Greg M. Thurber
FAX: (734) 763-0459
Quantitative Pharmacology, Molecular Imaging Agent Design, Predictive Pharmacokinetic and Pharmacodynamic (PK/PD) modeling, Peptide and Protein Engineering, Click Chemistry
|Ph.D.||Massachusetts Institute of Technology||Chemical Engineering||2008|
|B.S.||Pennsylvania State University||
|University of Michigan
Chemical Engineering Department
Ann Arbor, MI
Assistant Professor, 2012 - present
Harvard Medical School/Massachusetts General Hospital
|Harvard Medical School/Massachusetts General Hospital
Center for Systems Biology
Postdoctoral Research Fellow, 2008-2011
Honors and Awards
|NIH Research Scientist Career Development Award (K01 Mechanism), 2011|
|Harvard Medical School NIH T32 Training Grant in Molecular Imaging, 2008-2011|
|Sigma Xi Scientific Research Society, Full Membership, 2008|
|Ludwig Fellowship in Cancer Research, MIT, 2006|
|Presidential Fellow, MIT, 2003|
|Chemical Engineering Student Marshall, Pennsylvania State University, 2003|
|1st place AIChE Regional Conference Paper Competition, 2003|
Molecular Imaging Agent Design – Significant advances have been made in understanding the molecular basis of many diseases including cancer, cardiovascular disease, autoimmune disorders, Alzheimer’s disease, and numerous others. Molecular imaging agents have the potential to translate this knowledge into making earlier and more accurate diagnoses and better monitoring of treatment outcomes. The broad research goal of the lab is to understand the transient distribution of imaging agents based on molecular properties (such as size, target affinity, lipophilicity, plasma clearance, etc.) in order to efficiently generate novel compounds. A mechanistic understanding of distribution also enables predictive scaling from animal models to the clinic for more efficient translation. Towards this goal, the lab uses a joint theoretical and experimental approach, applying fundamental chemical engineering principles, to utilize models while developing new imaging agents and measuring their properties and distribution.
Quantitative Pharmacology – Therapeutic molecules must reach their intended target for efficacy in disease treatment. Mathematical models developed for imaging agents also apply to therapeutic distribution, often delivered in a pseudo-steady state fashion (such as repeated oral dosing). Using sophisticated in vivo microscopy techniques and multi-scale mathematical modeling, the distribution of therapeutics is investigated from the organ level down to the tissue, cellular, and subcellular length scale. The results can be paired with pharmacodynamic studies to maximize therapeutic efficacy. Mathematical models developed from these experimental studies will become increasingly important as the distinction between small molecule drugs and macromolecule biologics decreases for many new therapeutics with novel properties.
19. Thurber, G.M., K.S. Yang, T. Reiner, R.H. Kohler, P. Sorger, T. Mitchison, and R. Weissleder. Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo. Nat Commun, 2013; 4: 1504.
18. Thurber, G.M.* and K.D. Wittrup, A mechanistic compartmental model for antibody uptake in tumors. J Theor Biol, 2012; 314: 57-68
* Denotes corresponding author
17. Feruglio P.F., C Vinegoni, L Fexon, G.M. Thurber, A Sbarbati, R Weissleder. Noise suppressed, multifocus image fusion for enhanced intraoperative navigation. J Biophotonics, 2012 DOI: 10.1002/jbio.201200086
16. Keliher, E.J., T Reiner, G.M. Thurber, R Upadhyay, R Weissleder. Efficient 18F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells. Chemistry Open, 2012 DOI: 10.1002/open.201200014
15. Devaraj NK*, G.M. Thurber*, E.J. Keliher, B. Marinelli, R. Weissleder. Reactive Polymer Enables Efficient In Vivo Bioorthogonal Chemistry. Proc Natl Acad Sci U S A, 2012; 109(13): 4762-7
* Denotes shared 1st authorship
14. Wittrup KD, G.M. Thurber, M.M. Schmidt, J.J. Rhoden. Practical Theoretic Guidance for the Design of Tumor Targeting Agents. Methods in Enzymology, 2012. 503: p. 255-268
13. Thurber*, G.M., Weissleder R*. A Systems Approach for Tumor Pharmacokinetics. PLoS ONE, 2011; 6(9): e24696.
* Denotes corresponding authors
12. Reiner T, G.M. Thurber, Gaglia J, et al. Measurement of Beta Cell Mass Using a Second-Generation Fluorescent Exendin-4 Analog. Proc Natl Acad Sci U S A, 2011; 108 (31): p. 12815-20.
11. Thurber G., Kinetics of Antibody Penetration into Tumors. In: Speer TW, editor. Targeted Radionuclide Therapy. Philadelphia: Lippincott Williams and Wilkins; 2011. p. 168-81.
10. Thurber, G.M. and R. Weissleder, Quantitating Antibody Uptake In Vivo: Conditional Dependence on Antigen Expression Levels. Molecular Imaging and Biology, 2011; 13 (4): p. 623
9. Thurber, G.M., J.L. Figueiredo, R. Weissleder. Detection Limits of Intraoperative Near Infrared Imaging for Tumor Resection. J Surg Oncol 2010; 102 (7): p. 758-64.
8. Thurber, G.M., J.L. Figueiredo, and R. Weissleder, Multicolor Fluorescent Intravital Live Microscopy (FILM) for Surgical Tumor Resection in a Mouse Xenograft Model. PlosONE, 2009. 4: p. 8053
7. Nahrendorf, M., P. Waterman, G.M. Thurber, K. Groves, M. Rajopadhye, P. Panizzi, B Marinelli, E. Aikawa, M.J. Pittet, F.K. Swirski, and R. Weissleder. Hybrid in vivo FMT-CT imaging of protease activity in atherosclerosis with customized nanosensors. Arteriosclerosis, Thrombosis, and Vascular Biology, 2009. 29: p. 1444-1451
6. Devaraj, N.K., E.J. Keliher, G.M. Thurber, M. Nahrendorf, and R. Weissleder, F-18 Labeled Nanoparticles for in vivo PET-CT Imaging. Bioconjugate Chemistry, 2009. 20: p. 397-401
5. Schmidt, M.M., G.M. Thurber, and K.D. Wittrup, Kinetics of Anti-Carcinoembryonic Antigen Antibody Internalization: Effects of Affinity, Bivalency, and Stability. Cancer Immunology and Immunotherapy, 2008. 57: p. 1879-1890.
4. Thurber, G.M., M.M. Schmidt, and K.D. Wittrup, Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Advanced Drug Delivery Reviews, 2008. 60: p. 1421-1434.
3. Thurber, G.M. and K.D. Wittrup, Quantitative Spatiotemporal Analysis of Antibody Fragment Diffusion and Endocytic Consumption in Tumor Spheroids. Cancer Research, 2008. 68: p. 3334-3341.
2. Thurber, G.M., M.M. Schmidt, and K.D. Wittrup, Factors Determining Antibody Distribution in Tumors. Trends in Pharmacological Sciences, 2008. 29(2): p. 57-61.
1. Thurber, G.M., S.C. Zajic, and K.D. Wittrup, Theoretic Criteria for Antibody Penetration into Solid Tumors and Micrometastases. Journal of Nuclear Medicine, 2007. 48(6): p. 995-999.