Thomas Jefferson University - Larry A Harshyne Jr
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Larry A Harshyne Jr
Neurosurgery
Thomas Jefferson University
Department of Neurosurgery
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Mailing Address
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JHN, suite 410
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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My research interests include various interactions between gliomas and the immune system. We are currently developing a dendritic cell-based vaccine for therapy of gliomas. Dendritic cells play an instrumental role in initiating and orchestrating immune responses within the body. Dendritic cells are located through out the body where they sample the local environment for traces of pathogens or tumors. Pieces of tumors are engulfed by dendritic cells that then migrate to draining lymph nodes. Here, dendritic cells activate lymphocytes. Activated lymphocytes then enter the circulation and attack infected or malignant cells. Tumors, on the other hand, have evolved many ways to evade detection by the immune system and to actively suppress anti-tumor immune responses. Our vaccine attempts to circumvent these evasive tricks utilized by gliomas by feeding dendritic cells pieces of dead and dying tumor cells in a culture dish. These loaded-dendritic cells are then injected back into patients to assume their natural role. Dendritic cell vaccination provides a boost for the immune system in hopes of preventing tumors recurrence.
Our other area of interest focuses on gliomas themselves, and particularly, how they evade the immune system. Gliomas possess multiple mechanisms to shut off or evade the immune system. We have found that glioma patients have an increased level of regulatory T cells. Regulatory T cells primary function is to keep the immune system at bay; that is to say, they work to prevent autoimmunity. To accomplish this they employ numerous receptors, including CTLA-4, and secreted molecules such as TGF-beta and IL-10. We are currently developing ways to counteract these anti-immune devices and towards elucidating the mechanism(s) responsible for increasing these cells in gliomas patients. In addition, we have also established that gliomas express numerous inhibitory receptors on their cell surface. These receptors (B7-H1, -DC, -H3) belong to the B7 super-family and are capable of de-activating T cells. We believe in order for an anti-glioma vaccine to be successful, it must be multifaceted and not only boost immunity, but also counteract immunosuppression induced by the tumor.
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Other Expertise
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Cellular Immunology
Fluorescent detection; various forms of microscopy and flow cytometry
Computers; hardware, software, and networking
Basic Molecular Biology; PCR, RT-PCR, Western blotting
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Keywords
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immunology; cancer; gliomas; immunotherapy; dendritic cells; regulatory T cells
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Publications
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- Cui J, Han SY, Wang C, Su W, Harshyne L, Holgado-Madruga M, Wong AJ. c-Jun NH2-Terminal Kinase 2{alpha}2 Promotes the Tumorigenicity of Human Glioblastoma Cells. Cancer Research 2006 Oct 15;66(20):10024-31.
- Tang, J., Flomenberg, P., Harshyne, L., Kenyon, L., and Andrews, D.W. Glioblastoma patients exhibit circulating tumor-specific CD8+ T cells. Clinical Cancer Research. 2005, 11(14): 5292-9. PMID: 16033848
- Pallozzi WA, Harshyne LA, Wilkoski LM, Semler GP, Conboy TA, Jendrowski SM, Klein HJ. Novel training concepts and techniques used to increase safety awareness in the laboratory animal facility. Lab Anim (NY). 2003 Jun;32(6):38-42. PMID: 12817278
- Harshyne LA, Zimmer MI, Watkins SC, Barratt-Boyes SM. A role for class A scavenger receptor in dendritic cell nibbling from live cells. J Immunol. 2003 Mar 1;170(5):2302-9. PMID: 12594251
- Barratt-Boyes SM, Zimmer MI, Harshyne L. Changes in dendritic cell migration and activation during SIV infection suggest a role in initial viral spread and eventual immunosuppression. J Med Primatol. 2002 Aug;31(4-5):186-93. PMID: 12390541
- Harshyne LA, Watkins SC, Gambotto A, Barratt-Boyes SM. Dendritic cells acquire antigens from live cells for cross-presentation to CTL. J Immunol. 2001 Mar 15;166(6):3717-23. Erratum in: J Immunol 2001 May 1;166(9):5840. PMID: 11238612
- Barratt-Boyes SM, Zimmer MI, Harshyne LA, Meyer EM, Watkins SC, Capuano S 3rd, Murphey-Corb M, Falo LD Jr, Donnenberg AD. Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J Immunol. 2000 Mar 1;164(5):2487-95. PMID: 10679086
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Individual Expertise profile of
Larry A Harshyne Jr, Copyright © Larry A Harshyne Jr.
Last Updated
by Larry Harshyne Jr : Tuesday, July 29, 2008 2:47:15 PM
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