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J. Oliver McIntyre, Ph.D.

Research Professor of Cancer Biology
Researcher

Contact Information:

Vanderbilt University Medical Center
771 Preston Building, 23rd & Pierce Avenues
Nashville, TN 37232-6840
615-936-2913
Fax: 615-936-2911

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.

Publications
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26096552.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26903264.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26791520.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25533764.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25732874.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25034624.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25500087.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24833491.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23750801.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20532643.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21857953.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20430759.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20135290.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19377965.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18465089.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18727087.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/19123982.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18787962.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18053410.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15652345.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15585619.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14556651.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14635184.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11237759.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11009606.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10098869.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8280053.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/7686368.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8383532.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/2742824.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/3355176.