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.

 

Jason McCarthy, Ph.D.
Associate Professor of Cardiovascular Medicine, MMRI
Scientific Operations Manager, MMRI

Email – , 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.
Histology/Imaging/Surgery Core Manager
Instructor of Cardiovascular Medicine 
Research interests - Deep vein thrombosis and pulmonary embolism

Senior Scientists

Rajendran Bose, Ph.D. - Senior Nanomaterials Scientist
Research interests - Targeted nanomaterials for the cell-specific drug delivery

Postdoctoral Fellows 

-Khanh Ha, Ph.D 
Research interests - Synthesis of novel imaging agents

Research Assistant

-Jeffrey Cheng

  1. Bose, RJ, Kumar, US, Garcia-Marques, F, Zeng, Y, Habte, F, McCarthy, JR et al.. Engineered Cell-Derived Vesicles Displaying Targeting Peptide and Functionalized with Nanocarriers for Therapeutic microRNA Delivery to Triple-Negative Breast Cancer in Mice. Adv Healthc Mater. 2022;11 (5):e2101387. doi: 10.1002/adhm.202101387. PubMed PMID:34879180 PubMed Central PMC8891081.
  2. Saito, M, Moore-Lotridge, SN, Uppuganti, S, Egawa, S, Yoshii, T, Robinette, JP et al.. Determining the pharmacologic window of bisphosphonates that mitigates severe injury-induced osteoporosis and muscle calcification, while preserving fracture repair. Osteoporos Int. 2022;33 (4):807-820. doi: 10.1007/s00198-021-06208-7. PubMed PMID:34719727 .
  3. Ha, K, Zheng, X, Kessinger, CW, Mauskapf, A, Li, W, Kawamura, Y et al.. In Vivo Platelet Detection Using a Glycoprotein IIb/IIIa-Targeted Near-Infrared Fluorescence Imaging Probe. ACS Sens. 2021;6 (6):2225-2232. doi: 10.1021/acssensors.1c00124. PubMed PMID:34056903 PubMed Central PMC8767556.
  4. Bose, RJ, Ha, K, McCarthy, JR. Bio-inspired nanomaterials as novel options for the treatment of cardiovascular disease. Drug Discov Today. 2021;26 (5):1200-1211. doi: 10.1016/j.drudis.2021.01.035. PubMed PMID:33561512 PubMed Central PMC8205945.
  5. Loo, YS, Bose, RJ, McCarthy, JR, Mat Azmi, ID, Madheswaran, T. Biomimetic bacterial and viral-based nanovesicles for drug delivery, theranostics, and vaccine applications. Drug Discov Today. 2021;26 (4):902-915. doi: 10.1016/j.drudis.2020.12.017. PubMed PMID:33383213 .
  6. Bose, RJC, Tharmalingam, N, Choi, Y, Madheswaran, T, Paulmurugan, R, McCarthy, JR et al.. Combating Intracellular Pathogens with Nanohybrid-Facilitated Antibiotic Delivery. Int J Nanomedicine. 2020;15 :8437-8449. doi: 10.2147/IJN.S271850. PubMed PMID:33162754 PubMed Central PMC7642590.
  7. Unudurthi, SD, Luthra, P, Bose, RJC, McCarthy, JR, Kontaridis, MI. Cardiac inflammation in COVID-19: Lessons from heart failure. Life Sci. 2020;260 :118482. doi: 10.1016/j.lfs.2020.118482. PubMed PMID:32971105 PubMed Central PMC7505073.
  8. Bose, RJC, McCarthy, JR. Direct SARS-CoV-2 infection of the heart potentiates the cardiovascular sequelae of COVID-19. Drug Discov Today. 2020;25 (9):1559-1560. doi: 10.1016/j.drudis.2020.06.021. PubMed PMID:32592868 PubMed Central PMC7313487.
  9. Jing, JLJ, Pei Yi, T, Bose, RJC, McCarthy, JR, Tharmalingam, N, Madheswaran, T et al.. Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations. Int J Environ Res Public Health. 2020;17 (9):. doi: 10.3390/ijerph17093326. PubMed PMID:32403261 PubMed Central PMC7246736.
  10. Bose, RJC, Tharmalingam, N, Garcia Marques, FJ, Sukumar, UK, Natarajan, A, Zeng, Y et al.. Reconstructed Apoptotic Bodies as Targeted "Nano Decoys" to Treat Intracellular Bacterial Infections within Macrophages and Cancer Cells. ACS Nano. 2020;14 (5):5818-5835. doi: 10.1021/acsnano.0c00921. PubMed PMID:32347709 PubMed Central PMC9116903.
  11. Cui, J, Kessinger, CW, Jhajj, HS, Grau, MS, Misra, S, Libby, P et al.. Atorvastatin Reduces In Vivo Fibrin Deposition and Macrophage Accumulation, and Improves Primary Patency Duration and Maturation of Murine Arteriovenous Fistula. J Am Soc Nephrol. 2020;31 (5):931-945. doi: 10.1681/ASN.2019060612. PubMed PMID:32152232 PubMed Central PMC7217409.
  12. Baker, CE, Moore-Lotridge, SN, Hysong, AA, Posey, SL, Robinette, JP, Blum, DM et al.. Bone Fracture Acute Phase Response-A Unifying Theory of Fracture Repair: Clinical and Scientific Implications. Clin Rev Bone Miner Metab. 2018;16 (4):142-158. doi: 10.1007/s12018-018-9256-x. PubMed PMID:30930699 PubMed Central PMC6404386.
  13. Stein-Merlob, AF, Hara, T, McCarthy, JR, Mauskapf, A, Hamilton, JA, Ntziachristos, V et al.. Atheroma Susceptible to Thrombosis Exhibit Impaired Endothelial Permeability In Vivo as Assessed by Nanoparticle-Based Fluorescence Molecular Imaging. Circ Cardiovasc Imaging. 2017;10 (5):. doi: 10.1161/CIRCIMAGING.116.005813. PubMed PMID:28487316 PubMed Central PMC5509162.
  14. Bozhko, D, Osborn, EA, Rosenthal, A, Verjans, JW, Hara, T, Kellnberger, S et al.. Quantitative intravascular biological fluorescence-ultrasound imaging of coronary and peripheral arteries in vivo. Eur Heart J Cardiovasc Imaging. 2017;18 (11):1253-1261. doi: 10.1093/ehjci/jew222. PubMed PMID:28031233 PubMed Central PMC5837649.
  15. Hara, T, Ughi, GJ, McCarthy, JR, Erdem, SS, Mauskapf, A, Lyon, SC et al.. Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo. Eur Heart J. 2017;38 (6):447-455. doi: 10.1093/eurheartj/ehv677. PubMed PMID:26685129 PubMed Central PMC5837565.
  16. Stein-Merlob, AF, Kessinger, CW, Erdem, SS, Zelada, H, Hilderbrand, SA, Lin, CP et al.. Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study. Theranostics. 2015;5 (12):1317-27. doi: 10.7150/thno.12494. PubMed PMID:26516370 PubMed Central PMC4615735.
  17. Konishi, M, Erdem, SS, Weissleder, R, Lichtman, AH, McCarthy, JR, Libby, P et al.. Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis. Circ Res. 2015;117 (6):502-512. doi: 10.1161/CIRCRESAHA.115.306364. PubMed PMID:26199323 PubMed Central PMC4553143.
  18. Kessinger, CW, Kim, JW, Henke, PK, Thompson, B, McCarthy, JR, Hara, T et al.. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring. PLoS One. 2015;10 (2):e0116621. doi: 10.1371/journal.pone.0116621. PubMed PMID:25680183 PubMed Central PMC4334538.
  19. Cui, J, Kessinger, CW, McCarthy, JR, Sosnovik, DE, Libby, P, Thadhani, RI et al.. In vivo nanoparticle assessment of pathological endothelium predicts the development of inflow stenosis in murine arteriovenous fistula. Arterioscler Thromb Vasc Biol. 2015;35 (1):189-96. doi: 10.1161/ATVBAHA.114.304483. PubMed PMID:25395614 PubMed Central PMC4270948.
  20. Lauriol, J, Keith, K, Jaffré, F, Couvillon, A, Saci, A, Goonasekera, SA et al.. RhoA signaling in cardiomyocytes protects against stress-induced heart failure but facilitates cardiac fibrosis. Sci Signal. 2014;7 (348):ra100. doi: 10.1126/scisignal.2005262. PubMed PMID:25336613 PubMed Central PMC4300109.
  21. Saxena, A, Kessinger, CW, Thompson, B, McCarthy, JR, Iwamoto, Y, Lin, CP et al.. High-resolution optical mapping of inflammatory macrophages following endovascular arterial injury. Mol Imaging Biol. 2013;15 (3):282-9. doi: 10.1007/s11307-012-0599-2. PubMed PMID:23090852 PubMed Central PMC3650124.
  22. Ripplinger, CM, Kessinger, CW, Li, C, Kim, JW, McCarthy, JR, Weissleder, R et al.. Inflammation modulates murine venous thrombosis resolution in vivo: assessment by multimodal fluorescence molecular imaging. Arterioscler Thromb Vasc Biol. 2012;32 (11):2616-24. doi: 10.1161/ATVBAHA.112.251983. PubMed PMID:22995524 PubMed Central PMC3516622.
  23. Brückner, C, Ogikubo, J, McCarthy, JR, Akhigbe, J, Hyland, MA, Daddario, P et al.. meso-arylporpholactones and their reduction products. J Org Chem. 2012;77 (15):6480-94. doi: 10.1021/jo300963m. PubMed PMID:22734444 PubMed Central PMC3411881.
  24. Hara, T, Bhayana, B, Thompson, B, Kessinger, CW, Khatri, A, McCarthy, JR et al.. Molecular imaging of fibrin deposition in deep vein thrombosis using fibrin-targeted near-infrared fluorescence. JACC Cardiovasc Imaging. 2012;5 (6):607-15. doi: 10.1016/j.jcmg.2012.01.017. PubMed PMID:22698530 PubMed Central PMC3376390.
  25. Erdem, SS, Sazonova, IY, Hara, T, Jaffer, FA, McCarthy, JR. Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles. Methods Enzymol. 2012;508 :191-209. doi: 10.1016/B978-0-12-391860-4.00010-0. PubMed PMID:22449927 .
  26. McCarthy, JR, Sazonova, IY, Erdem, SS, Hara, T, Thompson, BD, Patel, P et al.. Multifunctional nanoagent for thrombus-targeted fibrinolytic therapy. Nanomedicine (Lond). 2012;7 (7):1017-28. doi: 10.2217/nnm.11.179. PubMed PMID:22348271 PubMed Central PMC3360120.
  27. Ghosh, K, Kanapathipillai, M, Korin, N, McCarthy, JR, Ingber, DE. Polymeric nanomaterials for islet targeting and immunotherapeutic delivery. Nano Lett. 2012;12 (1):203-8. doi: 10.1021/nl203334c. PubMed PMID:22196766 PubMed Central PMC3280082.
  28. Yoo, H, Kim, JW, Shishkov, M, Namati, E, Morse, T, Shubochkin, R et al.. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat Med. 2011;17 (12):1680-4. doi: 10.1038/nm.2555. PubMed PMID:22057345 PubMed Central PMC3233646.
  29. Brückner, C, Götz, DC, Fox, SP, Ryppa, C, McCarthy, JR, Bruhn, T et al.. Helimeric porphyrinoids: stereostructure and chiral resolution of meso-tetraarylmorpholinochlorins. J Am Chem Soc. 2011;133 (22):8740-52. doi: 10.1021/ja202451t. PubMed PMID:21534626 .
  30. McCarthy, JR, Bhaumik, J, Karver, MR, Sibel Erdem, S, Weissleder, R. Targeted nanoagents for the detection of cancers. Mol Oncol. 2010;4 (6):511-28. doi: 10.1016/j.molonc.2010.08.003. PubMed PMID:20851695 PubMed Central PMC2981649.
  31. McCarthy, JR, Korngold, E, Weissleder, R, Jaffer, FA. A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small. 2010;6 (18):2041-9. doi: 10.1002/smll.201000596. PubMed PMID:20721949 PubMed Central PMC3018665.
  32. Chang, K, Francis, SA, Aikawa, E, Figueiredo, JL, Kohler, RH, McCarthy, JR et al.. Pioglitazone suppresses inflammation in vivo in murine carotid atherosclerosis: novel detection by dual-target fluorescence molecular imaging. Arterioscler Thromb Vasc Biol. 2010;30 (10):1933-9. doi: 10.1161/ATVBAHA.110.206342. PubMed PMID:20689078 PubMed Central PMC3030475.
  33. McCarthy, JR. Multifunctional agents for concurrent imaging and therapy in cardiovascular disease. Adv Drug Deliv Rev. 2010;62 (11):1023-30. doi: 10.1016/j.addr.2010.07.004. PubMed PMID:20654664 PubMed Central PMC2974776.
  34. McCarthy, JR. Nanomedicine and Cardiovascular Disease. Curr Cardiovasc Imaging Rep. 2010;3 (1):42-49. doi: 10.1007/s12410-009-9002-3. PubMed PMID:20369034 PubMed Central PMC2848940.
  35. Panizzi, P, Nahrendorf, M, Wildgruber, M, Waterman, P, Figueiredo, JL, Aikawa, E et al.. Oxazine conjugated nanoparticle detects in vivo hypochlorous acid and peroxynitrite generation. J Am Chem Soc. 2009;131 (43):15739-44. doi: 10.1021/ja903922u. PubMed PMID:19817443 PubMed Central PMC2773134.
  36. McCarthy, JR, Bhaumik, J, Merbouh, N, Weissleder, R. High-yielding syntheses of hydrophilic conjugatable chlorins and bacteriochlorins. Org Biomol Chem. 2009;7 (17):3430-6. doi: 10.1039/b908713c. PubMed PMID:19675897 PubMed Central PMC2749955.
  37. Bhaumik, J, Weissleder, R, McCarthy, JR. Synthesis and photophysical properties of sulfonamidophenyl porphyrins as models for activatable photosensitizers. J Org Chem. 2009;74 (16):5894-901. doi: 10.1021/jo900832y. PubMed PMID:19610602 PubMed Central PMC2888918.
  38. McCarthy, JR, Patel, P, Botnaru, I, Haghayeghi, P, Weissleder, R, Jaffer, FA et al.. Multimodal nanoagents for the detection of intravascular thrombi. Bioconjug Chem. 2009;20 (6):1251-5. doi: 10.1021/bc9001163. PubMed PMID:19456115 PubMed Central PMC2733224.
  39. McCarthy, JR, Weissleder, R. Multifunctional magnetic nanoparticles for targeted imaging and therapy. Adv Drug Deliv Rev. 2008;60 (11):1241-1251. doi: 10.1016/j.addr.2008.03.014. PubMed PMID:18508157 PubMed Central PMC2583936.
  40. McCarthy, JR, Kelly, KA, Sun, EY, Weissleder, R. Targeted delivery of multifunctional magnetic nanoparticles. Nanomedicine (Lond). 2007;2 (2):153-67. doi: 10.2217/17435889.2.2.153. PubMed PMID:17716118 .
  41. Kelly, KA, Carson, J, McCarthy, JR, Weissleder, R. Novel peptide sequence ("IQ-tag") with high affinity for NIR fluorochromes allows protein and cell specific labeling for in vivo imaging. PLoS One. 2007;2 (7):e665. doi: 10.1371/journal.pone.0000665. PubMed PMID:17653285 PubMed Central PMC1919420.
  42. McCarthy, JR, Weissleder, R. Model systems for fluorescence and singlet oxygen quenching by metalloporphyrins. ChemMedChem. 2007;2 (3):360-5. doi: 10.1002/cmdc.200600244. PubMed PMID:17245681 .
  43. McCarthy, JR, Jaffer, FA, Weissleder, R. A macrophage-targeted theranostic nanoparticle for biomedical applications. Small. 2006;2 (8-9):983-7. doi: 10.1002/smll.200600139. PubMed PMID:17193154 .
  44. Choi, Y, McCarthy, JR, Weissleder, R, Tung, CH. Conjugation of a photosensitizer to an oligoarginine-based cell-penetrating peptide increases the efficacy of photodynamic therapy. ChemMedChem. 2006;1 (4):458-63. doi: 10.1002/cmdc.200500036. PubMed PMID:16892381 .
  45. McCarthy, JR, Perez, JM, Brückner, C, Weissleder, R. Polymeric nanoparticle preparation that eradicates tumors. Nano Lett. 2005;5 (12):2552-6. doi: 10.1021/nl0519229. PubMed PMID:16351214 .
  46. McCarthy, JR, Hyland, MA, Brückner, C. Synthesis of indaphyrins: meso-tetraarylsecochlorin-based porphyrinoids containing direct o-phenyl-to-beta-linkages. Org Biomol Chem. 2004;2 (10):1484-91. doi: 10.1039/b401629g. PubMed PMID:15136804 .
  47. McCarthy, JR, Jenkins, HA, Brückner, C. Free base meso-tetraaryl-morpholinochlorins and porpholactone from meso-tetraaryl-2,3-dihydroxy-chlorin. Org Lett. 2003;5 (1):19-22. doi: 10.1021/ol027072a. PubMed PMID:12509880 .
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