Laboratory of Immunogenetics

Herbert C. Morse, M.D.

Chief, Virology and Cellular Immunology Section, LIG

Description of Research Program

Studies in the Virology and Cellular Immunology Section are focused on understanding mechanisms involved in normal B-cell differentiation and function and in the development of B-cell lymphomas. Other work centers on understanding host and viral determinants of murine leukemia virus (MuLV) expression and their effects on the immune system. Basic biologic problems are probed through the use of congenic, transgenic, and knockout mice; analyses of lymphoma cell lines; DNA and tissue microarrays; and molecular and cell biology.

Studies in LIP were the first to define mouse marginal zone lymphoma (MZL) as the murine counterpart of the human disorder.  LIP scientists and collaborators showed that p53-knockout mice developed MZL at high frequency and much earlier than wild type mice. Mutations of caretake genes in MZL are suspected but yet to be defined.

Work from the Virology and Cellular Immunology Section provided the foundation for developing new consensus nomenclatures for mouse hematopoietic neoplasms based primarily on histopathologic criteria. This classification system is being strengthened and revised through the use of gene expression profiling, immunohistochemical analyses of tissue arrays and examination of genes affected by MuLV proviral insertional mutagenesis.

A variety of bioinformatic approaches to examining data from DNA microarrays are used to identify genes involved in processes of B-cell differentiation and transformation. All this work is facilitated by the availability of a large, unparalleled repository of tissue samples, DNA, and material for frozen sections from primary lymphomas; and a large number of derivative cell lines. Important directions can be extended to human B cells and lymphomas through productive collaborations.

Selected Recent Publications

(View list in PubMed.)

Hao X, Fredrickson TN, Chattopadhyay SK, Han W, Qi CF, Wang Z, Ward JM, Hartley JW, Morse HC 3rd. The histopathologic and molecular basis for the diagnosis of histiocytic sarcoma and histiocyte-associated lymphoma of mice. Vet Pathol. 2010 May;47(3):434-45.

Qi CF, Shin DM, Li Z, Wang H, Feng J, Hartley JW, Fredrickson TN, Kovalchuk AL, Morse HC 3rd. Anaplastic plasmacytomas: relationships to normal memory B cells and plasma cell neoplasms of immunodeficient and autoimmune mice. J Pathol. 2010 May;221(1):106-16.

Li Z, Wang H, Xue L, Shin DM, Roopenian D, Xu W, Qi CF, Sangster MY, Orihuela CJ, Tuomanen E, Rehg JE, Cui X, Zhang Q, Morse HC 3rd, Morris SW. Eµ-BCL10 mice exhibit constitutive activation of both canonical and noncanonical NF-κB pathways generating marginal zone (MZ) B-cell expansion as a precursor to splenic MZ lymphoma. Blood. 2009 Nov 5;114(10):4158-68.

Zhou JX, Lee CH, Qi CF, Wang H, Naghashfar Z, Abbasi S, Morse HC 3rd. IFN regulatory factor 8 regulates MDM2 in germinal center B cells. J Immunol. 2209 Sep 1;183(5):3188-94.

Shin DM, Shaffer DJ, Wang H, Roopenian DC, Morse HC 3rd. NOTCH is part of the transcriptional network regulating cell growth and survival in mouse plasmacytomas. Cancer Res. 2008 Nov 15;68:9202-11.

Wang H, Lee CH, Qi C, Tailor P, Feng J, Abbasi S, Atsumi T, Morse HC 3rd. IRF8 regulates B-cell lineage specification, commitment, and differentiation. Blood. 2008 Nov 15;112(10):4028-38.

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