 Karen Taraszka Hastings, MD, PhD
Contact Information:
Education:
- Harvard Medical School, 2000
Research:
Antigen Processing and Immune Recognition of Melanoma
Melanoma is the most lethal form of skin cancer and is resistant to existing chemotherapeutic agents. Immunotherapy holds great promise in the treatment of metastatic melanoma because melanoma antigens have been identified and patients generate T and B cell responses specific for these antigens which in some cases lead to spontaneous remission. Effective immunotherapy requires presentation of tumor antigens in the context of MHC class II for the activation of CD4+ T lymphocytes to generate and sustain the anti-tumor immune response. My laboratory is interested in understanding the role of MHC class II-restricted antigen processing components, in particular gamma-interferon inducible lysosomal thiol reductase (GILT), in the development of an effective immune response against melanoma antigens.
Melanocyte differentiation antigens, including tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2 and pmel-17/gp100, are present in both benign melanocytes and melanoma cells. They are melanosomal integral membrane proteins involved in pigment (melanin) biosynthesis. These proteins contain a dileucine-based sorting signal which serves to target these antigens to the endocytic pathway leading to presentation by MHC class II. Recently, we determined that GILT is essential for the class II-restricted processing of a TRP-1 epitope in vitro. Furthermore, in a mouse model of auto-immune destruction of melanocytes (vitiligo), the absence of GILT delays the onset of disease. Our research is focused on the following areas:
1. Role of GILT in the activation of melanoma-specific CD4+ T lymphocytes
2. Role of GILT in the generation of protective immunity to melanoma
3. Expression of antigen processing components in human melanoma
These studies will identify key features of antigen processing required to generate an immune response to melanoma and may aid in the understanding of mechanisms that lead to immune evasion. The long-term goal of these studies is to aid the development of effective immunotherapy for melanoma.
Publications:
- Hastings KT, Irvine, KR, Antony, PA, Restifo, NP, Cresswell, P. (2007) GILT is essential for MHC class II processing of melanocyte differentiation antigen TRP-1. Annual Meeting of the Society for Investigative Dermatology, Los Angeles, CA (invited presentation).
- Girardi M, Hastings KT. Update on Cutaneous T-Cell Lymphoma: Pathogenesis and Therapy. DermQuest Thought Leader Commentary: Research Update (www.dermquest.com)
- Taraszka K, Glusac EJ, Wilson L, Girardi M. Mycosis Fungoides and Sézary Syndrome: Pathophysiology and Pathology in Lymphoid Neoplasms. Ed. Magrath, I. Hodder Arnold, London (in press).
- Hastings KT, Lackman, RL, Cresswell, P. Functional Requirements for the Lysosomal Thiol Reductase GILT in MHC Class II-Restricted Antigen Processing. Journal of Immunology, 177: 8569-8577, 2006.
- Taraszka K, Girardi M. Treatment of Cutaneous T Cell Lymphoma: Advances in Understanding Disease Behavior and Implications for Management. Year Book of Dermatology and Dermatologic Surgery. Eds. Theirs BH, Lang PG. Mosby, St. Louis. 1-26, 2003.
- Taraszka KS, Higgins JMG, Tan K, Mandelbrot DA, Wang JH, Brenner MB. Molecular Basis of Integrin αEß7 Recognition of E-cadherin. Journal of Experimental Medicine. 191 (9):1555-1567, 2000.
Peer-reviewed publications
Click here to see a listing of Peer-reviewed publications
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