Thomas Neufeld, PhD

Research Interests:

The Neufeld lab is interested in the basic mechanisms of cell growth control. They use the fruit fly Drosophila as a model system to investigate signaling pathways and cellular functions that regulate growth. The goal of their research is to understand how signals that control cell growth, such as nutrient conditions and growth factors, are connected to growth-promoting cellular processes such as nutrient uptake and biosynthesis.

They focus on the target of rapamycin (TOR) protein kinases, which are central regulators of cell growth whose function is conserved from yeast to plants to mammals.  TOR activity is controlled by nutrient levels, cellular energy state, and growth factors such as insulin, and in turn TOR controls multiple cellular functions critical for growth. Inappropriate activation of TOR signaling underlies a number of growth-related genetic diseases including cancer. In the lab, the approach is to identify mutations in genes involved in TOR signaling, and to characterize their function using multiple cellular and genetic assays.

A second, related area of the lab's research centers on the degradative process known as autophagy. This process, which is controlled by the TOR pathway and induced by starvation, involves the non-selective engulfment and degradation of cytoplasm within the lysosome. Through autophagy, macromolecules and entire organelles are recycled into amino acids, lipids, and other simple molecules, thus supplying the cell with an internal source of nutrients under starvation conditions. Although autophagy has been understood morphologically for many years, the past decade has seen a new surge of interest in autophagy due to the recent discovery of approximately 20 “ATG” genes that regulate autophagy, and to the discovery that defects in autophagy are involved in aging, neurodegeneration, and cancer. The lab hopes to use the genetic tools available in Drosophila to define the functions and regulation of autophagy.

Selected Publications:

Kim, E.#, Goraksha, P.#, Neufeld, T. P.*, Guan, K.-L.* Regulation of TORC1 by Rag GTPases in nutrient response.  Nature Cell Biology, 10(8): 935-45. PMID: 18604198 #equal contributions; *co-corresponding authors

Ling D, Song HJ, Garza D,Neufeld TP, Salvaterra PM.  2009.  Abeta42-induced neurodegeneration via an age-dependent autophagic-lysosomal injury in Drosophila.  PLoS ONE, 4(1): e4201. PMID: 19145255

Arsham AM, Neufeld TP. 2009 A genetic screen in Drosophila reveals novel cytoprotective functions of the autophagy-lysosome pathway.  PLoSONE, 4(6):e6068.

Chang YY, Neufeld TP.  2009.  An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Molecular Biology of the Cell, 20(7): 2004-14.  PMID: 19225150

Ling D, Song HJ, Garza D, Neufeld TP, Salvaterra PM.  2009.  Abeta42-induced neurodegeneration via an age-dependent autophagic-lysosomal injury in Drosophila.  PLoS ONE, 4(1): e4201. PMID: 19145255

Chang YY, Juhász G, Goraksha-Hicks P, Arsham AM, Mallin DR, Muller LK, Neufeld TP.  2009.  Nutrient-dependent regulation of autophagy through the target of rapamycin pathway.  Biochem Soc Trans. 37(1): 232-6. PMID: 19143638

Kim E, Goraksha-Hicks P, Neufeld TP, Guan KL.  2008.  Regulation of TORC1 by Rag GTPases in nutrient response.  Nature Cell Biology, 10(8): 935-45. PMID: 18604198

Meléndez A, Neufeld TP.  2008.  The cell biology of autophagy in metazoans: a developing story.  Development,135(14): 2347-60. PMID: 18567846

Juhász G, Hill JH, Yan Y, Sass M, Baehrecke EH, Backer JM, Neufeld TP.  2008.  The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila.  Journal of Cell Biology, 181(4): 655-66.  PMID: 18474623

Juhász G, Neufeld TP.  2008.  Experimental control and characterization of autophagy in Drosophila.  Methods in Molecular Biology, 445: 125-33. PMID: 18425447

Neufeld TP.  2008.  Genetic manipulation and monitoring of autophagy in Drosophila.  Methods in Enzymology, 451:653-67. PMID: 19185744

Neufeld TP, Baehrecke EH.  2008.  Eating on the fly: Function and regulation of autophagy during cell growth, survival and death in Drosophila.  Autophagy, 4(4): 1-6. PMID: 18319640

Juhász G, Erdi B, Sass M,  Neufeld TP.  2007.  Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes & Development, 21(23): 3061-6. PMID: 18056421

Juhász G, Puskas LG, Komonyi O, Erdi B, Maroy P, Neufeld TP, Sass M.  2007.  Gene expression profiling identifies FKBP39 as an inhibitor of autophagy in Drosophila. Cell Death and Differentiation, 14(6): 1181-90. PMID: 17363962

Knox S, Ge H, Dimitroff BD, Ren Y, Howe KA, Arsham AM, Easterday MC, Neufeld TP, O’Connor MB, Selleck SB.  2007.  Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance. PLoS ONE, 4:e375. PMID: 17440611

Scott RC, Juhasz G, Neufeld TP.  2007.  Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death.  Current Biology, 17(1): 1-11.  PMID: 17208179

Neufeld TP.  2007.  TOR regulation: sorting out the answers.  Cell Metabolism, 5(1): 3-5. PMID: 17189200

Arsham AM, Neufeld TP.  2006.  Thinking globally and acting locally with TOR.  Current Opinion in Cell Biology 18(6): 589-597. PMID: 17046229

Hennig KM, Colombani J, Neufeld TP.  2006.  TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. Journal of Cell Biology 173(6): 963-974. 16785324

Juhasz G, Neufeld TP.  2006. Autophagy: a forty year search for a missing membrane source.  PLoS Biology 4(2):e36. PMID: 16464128

Zhang Y, Billington CJ, Pan D, Neufeld TP.  2006. Drosophila Target of Rapamycin kinase functions as a multimer.  Genetics 172(1): 355-362. PMID: 16219781

Cygnar KD, GaoX, Pan D, Neufeld TP.  2005. The phosphatase subunit Tap42 functions independently of TOR to regulate cell division and survival in Drosophila.  Genetics 170: 733-740. PMID: 15802506

Scott RC, Schuldiner O, Neufeld TP.  2004.  Role and regulation of starvation-induced autophagy in the Drosophila fat body.  Developmental Cell 7: 167-178. PMID: 15296714

Neufeld TP.  2004.  Genetic analysis of TOR signaling in Drosophila. Current Topics in Microbiology and Immunology 279: 139-152. PMID: 14560956

Neufeld TP.  2003.  Body building: regulation of shape and size by PI3K/TOR signaling during development.  Mechanisms of Development 120:1283-1296. PMID: 14623438

Hennig KM, Neufeld TP.  2002.  Inhibition of cellular growth and proliferation by dTOR overexpression in Drosophila.  genesis 34:107-110. PMID: 12324961

Tang AH, Neufeld TP, Rubin GM, Müller HJ.  2001. Transcriptional regulation of cytoskeletal functions and segmentation by a novel maternal pair-rule gene, lilliputian.  Development 128:801-813. PMID: 11171404

Zhang H, Stallock JP, Ng JC, Reinhard C, Neufeld TP.  2000.  Regulation of cellular growth by the Drosophila target of rapamycin, dTOR.  Genes & Development 14:2712–2724. PMID: 11069888

Gao X, Neufeld TP, Pan D.  2000.  Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways.  Developmental Biology 221:404-18. PMID: 10790335

Weinkove D, Neufeld TP, Twardzik T, Waterfield MD,  Leevers SJ.  1999.  The Drosophila class IA PI3K and its adaptor are autonomously required for imaginal discs to achieve their normal cell size, cell number and organ size. Current Biology 9:1019-1029. PMID: 10508611

Neufeld TP, Edgar BA.  1998.  Connections between growth and the cell cycle.  Current Opinion in Cell Biology 10:784-790. PMID: 9914170

Neufeld TP, de la Cruz AFA, Johnston LA, Edgar BA.  1998.  Coordination of growth and cell division in the Drosophila wing.  Cell 93: 1183-1193. PMID: 9657151

To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
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