BBS Faculty Member - Kristin White

Kristin White

Department of Cell Biology

Massachusetts General Hospital East
Cutaneous Biology Research Center
Charlestown Navy Yard 3
Charlestown, MA 02129
Tel: 617-726-4440
Fax: 617-726-4453
Email: kristin.white@cbrc2.mgh.harvard.edu



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 the 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 also undertook 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. Recently we showed that the Rpr and Hid proteins can localize to mitochondria, resulting in mitochondrial permeabilization. We are now focused on understanding the mechanisms underlying this activity, to identify the conserved role of mitochondria in programmed cell death.



Last Update: 6/19/2014



Publications

Kornbluth, S, White, K. Apoptosis in Drosophila: Neither Fish nor Fowl (nor man, nor worm), J. Cell Sci, 2005; 118:1779-1787.

Yokokura T, Dresnek, D, Huseinovic N, Lisi S, Abdelwahid E, Bangs P, White K. Dissection of DIAP1 functional domains via a mutant replacement strategy, J Biol Chem, 2004; 279:52603-52612.

Abdelwahid E, Yokokura T, Krieser RJ, Balasundaram S, Fowle WH, White K. Mitochondrial disruption in Drosophila apoptosis. Dev Cell, 2007, 12:793-806.

Krieser RJ, Moore FE, Dresnek D, Pellock BJ, Patel R, Huang A, Brachmann C, White K. The Drosophila homolog of the putative phosphatidylserine receptor functions to inhibit apoptosis. Development, 2007, 134:2707-2414.

Tan Y*,Yamada-Mabuchi M*, Arya R, St. Pierre S, Tang W, Tosa M, Brachmann C and White K, Coordinated expression of cell death genes regulates neuroblast apoptosis, Development, 2011, 138: 2197-2206.

Abdelwahid E, Rolland S, Teng X, Conradt B, Hardwick JM, White K, Mitochondrial involvement in cell death of lower eukaryotes, BBA, 2011; 1813:597-607.



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