Michael Hamblin
EDUCATIONAL TITLES
Associate Professor, Dermatology, Harvard Medical School
Associate Chemist, Dermatology, Massachusetts General Hospital
DF/HCC PROGRAM AFFILIATION
Gynecologic Cancers, Member
Research Abstract
Photodynamic therapy is a relatively new and exciting approach for treating cancers and other diseases. Many new photosensitizers have been developed in recent years, but it is still not clear what is the basic mechanism of the tumor localizing effect, and hence the optimum structure and formulation of the photosensitizer for any particular application is uncertain.
My particular area of interest is in the preparation and investigation of macromolecular conjugates of photosensitizers. Large molecules have very different biodistribution and pharmacokinetics compared to the small molecules which are generally used as photosensitizers. In addition it may be possible to use conjugates of photosensitizers with specifically targeted macromolecules to cancer cells and other defined cells and organs. I am also interested in the use of PDT to generate long-term specific anti-tumor immunity in immunocompetent mouse tumor models, and its relation to specific PDT parameters.
Examples of the above approaches are,
(a) the use of monoclonal antibody photosensitizer conjugates directed towards tumor associated antigens to target metastatic ovarian and colorectal cancer.
(b) the use of conjugates with polyamino acids which can vary in size, charge and hydrophobicity and can therefore produce different pharmacokinetics, biodistributions and enhanced phototoxicities.
(c) targeting pathogenic bacteria which may produce wound infections or other diseases with polycationic photosensitizer conjugates
(d) the use of conjugates with serum proteins such as albumin and lipoproteins which could have improved tumor targeting properties and specificity for macrophage type cells.
(e) the use of macromolecular conjugates to direct photosensitizers to subcellular locations such as lysosomes, mitochondria and membranes, where they could either increase the cytotoxic effect, or conversely not kill the cell but induce it to express cytokines or growth factors which could be advantageous in such areas as wound healing.
Publications
Barolet D, Christiaens F, Hamblin MR. Infrared and skin: Friend or foe. J. Photochem. Photobiol. B, Biol. 2016; 155:78-85. PubMed
Broekgaarden M, Weijer R, van Gulik TM, Hamblin MR, Heger M. Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies. Cancer Metastasis Rev 2015; 34:643-90. PubMed
Anzengruber F, Avci P, de Freitas LF, Hamblin MR. T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it? Photochem Photobiol Sci 2015. PubMed
Santos Z, Avci P, Hamblin MR. Drug discovery for alopecia: gone today, hair tomorrow. Expert Opin Drug Discov 2015; 10:269-92. PubMed
Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, Breckpot K, Brough D, Chaurio R, Cirone M, Coosemans A, Coulie PG, De Ruysscher D, Dini L, de Witte P, Dudek-Peric AM, Faggioni A, Fucikova J, Gaipl US, Golab J, Gougeon ML, Hamblin MR, Hemminki A, Herrmann M, Hodge JW, Kepp O, Kroemer G, Krysko DV, Land WG, Madeo F, Manfredi AA, Mattarollo SR, Maueroder C, Merendino N, Multhoff G, Pabst T, Ricci JE, Riganti C, Romano E, Rufo N, Smyth MJ, Sonnemann J, Spisek R, Stagg J, Vacchelli E, Vandenabeele P, Vandenberk L, Van den Eynde BJ, Van Gool S, Velotti F, Zitvogel L, Agostinis P. Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death. 2015; 6:588. PubMed
Xia Y, Gupta GK, Castano AP, Mroz P, Avci P, Hamblin MR. CpG oligodeoxynucleotide as immune adjuvant enhances photodynamic therapy response in murine metastatic breast cancer. J Biophotonics 2014. PubMed
Arany PR, Cho A, Hunt TD, Sidhu G, Shin K, Hahm E, Huang GX, Weaver J, Chen AC, Padwa BL, Hamblin MR, Barcellos-Hoff MH, Kulkarni AB, J Mooney D. Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration. Sci Transl Med 2014; 6:238ra69. PubMed
Wachowska M, Gabrysiak M, Muchowicz A, Bednarek W, Barankiewicz J, Rygiel T, Boon L, Mroz P, Hamblin MR, Golab J. 5-Aza-2'-deoxycytidine potentiates antitumour immune response induced by photodynamic therapy. Eur J Cancer 2014; 50:1370-81. PubMed
Vecchio D, Bhayana B, Huang L, Carrasco E, Evans CL, Hamblin MR. Structure-function relationships of Nile blue (EtNBS) derivatives as antimicrobial photosensitizers. Eur J Med Chem 2014; 75:479-91. PubMed
Gupta A, Dai T, Hamblin MR. Effect of red and near-infrared wavelengths on low-level laser (light) therapy-induced healing of partial-thickness dermal abrasion in mice. Lasers Med Sci 2014. PubMed
Mroz P, Vatansever F, Muchowicz A, Hamblin MR. Photodynamic therapy of murine mastocytoma induces specific immune responses against the cancer/testis antigen P1A. Cancer Res 2013; 73:6462-70. PubMed
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