Anthony Orth, Ph.D.
Group Leader
Our Gene Core is combining the intrigue of basic genomic research with the excitement of the latest technologies in three lines of investigation.
On the technology side, we identify, test, and deploy systems permitting viral delivery of shRNAs and cDNAs. This enables the screening of primary, difficult-to-transfect human or mouse cell lines and primary cells, supplementing our already broad collections of cDNAs, shRNAs, and siRNAs for transfection-mediated experiments. To generate and maintain our libraries, which now contain a total of over 250,000 unique entities, we employ an advanced suite of automated robotic instruments, permitting high throughput rearraying and preparation of ready-to-assay materials. Our current libraries include:
Plasmid cDNA collections
| • Origene unique human cDNA |
19,823 |
|
• MGC unique human cDNA |
20,739 |
|
• MGC unique mouse cDNA |
15,652 |
|
• Anti-human 5k druggable shRNA (random) |
14,763 |
|
• Anti-human 5k druggable shRNA (poolable ) |
14,411 |
|
• Anti-human 474 non-coding shRNA |
775 |
|
• Anti-mouse 616 kinase shRNA |
2,777 |
|
• GNF human ORFs |
1,441 |
|
• MGC mouse+human Kinase cDNA |
847 |
Viral cDNA collections
| • Anti-human 5k druggable shRNA in lenti | 14,398 |
| • Anti-mouse kinase shRNA in lenti | 2,552 |
| • MGC mouse/human cDNA in retro | 8,412 |
siRNA collections
| • GNF anti-human 5k druggable siRNA | 10,180 |
| • Novartis anti-human 5k druggable siRNA | 9,736 |
| • FGA anti-human 24k whole genome siRNA | 49,276 |
| • FGA anti-human 24k whole genome siRNA pooled | 24,672 |
Basic Research
We are interested in genes that play a role in the development or mechanisms of type II diabetes. To date, we have met with success screening for genes which, when over-expressed, block activation of an insulin-sensitive reporter by insulin. Putative hits are being further characterized for their ability to phosphorylate a key pathway kinase, mediate translocation of Glut4 constructs, potentiate adipogenesis, and modulate other aspects of canonical insulin signaling.
Selected Publications
- Luesch H, Chanda SK, Raya RM, DeJesus PD, Orth AP, Walker JR, Izpisua Belmonte JC, Schultz PG. A functional genomics approach to the mode of action of apratoxin A. Nat Chem Biol 2006;2(3):158-67.
- Cho CY, Koo SH, Wang Y, Callaway S, Hedrick S, Mak PA, Orth AP, Peters EC, Saez E, Montminy M, et al. Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling. Cell Metab 2006;3(5):367-78.
- Bandell M, Dubin AE, Petrus MJ, Orth A, Mathur J, Hwang SW, Patapoutian A. High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol. Nat Neurosci 2006;9(4):493-500.
- Willingham AT, Orth AP, Batalov S, Peters EC, Wen BG, Aza-Blanc P, Hogenesch JB, Schultz PG. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 2005;309(5740):1570-3.
