McCarthy Lab

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

Junior Faculty

Chase W. Kessinger, Ph.D.

Instructor of Cardiovascular Medicine Director, Imaging Core Research interests - Deep vein thrombosis and pulmonary embolism

Postdoctoral Fellows 

  • Khanh Ha, Ph.D - Novel imaging tools for platelet aggregation
  • MD Nurunnabi, 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

Current Funding

National Institutes of Health

  • R01HL122238 (PI: McCarthy)
  • R01HL133153 (PI: McCarthy/Medoff)
  • R01HL115141 (PI: Feinberg)
  • R01HL102368 (PI: Kontaridis)
  • R01HL122388 (PI: Jaffer)

Selected Publications

Stein-Merlob AF; Hara T; McCarthy JR; Mauskapf A; Hamilton JA; Ntziachristos V; Libby P; Jaffer FA, 2017. Atheroma Susceptible to Thrombosis Exhibit Impaired Endothelial Permeability In Vivo as Assessed by Nanoparticle-Based Fluorescence Molecular Imaging.  Circ Cardiovasc Imaging 10.

Hara T; Ughi GJ; McCarthy JR; Erdem SS; Mauskapf A; Lyon SC; Fard AM; Edelman ER; Tearney GJ; Jaffer FA, 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

Bozhko D; Osborn EA; Rosenthal A; Verjans JW; Hara T; Kellnberger S; Wissmeyer G; Ovsepian SV; McCarthy JR; Mauskapf A; Stein AF; Jaffer FA; Ntziachristos V, 2017. Quantitative intravascular biological fluorescence-ultrasound imaging of coronary and peripheral arteries in vivo.  Eur Heart J Cardiovasc Imaging 18(11):1253-1261

Stein-Merlob AF; Kessinger CW; Erdem SS; Zelada H; Hilderbrand SA; Lin CP; Tearney GJ; Jaff MR; Reed GL; Henke PK; McCarthy JR; Jaffer FA, 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

Konishi M; Erdem SS; Weissleder R; Lichtman AH; McCarthy JR; Libby P, 2015. Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis.  Circ Res 117(6):502-512

Kessinger CW; Kim JW; Henke PK; Thompson B; McCarthy JR; Hara T; Sillesen M; Margey RJ; Libby P; Weissleder R; Lin CP; Jaffer FA, 2015. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.  PLoS One 10(2):e0116621

Cui J; Kessinger CW; McCarthy JR; Sosnovik DE; Libby P; Thadhani RI; Jaffer FA, 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

Lauriol J; Keith K; Jaffré F; Couvillon A; Saci A; Goonasekera SA; McCarthy JR; Kessinger CW; Wang J; Ke Q; Kang PM; Molkentin JD; Carpenter C; Kontaridis MI, 2014. RhoA signaling in cardiomyocytes protects against stress-induced heart failure but facilitates cardiac fibrosis.  Sci Signal 7(348):ra100

Saxena A; Kessinger CW; Thompson B; McCarthy JR; Iwamoto Y; Lin CP; Jaffer FA, 2013. High-resolution optical mapping of inflammatory macrophages following endovascular arterial injury.  Mol Imaging Biol 15(3):282-9

McCarthy JR; Sazonova IY; Erdem SS; Hara T; Thompson BD; Patel P; Botnaru I; Lin CP; Reed GL; Weissleder R; Jaffer FA, 2012. Multifunctional nanoagent for thrombus-targeted fibrinolytic therapy.  Nanomedicine (Lond) 7(7):1017-28

Ghosh K; Kanapathipillai M; Korin N; McCarthy JR; Ingber DE, 2012. Polymeric nanomaterials for islet targeting and immunotherapeutic delivery.  Nano Lett 12(1):203-8

Ripplinger CM; Kessinger CW; Li C; Kim JW; McCarthy JR; Weissleder R; Henke PK; Lin CP; Jaffer FA, 2012. Inflammation modulates murine venous thrombosis resolution in vivo: assessment by multimodal fluorescence molecular imaging.  Arterioscler Thromb Vasc Biol 32(11):2616-24

Erdem SS; Sazonova IY; Hara T; Jaffer FA; McCarthy JR, 2012. Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles.  Methods Enzymol 508:191-209

Hara T; Bhayana B; Thompson B; Kessinger CW; Khatri A; McCarthy JR; Weissleder R; Lin CP; Tearney GJ; Jaffer FA, 2012. Molecular imaging of fibrin deposition in deep vein thrombosis using fibrin-targeted near-infrared fluorescence.  JACC Cardiovasc Imaging 5(6):607-15

Brückner C; Ogikubo J; McCarthy JR; Akhigbe J; Hyland MA; Daddario P; Worlinsky JL; Zeller M; Engle JT; Ziegler CJ; Ranaghan MJ; Sandberg MN; Birge RR, 2012. meso-arylporpholactones and their reduction products.  J Org Chem 77(15):6480-94

Yoo H; Kim JW; Shishkov M; Namati E; Morse T; Shubochkin R; McCarthy JR; Ntziachristos V; Bouma BE; Jaffer FA; Tearney GJ, 2011. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo.  Nat Med 17(12):1680-4

Brückner C; Götz DC; Fox SP; Ryppa C; McCarthy JR; Bruhn T; Akhigbe J; Banerjee S; Daddario P; Daniell HW; Zeller M; Boyle RW; Bringmann G, 2011. Helimeric porphyrinoids: stereostructure and chiral resolution of meso-tetraarylmorpholinochlorins.  J Am Chem Soc 133(22):8740-52

McCarthy JR, 2010. Multifunctional agents for concurrent imaging and therapy in cardiovascular disease.  Adv Drug Deliv Rev 62(11):1023-30

McCarthy JR, 2010. Nanomedicine and Cardiovascular Disease.  Curr Cardiovasc Imaging Rep 3(1):42-49

McCarthy JR; Bhaumik J; Karver MR; Sibel Erdem S; Weissleder R, 2010. Targeted nanoagents for the detection of cancers.  Mol Oncol 4(6):511-28

Chang K; Francis SA; Aikawa E; Figueiredo JL; Kohler RH; McCarthy JR; Weissleder R; Plutzky J; Jaffer FA, 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

McCarthy JR; Korngold E; Weissleder R; Jaffer FA, 2010. A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis.  Small 6(18):2041-9

Panizzi P; Nahrendorf M; Wildgruber M; Waterman P; Figueiredo JL; Aikawa E; McCarthy J; Weissleder R; Hilderbrand SA, 2009. Oxazine conjugated nanoparticle detects in vivo hypochlorous acid and peroxynitrite generation.  J Am Chem Soc 131(43):15739-44

McCarthy JR; Bhaumik J; Merbouh N; Weissleder R, 2009. High-yielding syntheses of hydrophilic conjugatable chlorins and bacteriochlorins.  Org Biomol Chem 7(17):3430-6

Bhaumik J; Weissleder R; McCarthy JR, 2009. Synthesis and photophysical properties of sulfonamidophenyl porphyrins as models for activatable photosensitizers.  J Org Chem 74(16):5894-901

McCarthy JR; Patel P; Botnaru I; Haghayeghi P; Weissleder R; Jaffer FA, 2009. Multimodal nanoagents for the detection of intravascular thrombi.  Bioconjug Chem 20(6):1251-5

McCarthy JR; Weissleder R, 2008. Multifunctional magnetic nanoparticles for targeted imaging and therapy.  Adv Drug Deliv Rev 60(11):1241-51

McCarthy JR; Kelly KA; Sun EY; Weissleder R, 2007. Targeted delivery of multifunctional magnetic nanoparticles.  Nanomedicine (Lond) 2(2):153-67

Kelly KA; Carson J; McCarthy JR; Weissleder R, 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

McCarthy JR; Weissleder R, 2007. Model systems for fluorescence and singlet oxygen quenching by metalloporphyrins.  ChemMedChem 2(3):360-5

McCarthy JR; Jaffer FA; Weissleder R, 2006. A macrophage-targeted theranostic nanoparticle for biomedical applications.  Small 2(8-9):983-7

Choi Y; McCarthy JR; Weissleder R; Tung CH, 2006. Conjugation of a photosensitizer to an oligoarginine-based cell-penetrating peptide increases the efficacy of photodynamic therapy.  ChemMedChem 1(4):458-63

McCarthy JR; Perez JM; Brückner C; Weissleder R, 2005. Polymeric nanoparticle preparation that eradicates tumors.  Nano Lett 5(12):2552-6

McCarthy JR; Hyland MA; Brückner C, 2004. Synthesis of indaphyrins: meso-tetraarylsecochlorin-based porphyrinoids containing direct o-phenyl-to-beta-linkages.  Org Biomol Chem 2(10):1484-91

McCarthy JR; Jenkins HA; Brückner C, 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

.