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Mark (Marty) Pagel

Honors

• Arizona Engineering Faculty Fellow, 2012
• Sydney E. Salmon Distinguished Junior Investigator Award, Arizona Cancer Center, Tucson, AZ, 2010
• Case School of Engineering Graduate Teaching Award, CWRU, Cleveland, OH, 2006
• Young Investigator Award, Contrast Media Research 2005 Symposium, 2005
• Early Career Recognition Award, Pharmacia Corp., St. Louis, MO, 2003
• John C. Sowden Prize in Chemistry, Washington University, St. Louis, MO, 1988

Education and Appointments

• B.A., Chemistry 1988, Washington University, St. Louis, MO
  
• B.A., Biology 1988, Washington University, St. Louis, MO
  
• PhD, Chemistry 1993, University of California, Berkeley CA
  

Research Interests

• Biochemistry
  
• Physical
  
• Bioanalytical
  
• Chemical Biology
  
• Spectroscopy/molecular Structure
  

Research Summary

Research Mission The Contrast Agent Molecular Engineering Laboratory (CAMEL) develops chemical agents that change the contrast of biomedical images. These contrast agents are designed to respond to molecular biomarkers of biological processes and pathologies. This molecular imformation is used to predict response to therapy before the therapy is applied, monitor the delivery of therapy to targeted tissues, and evaluate the early-stage effects of the therapy. These diagnostic methods that affect the choice of therapy are designed to provide personalized medicine for each individual patient.

CAMEL primarily focuses on the development of contrast agents for Magnetic Resonance Imaging (MRI). In particular, CAMEL has developed a new type of MRI contrast agent that can detect molecular biomarkers through Chemical Exchange Saturation Transfer (CEST). CAMEL has also developed CEST MRI methods for pre-clinical and clinical studies, and has also developed methods that rapidly synthesize CEST contrast agents. CAMEL also develops contrast agents for optical imaging, particularly focusing on applications of optical imaging that use multiple agents to inprove the specificity of molecular imaging. CAMEL is affiliated with the Department of Biomedical Engineering and the Biomedical Engineering Graduate Interdisciplinary Program, the Department of Chemistry and Biochemistry, the Department of Medical Imaging, the University of Arizona Cancer Center, and the Institute for Collaborative BioResearch (BIO5) at the University of Arizona in Tucson, AZ. These afiliations reflect the interdisciplinary resarch approach undertaken by CAMEL and the supportive environment for biomedical research at the University of Arizona.

Teaching Mission
CAMEL supports the teaching and training mission of the University of Arizona. The CAMEL laboratories provide an outstanding training environment for graduate and undergraduate students from a variety of disciplines, including biomedical engineering, chemistry & biochemistry, optical sciences, and computer science. In addition, Dr. Pagel regularly teaches a graduate-level course for biomedical engineers, BME 510: "Cell Biology for Engineers", which covers basic cell biology from a quantitative, design-driven perspetive. Dr. Pagel also teaches an undergraduate-level course for chemists and biochemists, CHEM 481: "Biophysical Chemistry" that covers quantum mehcanics and spectroscopy as applied to biochemistry and biotechnology. These multidisciplinary teaching roles further strengthen the teaching mission of CAMEL.

History
The concept of CAMEL was inspired by the Imaging in 2020 meeting held in 2001 at the Jackson Lake Lodge, Jackson, WY. This meeting facilitates open and effective communication among basic and clinical researchers from many interdisciplinary fields, and evaluates the opportunities and challenges for the development & clinical translation of molecular imaging by 2020 and beyond. CAMEL is founded on open communication and interdisciplinary research that leads to the development & clinical translation of molecular imaging.

CAMEL was first established in the Department of Biomedical Engineering at Case Western Reserve University in 2003. Dr. Marty Pagel started this research program after leaving the pharmaceutical industry to return to academia, to contribute to the high-risk high-reward field of molecular imaging. CAMEL pioneered the development of responsive CEST MRI contrast agents in 2003-2005, and demonstrated the first in vivo MRI studies with paramagnetic CEST agents in 2006-2007. CAMEL also developed new synthesis methods to create new types of MRI contrast agents. In 2008, Dr. Pagel moved CAMEL to the University of Arizona, in Tucson AZ. This transition provided CAMEL with resources and opportunities to collaborate with cancer biology researchers in the University of Arizona Cancer Center, and access to resources in the Departments of Biomedical Engineering, Chemistry & Biochemistry, and Medical Imaging. The combination of these diverse resources and multidisciplinary collaborators has been essential to the continued productivity of CAMEL. Furthermore, the collaborative research environment at the University of Arizona has greatly facilitated the expansion of CAMEL's resarch interests into optical imaging and clinical imaging. CAMEL has found an ideal home in the desert!

Selected Publications

1. Yoo B, Pagel MD. A facile synthesis of α-amino-DOTA as a versatile molecular imaging probe. Tetrahedron Lett, 2006, 47:7327-7330.

2. Yoo B, Pagel MD. A PARACEST MRI contrast agent to detect enzyme activity. J. Am. Chem. Soc., 2006, 128(43):14032-14033.

3. YooB, Pagel MD. Peptidyl Molecular Imaging Contrast Agents Using a New Solid Phase Peptide Synthesis Approach. Bioconj. Chem., 2007,18:903-911.

4. Yoo B, Raam M, Rosenblum R, Pagel MD. Enzyme-responsive PARACEST MRI contrast agents: A new biomedical imaging approach for studies of the proteasome. Contrast Media Molec. Imag., 2007, 2:189-198.

5. Liu G, Lu Y, Pagel MD. Design and characterization of new irreversible responsive PARACEST MRI contrast agent that detects nitric oxide. Magn. Reson. Med., 2007, 58:1249-1256.

6. Yoo B, Pagel MD. An overview of responsive MRI contrast agents for molecular imaging. Front. Bioscience, 2008, 13:1733-1752.

7. Sheth VR, van Heeckeren RC, Wilson AG, van Heeckeren AM, Pagel MD, Monitoring Infection and Inflammation in Murine Models of Cystic Fibrosis with Magnetic Resonance Imaging, J Magn Reson Imaging, 2008, 28(2):527-532.

8. Liu G, Ali, M, Yoo B, Griswold MA, Tkach JA, Pagel MD. PARACEST MRI With Improved Temporal Resolution. Magn Reson Med, 2009, 61:399-408.

9. Ali MM, Yoo B, Pagel MD. Tracking the relative in vivo pharmacokinetics of nanoparticles with PARACEST MRI. Molec Pharmaceutics, 2009, 6(5):1409-1416.

10. Yoo B, Sheth V, Pagel MD. An amine-derivatized, DOTA-loaded polymeric support for Fmoc Solid Phase Peptide Synthesis. Tet Lett, 2009, 50:4459-4462.

11. Ali MM, Liu G, Shah T, Flask CA, Pagel MD. Using Two Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agents for Molecular Imaging Studies. Acc Chem Res, 2009, 42(7):915-924.

12. Shah T, Lu L, Dell K, Pagel MD, Griswold M, Flask CA. CEST-FISP: A Novel Technique for Rapid Chemical Exchange Saturation Transfer (CEST) MRI at 7T. Magn Reson Med 2011, 65:432-437.

13. Li Y, Sheth VR, Liu G, Pagel MD. A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity. Contrast Media Molec. Imaging, 2011, 6(4):219-228.

14. Pagel MD. The hope and hype of multimodality imaging contrast agents. Nanomed., 2011, 6(6):945-948.

15. Pagel MD. Responsive paramagnetic chemical exchange saturation transfer MRI contrast agents. Imaging Med., 2011, 3(4):377-380.

16. Josan JS, De Silva CR, Yoo B, Lynch RM, Pagel MD, Vagner J, Hruby VJ. Fluorescent and lanthanide labeling for ligand screens, assays, and imaging. Methods Molecular Biol., 2011, 716:89-126.

17. Sheth VR, Li Y, Chen LQ, Howison CM, Flask CA, Pagel MD. Measuring in vivo tumor pHe with CEST-FISP MRI. Magn. Reson. Med., 2012, 67:760-768.

18. Liu G, Li Y, Sheth VR, Pagel MD. Imaging in vivo extracellular pH with a Single PARACEST MRI Contrast Agent. Molecular Imaging, 2012, 11(1):47-57.

19. Sheth VR, Liu G, Li Y, Pagel MD. Improved pH measurements with a single PARACEST MRI contrast agent. Contrast Media Molec. Imaging, 2012, 7:26-34.

20. Cárdenas-Rodríguez J, Li Y, Galons JP, Connell H, Pagel MD, Baker AF. Imaging biomarkers to monitor response to the hypoxia-activated prodrug TH-302 in the MiaPaCa2 flank xenograft model. Magn. Reson. Imaging, 2012, 30:1002-1009.

21. Ali MM, Bhuiyan MPI, Janic B, Varma NRS, Mikkelsen T, Ewing JR, Knight RA, Pagel MD, Arbab AS. A nano-sized PARACEST-fluorescence imaging contrast agent facilitates & validates in vivo CEST MRI detection of glioma. Nanomed., 2012, in press. Epub published 8/14/12.

22. Zhang X, Pagel MD, Baker AF, Gillies RJ. Reproducibility of MR perfusion imaging with Gd-DTPA and P792. Magn. Reson. Med., 2012, in press.

23. Stephen R, Pagel MD, Brown K, Baker AF, Meuillet EJ, Gillies RJ. Monitoring the development of xenograft triple negative breast cancer models using diffusion-weighted MRI. Exp. Biol. Med., 2012, in press.

24. Cárdenas-Rodríguez J, Howison CM, Pagel, MD. A linear algorithm of the reference region model for DCE-MRI is robust and relaxes requirements for temporal resolution. Magn. Reson. Med., 2012, in press.