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Gideon Dreyfuss, Ph.D.
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Isaac Norris Professor
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Department: Biochemistry and Biophysics
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Graduate Group Affiliations
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b
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6b
- Cell and Molecular Biology 3a
- Biology e
1d
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Contact information
3d
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1d
3d
415 Curie Blvd.
4d Clinical Research Building, Room 328,
Philadelphia, PA 19104-6148
26
4d Clinical Research Building, Room 328,
Philadelphia, PA 19104-6148
30
Office: (215) 898-0398
32 Fax: 215-573-2000
24
91
32 Fax: 215-573-2000
24
Email:
GDREYFUSS@HHMI.UPENN.EDU
12
GDREYFUSS@HHMI.UPENN.EDU
18
Publications
23 a
3
2
4
b
1f
23 a
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Education:
21 a B.Sc. 16 (Chemistry) c
41 The Hebrew University, Jerusalem, Israel, 1973.
21 a M.Sc. 19 (Biochemistry) c
3e Tel Aviv University, Tel Aviv, Israel, 1975.
21 a Ph.D. 21 (Biological Chemistry) c
2b Harvard University, 1978.
c
3
27
21 a B.Sc. 16 (Chemistry) c
41 The Hebrew University, Jerusalem, Israel, 1973.
21 a M.Sc. 19 (Biochemistry) c
3e Tel Aviv University, Tel Aviv, Israel, 1975.
21 a Ph.D. 21 (Biological Chemistry) c
2b Harvard University, 1978.
c
Links
7d Search PubMed for articles
70 Dreyfuss Lab homepage
78 Dreyfuss HHMI webpage
5b Biochemistry and Molecular Biophysics graduate group faculty webpage.
c
5
3
3
90
Permanent link7d Search PubMed for articles
70 Dreyfuss Lab homepage
78 Dreyfuss HHMI webpage
5b Biochemistry and Molecular Biophysics graduate group faculty webpage.
c
2 29
21
1e
1d
24
5e
35 -The Survival of Motor Neurons (SMN) complex
1e -RNA-binding proteins
39 -Spinal Muscular Atrophy/neurogenerative disease
3f -Assembly and transport of RNA-protein (RNP) complexes
24 -High throughput screening.
8
97 Key words: RNA, RNPs (ribonucleoproteins), SMN, Spinal Muscular Atrophy, High throughput screening, neurodegneration, nuclear transport.
8
26 Description of Research
627 The functional forms of RNAs in cells are ribonucleoprotein (RNP) complexes, the complexes that contain RNAs and their associated RNA-binding proteins. The RNP proteins profoundly influence every aspect of the biogenesis and function of the RNAs, including their processing, transport, localization, interactions, translation, and stability. We have been particularly interested in RNA-binding proteins and the complexes they form with pre-mRNAs (hnRNAs) and mRNAs. We identified and characterized the major proteins that interact with these RNAs (hnRNPs and mRNPs) and studied them in detail. These studies led to the identification of RNA-binding domains, novel nuclear structures and transport pathways, and opened up new areas of research on important human genetic diseases, including spinal muscular atrophy (SMA) and fragile X syndrome. Over the past several years we have been involved in the discovery of a complex of proteins that forms on mRNAs in the wake of the splicing of pre-mRNAs at the site of exon ligation. This complex, the exon-junction complex (EJC), is comprised of several proteins, (including Y14, mago, RNP S1, Upf3, ALY, Srm160, eIF4A3) some of which remain associated with the mRNA after it is exported from the nucleus to the cytoplam. The EJC proteins play important roles in the export of mRNAs as well as in their translation and localization, and they serve as a marker that allows cells to define the authentic termination codon and thus detect and destroy mRNAs that contain pre-mature termination codons (nonsense-mediated decay).
8
5b9 We are now particularly interested in a large multi-protein complex, the Survival of Motor Neurons Protein (SMN) complex, that we described over the last few years. The SMN compex functions as an assembly machine for spliceosomal small nuclear ribonucleoproteins (snRNPs) and possibly other RNPs, in pre-mRNA splicing, and in the assembly of mRNA factories (transcriptosomes). The discovery of this kind of activity was unexpected because several RNPs have been known to have the capacity to self-assemble from purified components in vitro. In cells, however, such assembly processes would probably be inefficient and prone to inaccuracies without the assistance of the SMN complex. It casts a new light on how RNA-protein interactions, the key to post-transcriptional gene expression, are orchestrated. Some of our main objectives are to determine the complete composition, interactions, structure, and functions of the SMN complex. To assemble RNPs, the SMN complex must recognize and bring together their protein and RNA components. We are engaged in determining the specific features in the RNAs and the proteins that mediate their binding to the SMN complex. SMN is essential for viability of all cells, but reduced levels of this protein cause Spinal Muscular Atrophy (SMA), a common motor neuron degenerative disease. From studies of the SMN complex emerge new approaches for discovering potential therapeutics for SMA that we are currently pursuing.
8
2ab Another major current effort is the use of lab automation and robotics for high-throughput screening (HTS) of libraries of small molecules in search of potential therapeutics for SMA. In particular, using cell-based assays we developed, we are searching for compounds that may alleviate the deficiency in the SMN protein and increase the amount of functional SMN protein in cells, as well as for compounds that may improve the survival of cells at low SMN. We have identified promising leads and are studying them further. We are also using HTS as a general approach for discovery of biologically active small molecule effectors of several pathways that we are interested in.
8
21 Rotation Projects
3b Please visit the lab to discuss available projects.
8
1d Lab personnel:
35 Jennifer Bachorik, Ph.D. - Research Associate
2d Mike Berg, Ph.D. - Research Associate
25 E. Anna Bridges - Lab Manager
31 Sungchan Cho, Ph.D. - Postdoctoral Fellow
36 Kazuhiro Fukumura, Ph.D. - Postdoctoral Fellow
31 Tina Glisovic, Ph.D. - Research Associate
33 Jennifer Jackson - Administrative Assistant
3b Daisuke Kaida, Ph.D. - Postdoctoral Research Fellow
30 Mumtaz Kasim, Ph.D. - Research Associate
33 Isabela Oliva, Ph.D. - Research Specialist
3d Anna Maria Pinto, M.D. - Postdoctoral Research Fellow
3a Ria Sotiriou, Ph.D. - Postdoctoral Research Fellow
2c Lili Wan, Ph.D. - Research Associate
30 Congli Wang, Ph.D. - Research Specialist
31 Jeongsik Yong, Ph.D. - Research Associate
2f Ihab Younis, Ph.D. - Research Associate
30 Zhenxi Zhang, Ph.D. - Research Associate
31 Rundong Zhang, Ph.D. - Research Specialist
26 7 1d 1f
27
Description of Research Expertise
2b Research Interests35 -The Survival of Motor Neurons (SMN) complex
1e -RNA-binding proteins
39 -Spinal Muscular Atrophy/neurogenerative disease
3f -Assembly and transport of RNA-protein (RNP) complexes
24 -High throughput screening.
8
97 Key words: RNA, RNPs (ribonucleoproteins), SMN, Spinal Muscular Atrophy, High throughput screening, neurodegneration, nuclear transport.
8
26 Description of Research
627 The functional forms of RNAs in cells are ribonucleoprotein (RNP) complexes, the complexes that contain RNAs and their associated RNA-binding proteins. The RNP proteins profoundly influence every aspect of the biogenesis and function of the RNAs, including their processing, transport, localization, interactions, translation, and stability. We have been particularly interested in RNA-binding proteins and the complexes they form with pre-mRNAs (hnRNAs) and mRNAs. We identified and characterized the major proteins that interact with these RNAs (hnRNPs and mRNPs) and studied them in detail. These studies led to the identification of RNA-binding domains, novel nuclear structures and transport pathways, and opened up new areas of research on important human genetic diseases, including spinal muscular atrophy (SMA) and fragile X syndrome. Over the past several years we have been involved in the discovery of a complex of proteins that forms on mRNAs in the wake of the splicing of pre-mRNAs at the site of exon ligation. This complex, the exon-junction complex (EJC), is comprised of several proteins, (including Y14, mago, RNP S1, Upf3, ALY, Srm160, eIF4A3) some of which remain associated with the mRNA after it is exported from the nucleus to the cytoplam. The EJC proteins play important roles in the export of mRNAs as well as in their translation and localization, and they serve as a marker that allows cells to define the authentic termination codon and thus detect and destroy mRNAs that contain pre-mature termination codons (nonsense-mediated decay).
8
5b9 We are now particularly interested in a large multi-protein complex, the Survival of Motor Neurons Protein (SMN) complex, that we described over the last few years. The SMN compex functions as an assembly machine for spliceosomal small nuclear ribonucleoproteins (snRNPs) and possibly other RNPs, in pre-mRNA splicing, and in the assembly of mRNA factories (transcriptosomes). The discovery of this kind of activity was unexpected because several RNPs have been known to have the capacity to self-assemble from purified components in vitro. In cells, however, such assembly processes would probably be inefficient and prone to inaccuracies without the assistance of the SMN complex. It casts a new light on how RNA-protein interactions, the key to post-transcriptional gene expression, are orchestrated. Some of our main objectives are to determine the complete composition, interactions, structure, and functions of the SMN complex. To assemble RNPs, the SMN complex must recognize and bring together their protein and RNA components. We are engaged in determining the specific features in the RNAs and the proteins that mediate their binding to the SMN complex. SMN is essential for viability of all cells, but reduced levels of this protein cause Spinal Muscular Atrophy (SMA), a common motor neuron degenerative disease. From studies of the SMN complex emerge new approaches for discovering potential therapeutics for SMA that we are currently pursuing.
8
2ab Another major current effort is the use of lab automation and robotics for high-throughput screening (HTS) of libraries of small molecules in search of potential therapeutics for SMA. In particular, using cell-based assays we developed, we are searching for compounds that may alleviate the deficiency in the SMN protein and increase the amount of functional SMN protein in cells, as well as for compounds that may improve the survival of cells at low SMN. We have identified promising leads and are studying them further. We are also using HTS as a general approach for discovery of biologically active small molecule effectors of several pathways that we are interested in.
8
21 Rotation Projects
3b Please visit the lab to discuss available projects.
8
1d Lab personnel:
35 Jennifer Bachorik, Ph.D. - Research Associate
2d Mike Berg, Ph.D. - Research Associate
25 E. Anna Bridges - Lab Manager
31 Sungchan Cho, Ph.D. - Postdoctoral Fellow
36 Kazuhiro Fukumura, Ph.D. - Postdoctoral Fellow
31 Tina Glisovic, Ph.D. - Research Associate
33 Jennifer Jackson - Administrative Assistant
3b Daisuke Kaida, Ph.D. - Postdoctoral Research Fellow
30 Mumtaz Kasim, Ph.D. - Research Associate
33 Isabela Oliva, Ph.D. - Research Specialist
3d Anna Maria Pinto, M.D. - Postdoctoral Research Fellow
3a Ria Sotiriou, Ph.D. - Postdoctoral Research Fellow
2c Lili Wan, Ph.D. - Research Associate
30 Congli Wang, Ph.D. - Research Specialist
31 Jeongsik Yong, Ph.D. - Research Associate
2f Ihab Younis, Ph.D. - Research Associate
30 Zhenxi Zhang, Ph.D. - Research Associate
31 Rundong Zhang, Ph.D. - Research Specialist
26 7 1d 1f
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