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Robert Doyle

Robert Doyle


Laura J. and L. Douglas Meredith Professor - Director of Graduate Studies and Associate Chair - Department of Chemistry Syracuse University; Associate Professor of Medicine - SUNY, Upstate Medical University
Chemistry

rpdoyle@syr.edu

2-016B Center for Science and Technology
315.443.3584


Research Interests

I am a medicinal chemist with an interest in pharmaceutical drug development for the treatment of obesity and type 2 diabetes. I have a broad background in synthetic bioconjugate chemistry, drug delivery and protein biochemistry.

In 2005, I was appointed as an Assistant Professor of Chemistry at Syracuse University being subsequently promoted, with tenure, to Associate Professor in 2009 and then full Professor in 2014. In 2016, I was named the Laura J. and L. Douglas Meredith Professor. In 2011, I was appointed adjunct Associate Professor of Medicine at SUNY, Upstate Medical University (UMU), in the Department of Medicine. I am currently the Director of the Graduate Studies program, and Associate Chair, of the Department of Chemistry. As a PI, I have focused on the medicinal chemistry of vitamin B12 and its dietary pathway to modify drug pharmacodynamics and/or pharmacokinetics. Pursuant to this area, my group has worked to develop the synthetic chemistry of vitamin B12, develop new fluorescent- and radio-probes of vitamin B12 and vitamin B12-peptide conjugates and ascertain where vitamin B12 is actively trafficked and stored. Most recently, my group (in collaboration with that of Professor Matthew Hayes (University of Pennsylvania)) has developed a unique GLP1-R agonist tied to vitamin B12 devoid of hypophagia and nausea/malaise for the treatment of diabetes (see Mietlicki-Baase EG, Liberini CG, Workinger JL, Bonaccorso RL, Borner T, Reiner DJ, Koch-Laskowski K, McGrath LE, Lhamo R, Stein LM, De Jonghe BC, Holz GG, Roth CL, Doyle RP, Hayes MR. A vitamin B12 conjugate of exendin-4 improves glucose tolerance without associated nausea or hypophagia in rodents. Diabetes, obesity & metabolism, 2018, 20, 1223-1234)

I am also interested in the origins of drug toxicity as it pertains to lysosomal Saposin proteins (see Tinklepaugh J, Smith BM, Hanlon E, Zubieta C, Bou-Abdallah F, Doyle RP. Exploring the Multi-ligand Binding Specificity of Saposin B Reveals Two Binding Sites. ACS Omega. 2017; 2(10):7141-7145) and the development of new chimeric peptide drugs to treat co-morbid diabetes and obesity (see Chepurny OG, Bonaccorso RL, Leech CA, Wöllert T, Langford GM, Schwede F, Roth CL, Doyle RP, Holz GG. Chimeric peptide EP45 as a dual agonist at GLP-1 and NPY2R receptors. Scientific Reports. 2018; 8(1):3749).

Education and Employment

  • B.A., 1998, Trinity College, Dublin, Ireland
  • Ph.D., 2002, Trinity College, Dublin, Ireland
  • Postdoctoral Fellow, 2002-2003, Australian National University
  • Postdoctoral Fellow, 2003-2005, Yale University
  • Joined Syracuse University Faculty, August 2005
  • Tenure and promotion to Associate Professor 2010
  • Full Professor 2014
  • Laura J. and L. Douglas Meredith Professor 2016

Honors & Awards

  • Enterprise Ireland Fellowship, 1998
  • RSC Fellowship, 2002
  • Rudolph Anderson Foundation Fellowship, 2004
  • Ewing Marion Kauffman Foundation Award, 2008
  • ACS New Investigator Award, 2009
  • Tenure, February 2009
  • Faculty of 1000, Associate Member 2010
  • James K. Duah-Agyeman Award for Outstanding Faculty, 2011
  • Faculty Advisor of the Year, 2012
  • CNY College Educator of the Year, 2013
  • Promoted to Full Professor, 2014
  • Laura J. and L. Douglas Meredith Professor 2016
  • Raiziss Rounds- Invited lecture. Department of Biochemistry and Biophysics, University of Pennsylvania, Sept. 13th 2018

 

Courses and Symposia

  • CHE 103: Chemistry in the Modern World
  • CHE 106: General Chemistry
  • CHE 139: Honors General Chemistry
  • CHE 412/612: Metals in Medicine
  • CHE 422/622: Advanced Inorganic Laboratory
  • CHE 450: Independent Research
  • CHE 400/600: Chemical Biology
  • CHE 412/612: Metals in Biology & Medicine
  • Meredith Symposium in the Chemical and Biological Sciences

Research Focus

The Doyle group are medicinal chemists that focus on drug development, targeting and toxicity as well as target validation and platform technology development for pharmocokinetic and pharmacodynamic improvement of therapeutics.

We are interested in two main areas:

  1. Utilizing the vitamin B12 dietary pathway to improve drug delivery, impact drug pharmacokinetics and modify brain uptake and localization.

    As part of this project we also develop new peptide dual and tri-agonists of the appetite suppressing receptor NPY2-R along with the glucoregulatory receptor GLP1-R and Glugacon receptor to simultaneously treat obesity and diabetes.

  2. Exploring the implications of human lysosomal Saposin proteins on drug toxicity and conversely the effects of drug (e.g chloroquine; atovoquone) binding on Saposin dependent lipid hydrolysis and subsequent lipidosis.

Select Publications

A full list is available at http://www.ncbi.nlm.nih.gov/sites/myncbi/robert.doyle.1/bibliography/45718848/public/?sort=date&direction=ascending

See also: https://scholar.google.com/citations?hl=en&user=7G5ExC0AAAAJ

Mietlicki-Baase EG, Liberini CG, Workinger JL, Bonaccorso RL, Borner T, Reiner DJ, Koch-Laskowski K, McGrath LE, Lhamo R, Stein LM, De Jonghe BC, Holz GG, Roth CL, Doyle RP, Hayes MR. A vitamin B12 conjugate of exendin-4 improves glucose tolerance without associated nausea or hypophagia in rodents. Diabetes, obesity & metabolism, 2018, 20, 1223-1234.

Diabetes Obesity Metabolism cover

Chepurny OG, Bonaccorso RL, Leech CA, Wöllert T, Langford GM, Schwede F, Roth CL, Doyle RP, Holz GG. Chimeric peptide EP45 as a dual agonist at GLP-1 and NPY2R receptors. Scientific Reports. 2018; 8(1):3749.

Kuda-Wedagedara ANW, Workinger JL, Nexo E, Doyle RP, Viola-Villegas N. 89Zr-Cobalamin PET Tracer: Synthesis, Cellular Uptake, and Use for Tumor Imaging. ACS Omega. 2017; 2(10):6314-6320.

Tinklepaugh J, Smith BM, Hanlon E, Zubieta C, Bou-Abdallah F, Doyle RP. Exploring the Multi-ligand Binding Specificity of Saposin B Reveals Two Binding Sites. ACS Omega. 2017; 2(10):7141-7145.

Saposin B Binds the Lipofuscin Bisretinoid A2E and Prevents its Enzymatic and Photooxidation Doyle RP, Moody K, Nie Y, Bou-Abdallah F, Tinklepaugh J, Smith BM, Grown K. ChemPhotoChem. 2017, 1(6):256.

Chem Photo Chem cover

Roth CL, Doyle RP. Just a Gut Feeling: Central Nervous Effects of Peripheral Gastrointestinal Hormones. Endocrine development. 2017; 32:100-123.

Vitamin B12: Advances and Insights. Doyle RP and JL Workinger. Vitamin B12 and Drug Development; Chapter 14, p.338-364. (Obeid R, editor. US: CRC Press; 2017)

Vitamin B12 cover

Recent Patents

Filing Date [Technology] Internal Case Number Patent Title Application Type
2/3/2017 100905 Saposin B Binds the Lipofuscin Bisretinoid A2E and Prevents its Enzymatic and Photo Degradation PRV - Provisional
4/14/2017 100916 Peptide Drug Improvement Using Vitamin B12 and Haptocorrin Binding Substrate Conjugates PCT
6/6/2017 100876 Haptocorrin (R-Binder; Transcobalamin I) Substrates for the Oral Delivery of Vitamins or Minerals PCT
10/25/2017 100893 Assay for the Diagnosis of Macular Degeneration UTL - Utility
11/20/2017 100831 Improved Glycemic Control Using Intrinsic Factor Bound To A Vitamin B12 Conjugate of a Glucagon-Like Peptide-1 Receptor Agonist UTL - Utility
11/20/2017 100822 Compositions and Methods for Enhancing Peptide Stability Against Protease Digestion UTL - Utility

Links

Syracuse University Magazine Feature

Royal Society of Chemistry 2010 Emerging New Investigator

Group Journal covers

Undergraduate Research in the Doyle lab