James Oliver McIntyre, Ph.D.

Research Professor


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Faculty Appointments
Research Professor of Radiology and Radiological Sciences Research Professor of Cancer Biology
Ph.D., Vanderbilt University, Nashville, TennesseeM.A., University of Cambridge, Cambridge, United KingdomB.A., University of Cambridge, Cambridge, United Kingdom
Office Address
734 PRB
2220, Pierce Ave
Nashville, TN 37232-6840
Research Description
I am interested in translational preclinical research that aims to detect cancer, deliver targeted therapy and to monitor anti-tumor drug efficacy. For this work, we make use of a number of established mouse models of cancer to test a variety of customized activatable imaging and therapeutic agents, particularly novel compounds delivered with dendrimeric nanomaterials (NDs). We have developed 'proteolytic beacons' (PBs) that can be used to image the elevated activity of specific proteinases, e.g., the matrix metalloproteinases (MMPs), within the microenvironment of tumors .PBs exhibiting selectivity for different classes of MMPs have been used to image a number of pathologies including cancer, e.g., to selectively visualize tumors in various mouse models of colon, breast and lung cancers using either optical (fluorescent) or MRI contrast. We have developed a second generation of ND theranostic PBs designed to deliver activatable prodrugs to tumors. These prodrugs are being optimized to target delivery of cytotoxic drugs to tumors and enhance therapeutic efficacy while reducing systemic toxicity.
Research Keywords
Tumor imaging; Matrix metalloproteinases (MMPs); Proteolytic Beacons (PBs); In vivo molecular imaging of tumor-associated proteinases; Prodrugs; Theranostics; Mouse models of cancer.
Li H, Jiang X, Xie J, McIntyre JO, Gore JC, Xu J. Time-Dependent Influence of Cell Membrane Permeability on MR Diffusion Measurements. Magn Reson Med [print-electronic]. 2016 May; 75(5): 1927-34. PMID: 26096552, PMCID: PMC4676747, DOI: 10.1002/mrm.25724, ISSN: 1522-2594.

Haskett DG, Maestas D, Howerton SJ, Smith T, Ardila DC, Doetschman T, Utzinger U, McGrath D, McIntyre JO, Vande Geest JP. 2-Photon Characterization of Optical Proteolytic Beacons for Imaging Changes in Matrix-Metalloprotease Activity in a Mouse Model of Aneurysm. Microsc. Microanal [print-electronic]. 2016 Apr; 22(2): 349-60. PMID: 26903264, PMCID: PMC4823162, PII: S1431927616000088, DOI: 10.1017/S1431927616000088, ISSN: 1435-8115.

Sorace AG, Quarles CC, Whisenant JG, Hanker AB, McIntyre JO, Sanchez VM, Yankeelov TE. Trastuzumab improves tumor perfusion and vascular delivery of cytotoxic therapy in a murine model of HER2+ breast cancer: preliminary results. Breast Cancer Res. Treat [print-electronic]. 2016 Jan; 155(2): 273-84. PMID: 26791520, PMCID: PMC4833210, PII: 10.1007/s10549-016-3680-8, DOI: 10.1007/s10549-016-3680-8, ISSN: 1573-7217.

Samuelson LE, Scherer RL, VanSaun MN, Fan KH, Dozier EA, Carter KJ, Koyama T, Shyr Y, Aschner M, Stanwood GD, Bornhop DJ, Matrisian LM, McIntyre JO. New tools for the quantitative assessment of prodrug delivery and neurotoxicity. Neurotoxicology [print-electronic]. 2015 Mar; 47: 88-98. PMID: 25732874, PMCID: PMC4501381, PII: S0161-813X(15)00023-6, DOI: 10.1016/j.neuro.2015.02.005, ISSN: 1872-9711.

Felix DD, Gore JC, Yankeelov TE, Peterson TE, Barnes S, Whisenant J, Weis J, Shoukouhi S, Virostko J, Nickels M, McIntyre JO, Sanders M, Abramson V, Tantawy MN. Detection of breast cancer microcalcification using (99m)Tc-MDP SPECT or Osteosense 750EX FMT imaging. Nucl. Med. Biol [print-electronic]. 2015 Mar; 42(3): 269-73. PMID: 25533764, PMCID: PMC4889014, PII: S0969-8051(14)00549-6, DOI: 10.1016/j.nucmedbio.2014.11.010, ISSN: 1872-9614.

Whisenant JG, McIntyre JO, Peterson TE, Kang H, Sánchez V, Manning HC, Arteaga CL, Yankeelov TE. Utility of [18¿F]FLT-PET to assess treatment response in trastuzumab-resistant and trastuzumab-sensitive HER2-overexpressing human breast cancer xenografts. Mol Imaging Biol. 2015 Feb; 17(1): 119-28. PMID: 25034624, PMCID: PMC4311727, DOI: 10.1007/s11307-014-0770-z, ISSN: 1860-2002.

Whisenant JG, Sorace AG, McIntyre JO, Kang H, Sánchez V, Loveless ME, Yankeelov TE. Evaluating treatment response using DW-MRI and DCE-MRI in trastuzumab responsive and resistant HER2-overexpressing human breast cancer xenografts. Transl Oncol. 2014 Dec; 7(6): 768-79. PMID: 25500087, PMCID: PMC4311041, PII: S1936-5233(14)00104-1, DOI: 10.1016/j.tranon.2014.09.011, ISSN: 1936-5233.

Wilson GH, Gore JC, Yankeelov TE, Barnes S, Peterson TE, True JM, Shokouhi S, McIntyre JO, Sanders M, Abramson V, Ngyuen TQ, Mahadevan-Jansen A, Tantawy MN. An Approach to Breast Cancer Diagnosis via PET Imaging of Microcalcifications Using (18)F-NaF. J. Nucl. Med [print-electronic]. 2014 Jul; 55(7): 1138-43. PMID: 24833491, PMCID: PMC4320039, PII: jnumed.114.139170, DOI: 10.2967/jnumed.114.139170, ISSN: 1535-5667.

Samuelson LE, Scherer RL, Matrisian LM, McIntyre JO, Bornhop DJ. Synthesis and in vitro efficacy of MMP9-activated NanoDendrons. Mol. Pharm [print-electronic]. 2013 Aug 8/5/2013; 10(8): 3164-74. PMID: 23750801, PMCID: PMC4824186, DOI: 10.1021/mp4002206, ISSN: 1543-8392.

Guo N, Xie J, Manning HC, Deane NG, Ansari MS, Coffey RJ, Gore J, Price RR, Baldwin RM, McIntyre JO. A novel in vitro assay to assess phosphorylation of 3'-[(18)F]fluoro-3'-deoxythymidine. Mol Imaging Biol. 2011 Apr; 13(2): 257-64. PMID: 20532643, PMCID: PMC4180216, DOI: 10.1007/s11307-010-0351-8, ISSN: 1860-2002.

Gorden DL, Ivanova PT, Myers DS, McIntyre JO, VanSaun MN, Wright JK, Matrisian LM, Brown HA. Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model. PLoS ONE [print-electronic]. 2011; 6(8): e22775. PMID: 21857953, PMCID: PMC3153459, PII: PONE-D-11-04361, DOI: 10.1371/journal.pone.0022775, ISSN: 1932-6203.

Uddin MJ, Crews BC, Blobaum AL, Kingsley PJ, Gorden DL, McIntyre JO, Matrisian LM, Subbaramaiah K, Dannenberg AJ, Piston DW, Marnett LJ. Selective visualization of cyclooxygenase-2 in inflammation and cancer by targeted fluorescent imaging agents. Cancer Res. 2010 May 5/1/2010; 70(9): 3618-27. PMID: 20430759, PMCID: PMC2864539, PII: 70/9/3618, DOI: 10.1158/0008-5472.CAN-09-2664, ISSN: 1538-7445.

McIntyre JO, Scherer RL, Matrisian LM. Near-infrared optical proteolytic beacons for in vivo imaging of matrix metalloproteinase activity. Methods Mol. Biol. 2010; 622: 279-304. PMID: 20135290, PMCID: PMC4495730, DOI: 10.1007/978-1-60327-299-5_18, ISSN: 1940-6029.

McIntyre JO, Matrisian LM. Optical proteolytic beacons for in vivo detection of matrix metalloproteinase activity. Methods Mol. Biol. 2009; 539: 155-74. PMID: 19377965, DOI: 10.1007/978-1-60327-003-8_9, ISSN: 1064-3745.

Scherer RL, McIntyre JO, Matrisian LM. Imaging matrix metalloproteinases in cancer. Cancer Metastasis Rev. 2008 Dec; 27(4): 679-90. PMID: 18465089, DOI: 10.1007/s10555-008-9152-9, ISSN: 0167-7659.

Quarles CC, Lepage M, Gorden DL, Fingleton B, Yankeelov TE, Price RR, Matrisian LM, Gore JC, McIntyre JO. Functional colonography of Min mice using dark lumen dynamic contrast-enhanced MRI. Magn Reson Med. 2008 Sep; 60(3): 718-26. PMID: 18727087, PMCID: PMC2646120, DOI: 10.1002/mrm.21724, ISSN: 1522-2594.

Scherer RL, VanSaun MN, McIntyre JO, Matrisian LM. Optical imaging of matrix metalloproteinase-7 activity in vivo using a proteolytic nanobeacon. Mol Imaging. 2008 May; 7(3): 118-31. PMID: 19123982, PMCID: PMC2777890, ISSN: 1535-3508.

Martin MD, Fingleton B, Lynch CC, Wells S, McIntyre JO, Piston DW, Matrisian LM. Establishment and quantitative imaging of a 3D lung organotypic model of mammary tumor outgrowth. Clin. Exp. Metastasis [print-electronic]. 2008; 25(8): 877-85. PMID: 18787962, PMCID: PMC2588650, DOI: 10.1007/s10585-008-9206-y, ISSN: 1573-7276.

Lepage M, Dow WC, Melchior M, You Y, Fingleton B, Quarles CC, Pépin C, Gore JC, Matrisian LM, McIntyre JO. Noninvasive detection of matrix metalloproteinase activity in vivo using a novel magnetic resonance imaging contrast agent with a solubility switch. Mol Imaging. 2007 Nov; 6(6): 393-403. PMID: 18053410, ISSN: 1535-3508.

Harrell PC, McCawley LJ, Fingleton B, McIntyre JO, Matrisian LM. Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells. Exp. Cell Res [print-electronic]. 2005 Feb 2/15/2005; 303(2): 308-20. PMID: 15652345, PII: S0014-4827(04)00574-9, DOI: 10.1016/j.yexcr.2004.09.020, ISSN: 0014-4827.

Fingleton B, Menon R, Carter KJ, Overstreet PD, Hachey DL, Matrisian LM, McIntyre JO. Proteinase activity in human and murine saliva as a biomarker for proteinase inhibitor efficacy. Clin. Cancer Res. 2004 Dec 12/1/2004; 10(23): 7865-74. PMID: 15585619, PII: 10/23/7865, DOI: 10.1158/1078-0432.CCR-04-1252, ISSN: 1078-0432.

McIntyre JO, Fingleton B, Wells KS, Piston DW, Lynch CC, Gautam S, Matrisian LM. Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. Biochem. J. 2004 Feb 2/1/2004; 377(Pt 3): 617-28. PMID: 14556651, PMCID: PMC1223892, PII: BJ20030582, DOI: 10.1042/BJ20030582, ISSN: 1470-8728.

McIntyre JO, Matrisian LM. Molecular imaging of proteolytic activity in cancer. J. Cell. Biochem. 2003 Dec 12/15/2003; 90(6): 1087-97. PMID: 14635184, DOI: 10.1002/jcb.10713, ISSN: 0730-2312.

Jeyakumar LH, Ballester L, Cheng DS, McIntyre JO, Chang P, Olivey HE, Rollins-Smith L, Barnett JV, Murray K, Xin HB, Fleischer S. FKBP binding characteristics of cardiac microsomes from diverse vertebrates. Biochem. Biophys. Res. Commun. 2001 Mar 3/9/2001; 281(4): 979-86. PMID: 11237759, PII: S0006-291X(01)94444-4, DOI: 10.1006/bbrc.2001.4444, ISSN: 0006-291X.

Loeb-Hennard C, McIntyre JO. (R)-3-hydroxybutyrate dehydrogenase: selective phosphatidylcholine binding by the C-terminal domain. Biochemistry. 2000 Oct 10/3/2000; 39(39): 11928-38. PMID: 11009606, PII: bi000425y, ISSN: 0006-2960.

Picklo MJ, Amarnath V, McIntyre JO, Graham DG, Montine TJ. 4-Hydroxy-2(E)-nonenal inhibits CNS mitochondrial respiration at multiple sites. J. Neurochem. 1999 Apr; 72(4): 1617-24. PMID: 10098869, ISSN: 0022-3042.

Green, D., Marks, A.R., Fleischer, S., and McIntyre, J.O. Wild Type and Mutant Human Heart (R)-3- Hydroxybutyrate Dehydrogenase Expressed in Insect Cells. Biochemistry. 1996; 35: 8158-65.

Klein, K., Rudy, B., McIntyre, J.O., Fleischer, S., and Trommer, W.E. Specific Interaction of (R)-3-Hydroxybutyrate Dehydrogenase with Membrane Phosphatidylcholine as Studied by ESR Specroscopy in Oriented Phospholipid Multibilayers: Coenzyme Binding Enhances the Interaction with Phosphatidylcholine. Biochemistry. 1996; 35: 3044-9.

Dalton LA, McIntyre JO, Fleischer S. Effect of selective thiol-group derivatization on enzyme kinetics of (R)-3-hydroxybutyrate dehydrogenase. Biochem. J. 1993 Dec 12/15/1993; 296 ( Pt 3): 563-9. PMID: 8280053, PMCID: PMC1137735, ISSN: 0264-6021.

Adami P, Duncan TM, McIntyre JO, Carter CE, Fu C, Melin M, Latruffe N, Fleischer S. Monoclonal antibodies for structure-function studies of (R)-3-hydroxybutyrate dehydrogenase, a lipid-dependent membrane-bound enzyme. Biochem. J. 1993 Jun 6/15/1993; 292 ( Pt 3): 863-72. PMID: 7686368, PMCID: PMC1134194, ISSN: 0264-6021.

Fleischer B, McIntyre JO, Kempner ES. Target sizes of galactosyltransferase, sialyltransferase, and uridine diphosphatase in Golgi apparatus of rat liver. Biochemistry. 1993 Mar 3/2/1993; 32(8): 2076-81. PMID: 8383532, ISSN: 0006-2960.

Cortese JD, McIntyre JO, Duncan TM, Fleischer S. Cooperativity in lipid activation of 3-hydroxybutyrate dehydrogenase: role of lecithin as an essential allosteric activator. Biochemistry. 1989 Apr 4/4/1989; 28(7): 3000-8. PMID: 2742824, ISSN: 0006-2960.

McIntyre JO, Latruffe N, Brenner SC, Fleischer S. Comparison of 3-hydroxybutyrate dehydrogenase from bovine heart and rat liver mitochondria. Arch. Biochem. Biophys. 1988 Apr; 262(1): 85-98. PMID: 3355176, PII: 0003-9861(88)90171-3, ISSN: 0003-9861.