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Research at Mass General
The long term goal of our research is to understand the regulation and execution of apoptosis, using the powerful genetic and molecular techniques available in Drosophila. Initially, we identified several genes that act as central regulators of apoptosis. The genes: reaper, grim, hid and sickle serve as an integration point for signaling pathways that regulate developmental apoptosis, and apoptosis in response to damage. Each of these genes is responsive to a different array of upstream transcription and posttranslational regulators, and apoptosis of a particular cell is regulated by multiple upstream pathways. We are concentrating on the death of neural stem cells during development as a model for understanding how this apoptosis is specified. We have also recently focused on the developmental consequences of blocking neural stem cell death.
One strategy we have used is to screen for mutations that modify the ability of rpr, grim and hid to induce apoptosis. Among the genes we have identified with this strategy are a Drosophila homologue of the Inhibitor of Apoptosis Protein family of antiapoptotic proteins (DIAP1), and the Ras gene. We recently completed a structure/function analysis of the IAP homologue, looking at the effects of various mutations on the ability of these proteins to protect against apoptosis. Further work on Ras demonstrated that the Drosophila EGF receptor, acting through the Ras/MAPK pathway plays an important role in regulating apoptosis in the developing animal, and that the proapoptotic gene hid is an important target of EGF antiapoptotic activity.
The terminal event of apoptosis is the engulfment of cell corpses by macrophages. The Croquemort protein (CRQ), a member of the CD36 family of scavenger receptors, is expressed on macrophages in the developing Drosophila embryo. We have shown that CRQ is essential for the efficient engulfment of apoptotic cells, and have begun to explore how this protein participates in the engulfment of cell corpses, how it is regulated, and what the ligand might be on the cell corpse. We have completed a screen for mutations that show defects in engulfment of apoptotic corpses, and expect to identify many new genes important for this process.
In summary, we expect that our work will provide important insights into many aspects of apoptosis, from the initiation of the apoptotic program to the final disposal of the corpse, both in Drosophila and in mammalian systems.
View my publications at PubMed 1. White K, Grether ME, Abrams JM, Young L, Farrell K, Steller H. GeneticControl of Programmed Cell Death in Drosophila. Science 1994; 264:677-683.
2. White K, Tahaoglu E, Steller H. Cell Killing by Drosophila reaper. Science1996; 271:805-807.
3. Kurada P, and White K. Ras promotes cell survival in Drosophila bydown-regulating hid expression. Cell 1998; 95:319-329.
4. Franc NC, Heitzler P, Ezekowitz RAB, White K. Requirement for croquemort inphagocytosis of apoptotic cells in Drosophila. Science 1999; 284:1994-1998.
5. Lisi S, Mazzon I, White K. Diverse domains of DIAP1/THREAD are required toinhibit apoptosis induced by REAPER and HID in Drosophila. Genetics2000; 154:669-678.
6. Peterson C, Carney GE, Taylor B, White K. Reaper is required forneuroblast apoptosis during Drosophila development. Development 2002;129:1467-1476.
7. Yokokura T, Dresnek, D, Huseinovic N, Lisi S, Abdelwahid E, Bangs P,White K. Dissection of DIAP1 functional domains via a mutant replacementstrategy, J Biol Chem 2004; 279:52603-52612.
Cutaneous Biology Research Center
Directions to Charlestown Navy Yard MGH East - Building 149
From Storrow Drive
From the end of Storrow Drive (Leverett Circle) keep to the far right and take a sharp right (do not go up the ramp), and continue beneath the underpass one quarter mile to the light.
Turn left onto Causeway street under the elevated subway tracks. The Fleet Center will be on your left, the North Station T station on your right.
One block past the Garden, turn left on to N. Washington Street, passing over the Charlestown Bridge.
At the first light after the bridge, take a right. Go through three traffic control lights.
At the fourth light, turn right into Navy Yard (Gate 5 - 13th Street). To park, take first left onto Fifth Avenue. Building 149 is one block on the right.
The parking garage entrance is on the right about half way down the block.
Take the Mass Pike (I-90) to I-93 North (Exit 24B)
Take the Storrow Drive Exit (Exit 26)Stay in the left lane once getting on the exit ramp. Follow signs for North Station/Leverett Circle Go through 1 light and take left at the 2nd light (almost immediately after the first)
Get immediately into the right lane
Take a right at the light onto Route 28N
The Museum of Science will be on your left
Take a right at the 3rd light (there is a sign at the corner for Charlestown)
Go over the bridge and get in the right lane (City Square)
Take your 1st right and get into the left lane
Turn left at the 2nd light (immediately before Charlestown Bridge, at City Square) onto Chelsea Street (If you go over bridge, you've gone too far).
Go through three traffic control lights
At the 4th light, turn right into the Navy Yard (Gate 5 - 13th Street).
To park, take first left onto Fifth Avenue. Parking Garage entrance is on the right above half way down the block. Building 149 is one block on the right once you turn into Gate 5. Building 149 is also connected to the parking garage.
Take Exit 28 (Charlestown/Sullivan Square).
At the end of the exit where the read forks stay to the right and proceed past the bus terminal to the rotary at Sullivan Square.
Go halfway around the rotary towards Charlestown (the Schrafts building with a large American flag on top of it will be on your left).
Cross the railroad tracks and take a left at the fire station onto Medford Street.
At the end of Medford street turn left onto Chelsea Street and make an immediate right into the Navy Yard.
The MGH East Research Building (Bldg. 149) will be on the right and is connected to the parking garage by overhead walkways.
Direct the driver to the MGH East, Building 149 in the Charlestown Navy Yard.
The CBRC is on the 3rd Floor of Building 149.By Public Transportation & the MGH/Partners Shuttle
Take the T (Green Line) to North Station
Take the MGH/Partners Shuttle bus to the Charlestown Navy Yard MGH East Research Building (Building 149).
The CBRC is on the 3rd Floor.
The MGH/Partners Shuttle bus leaves MGH on Blossom Street and stops at North Station on Canal Street by the Green Line T stop. The shuttle goes every 15 minutes during working hours. (Less often on the weekends and holidays).
To get to the CBRC, take the first set of elevators to the left of the main entrance by the Security Desk to the third floor. You may need to check in with security on the main level of Building 149.
From the elevator, exit to the East to the CBRC offices, or in the opposite direction for the laboratories.
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