Tayyaba Hasan is a Professor of Dermatology at the Wellman Center for Photomedicine, Harvard Medical School (HMS) and a Professor of Health Sciences and Technology (Harvard-MIT). She was the founding Director of the Office for Research Career Development at Massachusetts General Hospital until 2011. Dr. Hasan’s scientific efforts are focused on photochemistry-based approaches (photodynamic therapy, or PDT) for treatment and diagnosis of disease.  PDT is a photochemistry-based approach that is increasingly used to treat a wide number of diseases and requires: (i) light of appropriate wavelength, (ii) a light activatable chemical compound (photosensitizer or PS), and (iii) molecular oxygen.  PDT achieves its cytotoxic effect by producing active molecular species including oxygen radicals and singlet oxygen. The major aspects of PDT that are currently studied in our laboratory are:

• • Targeted PDT of tumors: Specificity in PDT emanates from: (i) preferential localization of the photosensitizer in tissues of interest, and (ii) spatial localization of the activating light. Nano-construct formulations of PS are being used to increase accumulation within the tumor.  The site directed localization, combined with selective irradiation, results in a dual selectivity that minimizes normal tissue damage.  Additional selectivity is achieved using targeting moieties such as antibodies and peptides.
  • Site-directed PDT of Microorganisms: (i) Infectious Diseases: The emergence of clinical isolates that are resistant to standard antimicrobial chemotherapeutics provides the necessary impetus to develop treatments that are not hindered by microbial resistant mutants.  PDT has a potential to be that treatment due to its acute nature of photokilling. We are developing microbial-specific photosensitizers for use in PDT that exploits the β-lactamase-producing phenotype of drug resistant pathogens. (ii) Rapid Fluorescence based assay for Antibiotic Efficacy: A β-lactamase sensitive PS has been constructed to result in a probe that, when cleaved (<30 min) produces a strong fluorescence signal. (iii) Cutaneous Leishmaniasis: Our interest is in the development of selective phototherapeutic agents for improved outcome.
  • Mechanism-based PDT combination therapies: We are interested in the biological consequences of PDT at both the cellular and molecular level. Our lab is developing mechanism-based PDT combination treatments in which one treatment will nullify the tumor survival responses resulting from the other treatment.  The strategies involve nano carriers with multiple inhibitors of oncogenic pathways.
  • Image-guided therapeutics: Understanding targeting and treatment effects is a key bottleneck in the development of new drugs and PDT treatment protocols. These projects include: (i) in vivo longitudinal quantification of disease progression and drug targeting via confocal microendoscopy, (ii) drug uptake information of individual organs and tissues using in vivo fluorescence imaging of whole small animals, (iii) non-invasive monitoring of in vivo tumor volume, vasculature, and oxygenation using ultrasound/photoacoustic imaging, and (iv) on-line, non-invasive fluorescent monitoring of cytotoxic singlet oxygen generation during PDT for personalizing PDT dose parameters in the clinic.
  • Model Development: Biological inadequacies in the 2D cultures and slow speed in animal models is a major barrier for evaluation of a broad array of combination treatments. Our laboratory is developing heterocellular 3D models with quantitative imaging as a viable, rapid platform for testing a larger variety of combination strategies, combined with biomarker monitoring by high throughput imaging and acoustic cell printing.  This work provides a platform for evaluating therapies for a broad array of cancers.

 

In cancer, the focus malignancies are ovarian, prostate, pancreas and head and neck cancers. In infections and infectious diseases, efforts are targeted toward developing microbial-enzyme-specific photoactivatable molecules for use in PDT. Target organisms in the infectious diseases are leishmaniasis, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus. In addition, optimal imaging strategies develop target specific molecular probes for in situ monitoring of cellular processes during treatment such as the up-regulation of vascular endothelial growth factor.