Tayyaba Hasan, Ph.D.

Professor of Dermatology, Harvard Medical School

Phone: 617-726-6856

Fax: 617-726-8566

E-mail: thasan@partners.org

Complete curriculum vitae is available in text format.

photo of Tayyaba Hasan, Ph.D.

Positions held

  • 1980. Ph.D., University of Arkansas, Fayettville, AR
  • 1980-1982. Postdoctoral Fellow, Department of Chemistry, University of Pennsylvania
  • 1982-1987. Research Associate, Department of Dermatology, Harvard Medical School
  • 1982-1989. Assistant Biochemist, Department of Dermatology, Massachusetts General Hospital
  • 1987-1991. Assistant Professor of Dermatology (Biochemistry), Harvard Medical School
  • 1989-1994. Associate Biochemist, Department of Dermatology, Massachusetts General Hospital
  • 1990. Visiting Professor, University Clinic Ulm, Ulm Germany
  • 1990-1991, Assistant Professor of Dermatology, Health Science Technology, Massachusetts Institute of Technology
  • 1991-2000, Associate Professor of Dermatology (Biochemistry), Harvard Medical School
  • 1991-2000, Associate Professor of Dermatology, Health Science Technology, Massachusetts Institute of Technology
  • 1994-. Biochemist, Department of Dermatology, Massachusetts General Hospital
  • 2000-. Professor of Dermatology, Wellman Laboratories of Photomedicine, Department of Dermatology, Harvard Medical School

Role and rationale in PPG

Director of Program Project, Director of Core A, Leader of Project 4

The goal of this Program is an integrated approach to the optimization of photodynamic therapy (PDT). The Program has a translational approach and encompasses elements of PDT from basic research in cellular mechanisms through treatment of appropriate animal models of cancer and sophisticated apparatus for feedback dosimetry, to a clinical trial for Barrett's esophagus: it is truly a "bench-to-bedside" proposal. We will concentrate on three broad areas of research: modulation of the target tissue with the aim of increasing the tumor sensitivity and selectivity of the treatment, determination of methods of optimizing local control of tumors without increasing the risk of distant metastasis, and dosimetric tools with the potential for real-time on-line measurement of critical parameters. There are clinical components comprising trials to treat Barrett's esophagus and psoriasis with a combination of differentiation therapy and PDT. Hence the Program will encompass the translation of basic science to human therapeutic studies and contains an integrated approach to PDT covering broad areas of research starting from the basic science involved in studying cellular differentiation and transcription factors to the selection of appropriate animal models for studying metastasis, to technological advances in modern dosimetric tools, and ending with a clinical trial that aims to help patients suffering from a distressing and potentially life-threatening disease.

Project 4 addresses the relationship between PDT and distant metastasis, a consequence that may not surface for years after the primary treatment. The motivations for such a study are: (a) A number of interventional treatments of prostate cancer (PCa), which involve physical manipulations similar to those involved in PDT, are believed to encourage metastatic colonization, presumably by shedding of tumor cells. PDT may logically be considered an attractive option for the treatment of advanced localized prostate cancer and indeed has very recently received FDA approval for Phase I clinical trials. It is important to establish what, if any, the effects of PDT might be on metastasis. (b) Surprisingly little is known about this aspect of PDT. Our studies with BPD as the PS in an orthotopic rat PCa model and the orthotopic model observed an increase in distant metastasis following PDT. Recently, we were able to confirm these data in a human PCa implanted in SCID mice. There are many factors that determine metastatic colonization following interventional treatment including (but not limited to) the induction of hypoxia, loss or induction of cellular receptors, loss of intercellular and cell-extracellular matrix (ECM) adhesion, vascular damage caused by PDT and differentiation status of tumor. It is the aim of Project 4 to establish which aspects of PDT response, if any exacerbate or inhibit metastasis. Techniques and information gathered in Projects 1-3 such as the effect of differentiation, extent of hypoxia and optimal dosimetry, will be used for elucidating factors affecting PDT control of metastasis.

Major research interests

Photodynamic therapy (PDT) is a process in which a light-responsive chemical, when exposed to the appropriate wavelength of light, is activated to undergo either a photophysical process or to initiate photochemistry, producing molecular species which can interact with biological targets (photosensitization). Such interactions can be exploited for biomedical applications or for basic studies. The three major aspects of photoactivation that our laboratory is engaged in are:

  1. Site-directed photochemistry

    Photosensitization is exploited for the destruction of tumors and certain non-neoplastic target tissues in an approach termed photodynamic therapy (PDT). Compounds, typically porphyrins, are localized in target cells and tissues and upon light activation cause destruction at sites of localization. An advantage of this approach is that it minimizes normal tissue damage due to the dual selectivity inherent in the technique. (i) Preferential localization of the photosensitizer, (ii) spatial localization of the activating light. The more specific the localization of the photosensitizer, the more efficient and selective the response.

    Two of our goals in the PDT area are:

    1. Establishing methods for site-specific photosensitization. Techniques are being developed for localization of photosensitizers at specific cellular and subcellular target sites by molecular modification or by using macromolecules such as monoclonal antibodies, peptides and microspheres for delivery. The photochemical and physiological parameters that determine the efficacy and transport of these different chemical constructs in vivo are being investigated. As these macromolecular moieties can be made to differ in their size and charge, their interaction with different cell and tissue types (e.g. endothelial cells, tumor cells, extracellular matrix proteins) is expected to vary, thereby affecting photosensitivity and localization. Site-directed PDT is being studied in ovarian and prostate cancers for the specific inactivation of molecular targets such as the epidermal growth factor receptor (EGFR) in order to modulate cell proliferation. Peptide-based targeting of bacteria is being studied to control infectious diseases.
    2. Understanding the basis of photodynamic localization and destruction, for example the significance of neovascularization, vascular permeability and differentiation in selectivity and response to PDT. Specific molecular interactions between the photosensitizers and neo-endothelial cell surface molecules such as the low density lipoprotein (LDL) receptor are being studied. This concept of LDL-receptor targeting of neovascularization, initially investigated for ocular neovascularization, an application that is now in clinical trials. Other molecular factors and applications for neovascular targeting are being investigated.

  2. Synthetic and mechanistic studies

    In synthetic studies, photosensitization is being used as a tool for the preparation of biologically useful molecules e.g. using photoaffinity labeling to synthesize and characterize nucleotide binding sites on monoclonal antibodies where the nucleotide has been linked to peptides and photosensitizers.

    In mechanistic studies, the biological consequences of PDT at the animal, cellular and molecular levels are being investigated. For example, the photodynamic destruction of primary prostate cancer in an orthotopic rat tumor model shows good local control, but an increase in lung metastasis. Based on initial studies our current hypothesis is that there are two major factors responsible for this increase in metastatic spread. PDT-induced transient decrease in cellular adhesion to ECM via specific integrins and the high expression of vascular endothelium growth factor (VEGF) in the normal prostate tissue. (c) Another mechanistic project uses targeted photosensitization to clarify the role of growth factors and of subcutaneous fibroblasts in wound repair.

  3. Fluorescence diagnostics

    The ability to specifically localize molecules that can be photoactivated is being explored for optical imaging. For example, it has been demonstrated that certain cancers at an early stage of development over-express EGFR. EGFR ligands are linked to long-wavelength-absorbing molecules that can both fluoresce and photosensitize. This is being investigated for early detection and destruction of target cancers.

Recent publications

Coming soon. For now, please search PubMed.