Areas of Investigation
- When diseased, biological processes within the body are altered and serve as hallmarks of the disorder. These characteristics make it possible to develop agents for the detection of the molecular signatures of the disease and the establishment of next-generation therapeutic strategies. My laboratory has two main focuses - molecular imaging and targeted drug delivery - each of which works in concert with the other. With chemistry as the basis of our research program, we develop targeted nanoagents capable of the delivery of drug entities in a tissue- and cell-specific manner. This allows us to probe molecular pathways and tease out the causative factors involved in disease onset and progression, the data from which may allow for the establishment of novel therapeutic paradigms. At the same time, we also generate materials for the non-invasive readout of processes related to pathologies of interest. These molecular imaging agents are capable of monitoring therapeutic efficacy in vivo, allowing for serial imaging and the extraction of the maximum amount of information from each animal used. Our highly collaborative, multi-disciplinary projects run the gamut from cardiovascular disease to pulmonary fibrosis to bone regeneration, as the technologies at their heart are amenable to almost any biological question.
Lab focus
- The application of chemistry to biological problems
- Nanomedicine
- Targeted drug delivery
- Molecular imaging
Achievements
- Developed target-specific fluorescent imaging agents that allow for the identification of fibrin deposition which have found utility in cardiovascular, pulmonary, and orthopedic applications
- Generated platform technologies for the targeted delivery of small molecule drugs to specific cell types within diseased tissues, including myofibroblasts, cardiomyocytes, airway epithelium, and vascular endothelium.
- Created a novel near-infrared fluorogenic molecular probe of cytotoxic T lymphocyte activation capable of non-invasively reporting autoimmune activation, which is particularly useful in the examination of transplant rejection, as well as other disease including myocarditis.
Associate Professor of Cardiovascular Medicine, Masonic Medical Research Institute
Scientific Operations Manager, Masonic Medical Research Institute
Email – jmccarthy@mmri.edu, Phone – 315-624-7484
Dr. McCarthy began his career at Western New England College where he completed his B.S. in Chemistry in 1999. From there, he continued his studies at the University of Connecticut under the tutelage of Dr. Christian Brückner, focusing on the modification of porphyrinic chromophores. This work led to the discovery of previously unknown ring-fused chlorins and indaphyrins with unexpected photophysical properties. Upon the completion of his Ph.D. degree in Inorganic Chemistry in 2003, Dr. McCarthy joined the Center for Molecular Imaging Research at the Massachusetts General Hospital, under the direction of Dr. Ralph Weissleder, as a Ruth L. Kirschstein Institutional National Research Service Award T32 postdoctoral fellow. At the CMIR he was trained in nanomedicine and its application to biological systems, in addition to the molecular imaging that was the mainstay of the Center. In 2006, Dr. McCarthy was appointed as an Instructor in Radiology at Harvard Medical School and established his research group, which subsequently moved to the Center for Systems Biology at the MGH in 2007, where he was promoted to Assistant Professor of Radiology in 2010. Over the past decade the research focus of his group has become much more diverse, including the generation of imaging agents for the detection of molecular processes in the in vivo environment, and the delivery of drug moieties in a cell-specific manner. The multidisciplinary nature of this research led Dr. McCarthy to the Masonic Medical Research Institute in 2018 as an Associate Professor of Cardiovascular Medicine and the Scientific Operations Manager for the Institute, where his group aims to push the boundaries of nanomedicine, potentiating novel treatment options for an untold number of diseases.
Affiliations
- American Chemical Society
- American Heart Association
Professional Titles
- Associate Professor of Cardiovascular Medicine, Masonic Medical Research Institute
- Scientific Operations Manager, Masonic Medical Research Institute
Education
- 2003 Ph.D., Inorganic Chemistry University of Connecticut
- 1999 B.S., Chemistry Western New England College
Current Funding
National Institutes of Health
- R01HL122238 (PI: McCarthy)
- R01HL133153 (PI: McCarthy/Medoff)
- R01HL115141 (PI: Feinberg)
- R01HL102368 (PI: Kontaridis)
- R01HL122388 (PI: Jaffer)
Junior Faculty
Chase W. Kessinger, Ph.D.
Director, Imaging Core
Instructor of Cardiovascular Medicine
Research interests - Deep vein thrombosis and pulmonary embolism
Postdoctoral Fellows
- Khanh Ha, Ph.D - Novel imaging tools for platelet aggregation
- Rajendran Bose, Ph.D. - Targeted nanomaterials for the cell-specific drug delivery
- Muthunarayanan Muthiah, Ph.D - Targeted nanomaterials for the delivery of polynucleotides
Former fellows and students
Undergraduate Fellows
- Elijah Marris
- Alayna Trice
Selected Publications
, 2017. Atheroma Susceptible to Thrombosis Exhibit Impaired Endothelial Permeability In Vivo as Assessed by Nanoparticle-Based Fluorescence Molecular Imaging. Circ Cardiovasc Imaging 10.
, 2017. Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo. Eur Heart J 38(6):447-455
, 2017. Quantitative intravascular biological fluorescence-ultrasound imaging of coronary and peripheral arteries in vivo. Eur Heart J Cardiovasc Imaging 18(11):1253-1261
, 2015. Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study. Theranostics 5(12):1317-27
, 2015. Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis. Circ Res 117(6):502-512
, 2015. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring. PLoS One 10(2):e0116621
, 2015. In vivo nanoparticle assessment of pathological endothelium predicts the development of inflow stenosis in murine arteriovenous fistula. Arterioscler Thromb Vasc Biol 35(1):189-96
, 2014. RhoA signaling in cardiomyocytes protects against stress-induced heart failure but facilitates cardiac fibrosis. Sci Signal 7(348):ra100
, 2013. High-resolution optical mapping of inflammatory macrophages following endovascular arterial injury. Mol Imaging Biol 15(3):282-9
, 2012. Multifunctional nanoagent for thrombus-targeted fibrinolytic therapy. Nanomedicine (Lond) 7(7):1017-28
, 2012. Polymeric nanomaterials for islet targeting and immunotherapeutic delivery. Nano Lett 12(1):203-8
, 2012. Inflammation modulates murine venous thrombosis resolution in vivo: assessment by multimodal fluorescence molecular imaging. Arterioscler Thromb Vasc Biol 32(11):2616-24
, 2012. Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles. Methods Enzymol 508:191-209
, 2012. Molecular imaging of fibrin deposition in deep vein thrombosis using fibrin-targeted near-infrared fluorescence. JACC Cardiovasc Imaging 5(6):607-15
, 2012. meso-arylporpholactones and their reduction products. J Org Chem 77(15):6480-94
, 2011. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat Med 17(12):1680-4
, 2011. Helimeric porphyrinoids: stereostructure and chiral resolution of meso-tetraarylmorpholinochlorins. J Am Chem Soc 133(22):8740-52
, 2010. Multifunctional agents for concurrent imaging and therapy in cardiovascular disease. Adv Drug Deliv Rev 62(11):1023-30
, 2010. Nanomedicine and Cardiovascular Disease. Curr Cardiovasc Imaging Rep 3(1):42-49
, 2010. Targeted nanoagents for the detection of cancers. Mol Oncol 4(6):511-28
, 2010. Pioglitazone suppresses inflammation in vivo in murine carotid atherosclerosis: novel detection by dual-target fluorescence molecular imaging. Arterioscler Thromb Vasc Biol 30(10):1933-9
, 2010. A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small 6(18):2041-9
, 2009. Oxazine conjugated nanoparticle detects in vivo hypochlorous acid and peroxynitrite generation. J Am Chem Soc 131(43):15739-44
, 2009. High-yielding syntheses of hydrophilic conjugatable chlorins and bacteriochlorins. Org Biomol Chem 7(17):3430-6
, 2009. Synthesis and photophysical properties of sulfonamidophenyl porphyrins as models for activatable photosensitizers. J Org Chem 74(16):5894-901
, 2009. Multimodal nanoagents for the detection of intravascular thrombi. Bioconjug Chem 20(6):1251-5
, 2008. Multifunctional magnetic nanoparticles for targeted imaging and therapy. Adv Drug Deliv Rev 60(11):1241-51
, 2007. Targeted delivery of multifunctional magnetic nanoparticles. Nanomedicine (Lond) 2(2):153-67
, 2007. Novel peptide sequence ("IQ-tag") with high affinity for NIR fluorochromes allows protein and cell specific labeling for in vivo imaging. PLoS One 2(7):e665
, 2007. Model systems for fluorescence and singlet oxygen quenching by metalloporphyrins. ChemMedChem 2(3):360-5
, 2006. A macrophage-targeted theranostic nanoparticle for biomedical applications. Small 2(8-9):983-7
, 2006. Conjugation of a photosensitizer to an oligoarginine-based cell-penetrating peptide increases the efficacy of photodynamic therapy. ChemMedChem 1(4):458-63
, 2005. Polymeric nanoparticle preparation that eradicates tumors. Nano Lett 5(12):2552-6
, 2004. Synthesis of indaphyrins: meso-tetraarylsecochlorin-based porphyrinoids containing direct o-phenyl-to-beta-linkages. Org Biomol Chem 2(10):1484-91
, 2003. Free base meso-tetraaryl-morpholinochlorins and porpholactone from meso-tetraaryl-2,3-dihydroxy-chlorin. Org Lett 5(1):19-22
Publication list retrieved from NCBI using ImpactPubs
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