Holst B, Pfluger PT, Perez-Tilve D, Tschöp MH. Acylation Type Determines Ghrelin's Effects on Energy Homeostasis in Rodents, Endocrinology (2012), 153(10), 4687-95. Epub 2012 Aug 3.
  • Lockie SH, Heppner KM, Chaudhary N, Chabenne JR, Morgan DA, Veyrat-Durebex C, Ananthakrishnan G, Rohner-Jeanrenaud F, Drucker DJ, Dimarchi R, Rahmouni K, Oldfield BJ, Tschöp MH, Perez-Tilve D.Direct Control of Brown Adipose Tissue Thermogenesis by Central Nervous System Glucagon-Like Peptide-1 Receptor Signaling, Diabetes. (2012) Aug 28. [Epub ahead of print].
  • Tschöp MH, DiMarchi RD., Outstanding Scientific Achievement Award Lecture 2011: defeating diabesity: the case for personalized combinatorial therapies, Diabetes (2012), 61(6), 1309-14.
  • Day JW, Gelfanov VM, Smiley D, Carrington PE, Eiermann G, Chicchi G, Erion M, Gidda J, Thornberry NA, Tschöp M, Marsh DJ, SinhaRoy R, DiMarchi RD, Pocai A Optimization of Agonism at Glucagon and GLP-1 Receptors to Safely Maximize Weight Reduction in DIO-rodents, J. Peptide Science (2012) 98:443-50.
  • Müller TD, Sullivan LM, Habegger K, Yi CX, Kabra D, Grant E, Ottaway N, Krishna R, Holland J, Hembree J, Perez-Tilve D, Pfluger PT, DeGuzman MJ, Siladi ME, Kraynov VS, Axelrod DW, DiMarchi R, Pinkstaff JK, Tschöp MH., Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21, J Pept Sci. (2012), 18(6), 383-93.
  • Mu J., Pinkstaff J., Li Z., Skidmore L., Li N., Myler H., Dallas-Yang Q., Putnam A.M., Yao J., Bussell S., Wu M., Norman T.C., Rodriguez C.G., Kimmel B., Metzger J.M., Manibusan A., Lee D., Zaller D.M., Zhang B.B., DiMarchi R.D., Berger J.P., Axelrod D.W. FGF21 Analogs of Sustained Action Enabled by Orthogonal Biosynthesis Demonstrate Enhanced Antidiabetic Pharmacology in Rodents, Diabetes (2012), 61(2), 505-12.
  • Cho H., Daniel T., Buechler Y.J., Litzinger D.C., Maio Z., Putnam A.M., Kraynov V.S., Sim B.C., Bussell S., Javahishvili T., Kaphle S., Viramontes G., Ong M., Chu S., Becky G.C., Lieu R., Knudsen N., Castiglioni P., Norman T.C., Axelrod D.W., Hoffman A.R., Schultz P.G., DiMarchi R.D., Kimmel B.E. Optimized clinical performance of growth hormone with an expanded genetic code, Proc Natl Acad Sci U S A. (2011) 108(22) 9060-5.
  • Patterson , J., Day, J.W., Gelfanov, V. and DiMarchi, R. Functional association of the N-terminal residues with the central region in glucagon-related peptides, Journal of Peptide Science (2011) 17(10) 659-66.
  • Wiedmer, Petra, Strasser, Florian, Horvath, Tamas L., Blum, David, DiMarchi, Richard, Lutz, Thomas, Schurmann, Annette, Joost, Hans-Georg, Tschop, Matthias H., Tong, Jenny Ghrelin-induced hypothermia:  A Physiological Basis but No Clinical Risk Physiol. Behav. (2011) 105(1) 43-51.
  • Patterson,  J., Ottaway, N., Gelfanov, V., Smiley, D., Perez-Tilve, D., Pfluger, P., Tschöp, M. and DiMarchi, R. A Novel Human-Based Receptor Antagonist of Sustained Action Reveals Body Weight Control by Endogenous GLP-1, ACS Chemical Biology (2011), 6(2), 135-45.
  • Day, J., Li, P., Patterson, J., Chabenne, J., DiMarchi Chabenne, M., Gelfanov,. V., and DiMarchi, R. Charge Inversion at Position 68 of the Glucagon and Glucagon-like peptide-1 Receptors Supports Selectivity in Hormone Action, Peptides (2011), 17(3), 218-25.
  • Patterson, J., Day, J., Gelfanov, V., DiMarchi, R.. Functional Association of the N-Terminal Residues with the Central Region in Glucagon-Related Peptides, Journal of Peptide Science (2011), published online: 20 Jun 2011 doi: 10.1002/psc. 1385
  • Wiedmer, P., Strasser, F., Horvath, T. L., Blum, D., DiMarchi, R., Lutz, T., Schurmann, A., Joost, H.G., Tschop, M. H., Tong, J. Ghrelin-induced hypothermia:  A Physiological Basis but No Clinical Risk, Physiol. Behav. (2011) 105(1) 43-51.
  • De, A. and DiMarchi, R. Synthesis & Characterization of Ester-Based Prodrugs of Glucagon-Like Peptide 1, Peptide Science (2010) 94(4) 448-456
  • Perez-Tilve, D., Hofmann, S.M., Basford, J., Nogueiras, R., Pfluger, P.T., Patterson, J.T., Grant, E., Wilson-Perez, H.,  Granholm, N., Arnold, M.,  Trevasksi, J.L., Butler, A., Davidson, W.S., Woods, S.C., Benoit, S., Sleeman, M.W., DiMarchi, R.D., Hui D.Y., and Tschőp, M.H. Melanocortin signaling in the CNS directly regulates circulating cholesterol (2010) Nature Neuroscience 13, 877-882
  • Bohrer, B., Li, Y., Reilly, J., Clemmer, D., DiMarchi, R., Radivojac, P., Tang, H. and Arnold, R. Combinatorial Libraries of Synthetic Peptides as a Model for Shotgun Proteomics (2010)  Anal. Chem. 82, 6559-6568.
  • Chabenne, J., DiMarchi Chabenne, M., Gelfanov, V., and DiMarchi, R. Optimization of the Native Glucagon Sequence for Medicinal Purposes Journal of Diabetes Science and Technology (2010), 4(6), 1322-31.
  • Habegger, K., Heppner, K., Geary, N., Bartness, T., DiMarchi, R. and Tschöp, M. The Metabolic Actions of Glucagon Revisited Nature Reviews Endocrinology (2010), 6(12), 689-97.
  • Ward, W.K., Massoud, R. G., Szybala, C. J., Engle, J. M., Youssef, J. E., Carroll, J. M., Roberts, C. T., DiMarchi, R.D. In Vitro and in Vivo Evaluation of Native Glucagon and Glucagon Analog (MAR-D28 during Aging: Lack of Cytotoxicity and Preservation of Hyperglycemic Effect Journal of Diabetes Science and Technology (2010), 4(6), 1311-1321.
  • Heppner, K. M., Habegger, K. M., Day, J., Pfluger, P. T., Perez-Tilve, D., Ward, B., Gelfanov, V., Woods, S. C., DiMarchi, R., Tschop, M. Glucagon Regulation of Energy Metabolism Physiology & Behavior (2010), 100(5), 545-8.
  • "A new glucagon and GLP-1 co-agonist eliminates obesity in rodents." With J. Day et al. Nature (2008) (online).
  • Li, Pengyun; Rogers, Tanya; Smiley, David; DiMarchi, Richard D.; Zhang, Faming. Crystallization and preliminary X-ray analysis of anti-obesity peptide hormone   oxyntomodulin.  Protein & Peptide Letters  (2008), 15(2), 232-234.
  • De, Arnab; DiMarchi, Richard D. Investigation of the Feasibility of an Amide-based Prodrug Under Physiological Conditions. International Journal of Peptide Research and Therapeutics (2008), 14(3), 255-262.
  • Cantel, Sonia; Le Chevalier Isaad, Alexandra; Scrima, Mario; Levy, Jay J.; DiMarchi, Richard D.; Rovero, Paolo; Halperin, Jose A.; D'Ursi, Anna Maria; Papini, Anna Maria; Chorev, Michael. Synthesis and conformational analysis of a cyclic peptide obtained via i to i+4 intramolecular side-chain to side-chain azide-alkyne 1,3-dipolar cycloaddition. Journal of Organic Chemistry (2008), 73(15), 5663-5674.
  • Li, Pengyun; Rogers, Tanya; Smiley, David; DiMarchi, Richard D.; Zhang, Faming. Crystallization and preliminary X-ray analysis of anti-obesity peptide hormone oxyntomodulin.  Protein & Peptide Letters  (2008), 15(2), 232-234.
  • Kohn, W.D., Micanovic, R., Myers, S.L., Vick, A.M., Kahl, S., Zhang, L., Strifler, B., Li, S., Shang, S., Beals, J., Mayer, J.P. and DiMarchi, R.D.  pI-shifted Basal Insulin Analogs With Extended in vivo Time Action and Favorable Receptor Selectivity.  Peptides (2007) 28 935-948.
  • Rubén Nogueiras, Paul Pfluger, Sulay Tovar, Arnold Myrtha, Sharon Mitchell, Amanda    Morris, Diego Perez-Tilve, Maria J. Vázquez, Petra Wiedmer, Tamara R. Castañeda, Richard DiMarchi, Matthias Tschöp, Annette Schurmann, Hans-Georg Joost, Lynda M. Williams, Wolfgang Langhans, and Carlos Dieguez. Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology (2007) 148(1)  21-26.
  • Yan, Liang Zeng; Hsiung, Hansen M.; Heiman, Mark L.; Gadski, Robert A.; Emmerson,    Paul J.; Hertel, JeAnne; Flora, David; Edwards, Patrick; Smiley, Dave; Zhang, Lianshan; Husain, Saba; Kahl, Steven D.;DiMarchi, Richard D.; Mayer, John P. Structure-activity relationships of MSH derived melanocortin-4 receptor peptide agonists. Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates) (2007), 7(11),1052-1067.
  • Mayer, John P.; Zhang, Faming; DiMarchi, Richard D. Insulin structure and function. Biopolymers (2007), 88(5), 687-713.
  • "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).
  • Selected Distinguished Lectures and Recognitions (since 2005)

    2011   American Peptide Society Merrifield Award
    2011   Distinguished Faculty Research Lecturer, Indiana University
    2010   Co-organizer of Peptide Therapeutic Symposium, La Jolla, CA
    2010   Plenary Lecture European Peptide Society Symposia, Copenhagen
    2010   Plenary Lecture Keystone Symposia on Molecular and Cellular Biology, Whistler, B.C.
    2009   Watanabe Biotechnology Leadership Award – State of Indiana Biocrossroads Award
    2009   Keynote Lecturer 2009 Roche Peptide Symposium
    2009   Co-organizer 21st American Peptide Symposium
    2009   Co-organizer of International Symposium in Diabetes & Metabolism, India
    2007   Am. Chem. Soc. Carothers Award for Excellence in Industrial Chemistry, Wilmington
    2007   Honorary Doctorate, Valparasio University.
    2006   Am. Chem. Soc. Esselen Award for Outstanding Chemistry in Public Interest, Boston
    2006   Am. Chem. Soc. Barnes Award for Excellence in Chemical Research Management, Atlanta
    2005   Am. Assoc. Pharmaceutical Scientists Career Achievement Award in Biotecchnology
    2005   Purdue University, Andrew Mellon Named Lecture in Analytical Chemistry
    2005   Plenary Lecture AAPS “rDNA Optimization of Endocrine Hormones”, San Francisco

  • Patents 2010 – 2011

    DiMarchi, R. D.; Tao, M.  GIP mixed agonists for treatment of metabolic disorders and obesity.  (2010) International:  WO 2010/011439 A2 - PCT/US2009/047447

    DiMarchi, R. D.; Kou, B.  Amide Based Glucagon Superfamily Peptide Prodrugs.  (2010) International: WO 2010/071807 A1 – PCT/US2009/068745

    DiMarchi, R. D. Dipeptide Linked Medicinal Agents. (2010) International:  WO 2010/080605 A1 – PCT/US2009/068711

    DiMarchi, R. D.; Han, J.. Insulin Analogs. (2010) International: WO 2010/080606 A1 – PCT/US2009/068712

    DiMarchi, R. D.; Kou, B.; Han, J.; Cheng, S.  YL-Based Insulin-Like Growth Factors Exhibiting High Activity at the Insulin Receptor. (2010) International: WO 2010/080607 A1 – PCT/US2009/068713

    DiMarchi, R. D.; Kou, B.; Cheng, S. Amide-Based Insulin Prodrugs. (2010) International: WO 2010/080609 A1 – PCT/US2009/068716

    DiMarchi, R. D.; Pocai, A.; Santoprete, A.; Pessi, A.; Ward, B.; Marsh, D.; Capito, E.; Bianchi, E.; Eiermann, G.; Metzger, J.; Galinella, P.; Carrington, P.; Sinha Roy, R..  Oxyntomodulin Analogs. (2010) International:  WO 2010/096052 A1 – PCT/US2009/034448

    DiMarchi, R. D.; Pocai, A.; Santoprete, A.; Pessi, A.; Ward, B.; Marsh, D.; Capito, E.; Bianchi, E.; Eiermann, G.; Metzger, J.; Galinella, P.; Carrington, P.; Sinha Roy, R.  Oxyntomodulin Analogs. (2010) International:  WO 2010/096142 A1 – PCT/US2009/068678

    DiMarchi, R. D.; Ward, B.; Smiley, D.; Patterson, J.; Chabenne, J.; Tao, M.; DiMarchi, M.; Day, J. GIP Receptor-Active Glucagon Compounds. (2010) International:  WO 2010/148089 A1 – PCT/US2010/038825

    DiMarchi, R.D. Glucagon/GLP-1 Receptor Co-Agonists. (2011) International:  WO 2011/075393 A2 – PCT/US2010/059724

    DiMarchi, R.D.; Chabenne, J.; DiMarchi, M.  Glucagon Analogs Exhibiting Enhanced Solubility in Physiological PH Buffers. (2010) US 2010/0190699 A1

    DiMarchi, R.D.; Smiley, D.; Patterson, J.; Day, J.; Chabenne, J.; DiMarchi, M.  Glucagon/GLP-1 Receptor Co-Agonists. (2010) US 2010/0190701 A1

    DiMarchi, R. D.; De, A..  Ester-Based Peptide Prodrugs. (2010) US 2010/0331246 A1

    DiMarchi, R. D.; De, A..  Ester-Based Peptide Prodrugs. (2011) US 2011/0065633 A1

    DiMarchi, R. D.; Yang, B.; Ouyang, C. Compounds Exhibiting Glucagon Antagonist and GLP-1 Agonist Activity.  (2011) US 2011/0098217 A1

    DiMarchi, R. D.; Tao, M..  GIP-Based Mixed Agonists for Treatment of Metabolic Disorders and Obesity. (2011) US 2011/0166062 A1