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Frederic G. Barr, MD, PhD
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Adjunct Professor of Pathology and Laboratory Medicine
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Department: Pathology and Laboratory Medicine
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Contact information
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10 Center Drive, Room 3B55, MSC1500
Bethesda, MD 20892
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Bethesda, MD 20892
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Office: (301) 594-3780
34 Fax: (301) 480-0853
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34 Fax: (301) 480-0853
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Email:
barrfg@mail.nih.gov
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barrfg@mail.nih.gov
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Publications
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Links
159 Search PubMed for articles
7c NCI Laboratory of Pathology
98 Penn Cell and Molecular Biology graduate group
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159 Search PubMed for articles
7c NCI Laboratory of Pathology
98 Penn Cell and Molecular Biology graduate group
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Education:
21 9 B.A. 16 (Chemistry) c
29 Williams College, 1980.
21 9 M.D. c
39 Washington University, St. Louis, 1987.
21 a Ph.D. 1e (Molecular Biology) c
2e Washington University, 1987.
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Permanent link21 9 B.A. 16 (Chemistry) c
29 Williams College, 1980.
21 9 M.D. c
39 Washington University, St. Louis, 1987.
21 a Ph.D. 1e (Molecular Biology) c
2e Washington University, 1987.
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58a To complement these studies of the fusion protein, my research laboratory is also investigating additional changes that occur during the development of ARMS. Our functional studies indicated that the PAX3-FOXO1 fusion protein must cooperate with other changes to cause normal cells to become tumorigenic. To search for such events in ARMS, my laboratory performed a large screen of DNA copy number changes on all chromosomes in the cancer cells, and participated in a large multi-laboratory next generation sequencing project that searched for small DNA changes throughout the ARMS genome. These studies revealed that, though there are few if any recurrent small DNA changes in ARMS, there are frequent changes in which chromosome regions increase in copy number in a process known as amplification. These amplification events will increase the production of cellular proteins that contribute to cancer formation. Current studies are identifying the proteins encoded by these amplified regions and the specific function of these proteins in ARMS. Finally, my research laboratory is now performing another genome-wide screen to investigate an additional set of DNA changes that occur at the level of methylation, a type of DNA modification. These methylation changes will affect whether a gene is expressed in cells by altering how the DNA packages with nuclear proteins to form the complex known as chromatin.
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30a To investigate the clinical utility of translocations, amplification and other DNA changes, I have also established a translational research program exploring the role of these molecular markers in the diagnosis, prognosis, and management of pediatric sarcomas. These studies are addressing both molecular approaches for detection of these changes in tumors and the correlation of these molecular findings with clinical characteristics, including patient outcome. Many of these studies are performed as part of the larger research program of the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. The findings of these clinical research studies are now being incorporated into the next set of clinical trials conducted by the Soft Tissue Sarcoma Committee.
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Description of Research Expertise
44c During the last two decades, my research laboratory has focused on studies to unravel the fundamental events responsible for the aggressive pediatric soft tissue cancer alveolar rhabdomyosarcoma (ARMS). After chromosome studies of this cancer identified translocations (exchanges of genetic material) between chromosome 13 and either chromosome 2 or chromosome 1, my laboratory identified that these translocations break within the PAX3 gene on chromosome 2 or the PAX7 gene on chromosome 1, and join part of these genes with part of the FOXO1 gene on chromosome 13. This process results in the formation of a PAX3-FOXO1 or PAX7-FOXO1 fusion protein. Numerous studies have shown that this fusion protein is essential for the development of ARMS. My laboratory’s more recent studies are investigating how these fusion proteins are made and function in the cancer cells, and are exploring how to manipulate fusion protein expression and function in ARMS cells with the ultimate goal of developing novel strategies for targeting these fusion proteins and thereby treating this cancer.8
58a To complement these studies of the fusion protein, my research laboratory is also investigating additional changes that occur during the development of ARMS. Our functional studies indicated that the PAX3-FOXO1 fusion protein must cooperate with other changes to cause normal cells to become tumorigenic. To search for such events in ARMS, my laboratory performed a large screen of DNA copy number changes on all chromosomes in the cancer cells, and participated in a large multi-laboratory next generation sequencing project that searched for small DNA changes throughout the ARMS genome. These studies revealed that, though there are few if any recurrent small DNA changes in ARMS, there are frequent changes in which chromosome regions increase in copy number in a process known as amplification. These amplification events will increase the production of cellular proteins that contribute to cancer formation. Current studies are identifying the proteins encoded by these amplified regions and the specific function of these proteins in ARMS. Finally, my research laboratory is now performing another genome-wide screen to investigate an additional set of DNA changes that occur at the level of methylation, a type of DNA modification. These methylation changes will affect whether a gene is expressed in cells by altering how the DNA packages with nuclear proteins to form the complex known as chromatin.
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30a To investigate the clinical utility of translocations, amplification and other DNA changes, I have also established a translational research program exploring the role of these molecular markers in the diagnosis, prognosis, and management of pediatric sarcomas. These studies are addressing both molecular approaches for detection of these changes in tumors and the correlation of these molecular findings with clinical characteristics, including patient outcome. Many of these studies are performed as part of the larger research program of the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. The findings of these clinical research studies are now being incorporated into the next set of clinical trials conducted by the Soft Tissue Sarcoma Committee.
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Description of Clinical Expertise
2d molecular diagnosis of cancer1a 29
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169 Du, S., Lawrence, E.J., Strzelecki, D., Rajput, P., Xia, S.J., Gottesman, D.M., Barr, F.G. : Co-expression of alternatively spliced forms of PAX3, PAX7, PAX3-FKHR, and PAX7-FKHR with distinct DNA binding and transactivation properties in rhabdomyosarcoma. Int. J. Cancer 115: 85-92, 2005.
117 Blandford, M., Barr, F.G., Lynch, J.C., Randall, R.L., Capecchi, M.R., Keller, C.: Rhabdomyosarcomas utilize developmental myogenic growth factors for disease advantage. Ped. Blood Cancer 46: 329-38, 2006.
f7 Mercado, G.E., Barr, F.G.: : Looking downstream of sarcoma-associated chimeric transcription factors - When is a target really a target? Cancer Biol. Ther. 4: 456-458, 2005.
d8 Xia, S.J., Barr F.G.: Oncogenic transcription factors resulting from chromosome translocations in sarcomas. Eur. J. Cancer 41: 2513-2527, 2005.
cf Zhang, P.J., Pawel, B., Pasha, T., Barr, F.G. : D2-40 is a useful marker for subtyping rhabdomyosarcoma. Modern Pathol. 18: 23A, 2005.
109 Lae, M., Edgar, M., Chuai, S., Olshen, A.B., Pawel, B.R., Barr, F.G., Ladanyi, M.: Global gene expression profiling of alveolar and embryonal rhabdomyosarcoma. Modern Pathol. 18: 305A, 2005.
142 Nishio, J., Althof, P., Bailey, J., Zhou, M,. Neff, J.R., Barr, F., Parham, D., Qualman, S., Bridge, J.A. : Use of FISH on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma (ARMS). Modern Pathol. 18: 305A-306A, 2005.
147 Mercado, G.E., Barr, F.G., Zhang, P.J.L., Pawel, B.R.: Identification of downstream targets of the PAX3-FKHR fusion oncoprotein that are differentially expressed between alveolar and embryonal rhabdomyosarcoma. Proc. Am. Assoc. Cancer Res. 46: 456, 2005.
ec Xia, S.J., Barr, F.G.: The paired-box domain of the fusion oncoprotein PAX3-FKHR suppressed oncogenic activity. Proc. Am. Assoc. Cancer Res. 46:: 1439-1440, 2005.
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Selected Publications
175 Zhang, P.J. Goldblum, J.R., Pawel, B.R., Pasha, T., Fisher, C., Barr, F.G.: PDGF-A, PDGF-Rb, TGFb3 and bone morphogenic protein-4 in desmoplastic small round cell tumors with EWS-WT1 gene fusion product and their role in stromal desmoplasia:an immunohistochemical study. Modern Path. 18: 382-7, 2005.169 Du, S., Lawrence, E.J., Strzelecki, D., Rajput, P., Xia, S.J., Gottesman, D.M., Barr, F.G. : Co-expression of alternatively spliced forms of PAX3, PAX7, PAX3-FKHR, and PAX7-FKHR with distinct DNA binding and transactivation properties in rhabdomyosarcoma. Int. J. Cancer 115: 85-92, 2005.
117 Blandford, M., Barr, F.G., Lynch, J.C., Randall, R.L., Capecchi, M.R., Keller, C.: Rhabdomyosarcomas utilize developmental myogenic growth factors for disease advantage. Ped. Blood Cancer 46: 329-38, 2006.
f7 Mercado, G.E., Barr, F.G.: : Looking downstream of sarcoma-associated chimeric transcription factors - When is a target really a target? Cancer Biol. Ther. 4: 456-458, 2005.
d8 Xia, S.J., Barr F.G.: Oncogenic transcription factors resulting from chromosome translocations in sarcomas. Eur. J. Cancer 41: 2513-2527, 2005.
cf Zhang, P.J., Pawel, B., Pasha, T., Barr, F.G. : D2-40 is a useful marker for subtyping rhabdomyosarcoma. Modern Pathol. 18: 23A, 2005.
109 Lae, M., Edgar, M., Chuai, S., Olshen, A.B., Pawel, B.R., Barr, F.G., Ladanyi, M.: Global gene expression profiling of alveolar and embryonal rhabdomyosarcoma. Modern Pathol. 18: 305A, 2005.
142 Nishio, J., Althof, P., Bailey, J., Zhou, M,. Neff, J.R., Barr, F., Parham, D., Qualman, S., Bridge, J.A. : Use of FISH on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma (ARMS). Modern Pathol. 18: 305A-306A, 2005.
147 Mercado, G.E., Barr, F.G., Zhang, P.J.L., Pawel, B.R.: Identification of downstream targets of the PAX3-FKHR fusion oncoprotein that are differentially expressed between alveolar and embryonal rhabdomyosarcoma. Proc. Am. Assoc. Cancer Res. 46: 456, 2005.
ec Xia, S.J., Barr, F.G.: The paired-box domain of the fusion oncoprotein PAX3-FKHR suppressed oncogenic activity. Proc. Am. Assoc. Cancer Res. 46:: 1439-1440, 2005.
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