Research Program:
Our lab is focused on three different research aspects.

Control of Activation and Signaling in Cells of the Immune System - For this project, we seek to define how cells of the immune system know when and how to be activated. The immune system includes the white blood cells that fight off infections, cancer, and other diseases, but when things go wrong, they are also responsible for autoimmune conditions including juvenile diabetes and rheumatoid arthritis, allergies and asthma.

The Genetic Basis of Cancer - For this project, we are interested in understanding the genetic basis of cancer. For this project, we study naturally occurring cancers of dogs, which closely resemble those seen in people, as well as cultured cells and laboratory animal models that allow us to ask research questions under highly controlled conditions. Dogs that develop cancer spontaneously allow us to address the role of heritable risk factors and genes that influence prognosis (how the tumor behaves and how it will affect the patient’s overall health and survival time) and prediction (how well the animals respond to treatment). Practically everything we learn from the dogs will also be applicable to cancer in people. Cultured cells and laboratory animal experiments allow us to explore the precise mechanisms and pathways that are modulated by the genes in question.

Cancer Gene Therapy and Immunotherapy - Our goals are to continue development of treatment strategies that are effective and have no or acceptable toxicity. We have seen incredible advances in cancer therapy in the past two decades. In fact, some cancer patients (human and animal alike) are effectively cured of their disease by the use of surgery, chemotherapy, or radiation therapy alone or in combination. However, many patients still die from their disease and even the most advanced chemotherapy and radiation therapy strategies have some toxic side effects. Moreover, these treatments can provoke selection of resistant cells that eventually spread to other organs (metastasis). Tumors that spread to vital organs and impede their normal function are responsible for most cancer deaths. An appealing aspect of cancer gene therapy and immunotherapy is precisely the possibility to destroy such tumors, by restoring normal gene function to malignant cells, or by harnessing the immune system to destroy metastatic tumors before they become established in other organs.

Selected Publications:

• Baksh S, Widlund HR, Frazer-Abel AA, Du J, Fosmire S, Fisher DE, DeCaprio JA, Modiano JF, Burakoff SJ. (2002). NFATc2-mediated repression of cyclin-dependent kinase 4 expression. Mol Cell, 10, 1071-1081
• Bianco SR, Sun J, Fosmire SP, Hance K, Padilla M, Ritt MG, Getzy D, Duke RC, Withrow S, Lana S, Matthiesen DT, Dow S, Bellgrau D, Cutter G, Helfand SC, Modiano JF. (2003). Enhancing anti-melanoma immune responses through apoptosis. Cancer Gene Ther, 10, 726-736
• Frazer-Abel AA, Baksh S, Fosmire SP, Willis D, Pierce AM, Meylemans H, Linthicum DS, Coons T, Burakoff SJ, Bellgrau D, Modiano JF. (2004). Nicotine activates NFATc2 and prevents cell cycle entry in T cells. J Pharmacol Exp Ther, 311, 758-769
• Modiano JF, Breen M, Burnett RC, Parker HG, Inusah S, Thomas R, Avery PR, Lindblad-Toh K, Ostrander EA, Cutter G, Avery AC. (2005). Distinct prevalence of B-cell and T-cell lymphoproliferative diseases among dog breeds indicates heritable risk. Cancer Res, 65, 5654-5661
• Lamerato-Kozicki AR, Helm K, Jubala CM, Modiano JF. (2006). Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation. Exp Hematol, 34 (7), 870-878

View of Recent Publications in PubMed

Awards & Honors

• 1994 Individual National Research Service Award (NRSA), National Heart Lung and Blood Institute, National Institutes of Health
• 1994 Clinical Investigator Development Award (CIDA), National Heart Lung and Blood Institute, National Institutes of Health
• 1998 Technical Workshop Travel Award, National Institute of Aging, National Institutes of Health, Philadelphia, PA
• 1998 American Association of Immunologists Travel Award, 10th International Congress of Immunology, New Delhi, India (declined)
• 1999 Shannon Award, National Cancer Institute, National Institutes of Health
• 2002 Research Scholar Award, American Cancer Society
• 2004, 2006 Member (ad hoc), Cancer Molecular Pathology (CAMP) Study Section, Center for Scientific Review, National Institutes of Health
• 2005-2009 Member, NCI-F Study Section, National Cancer Institute, National Institutes of Health