• Entomology
• BISI - BISI-Molecular & Cellular Biology (MOCB)
• BISI - BISI-Behavior, Ecology, Evolution, & Systematics (BEES)

How does a complex organism – composed of numerous differentiated cell types and integrated organ systems – develop from a fertilized egg? We are using the fruit fly, Drosophila melanogaster, as a model system to address this fundamental question of developmental biology. Our studies probe basic mechanisms underlying pattern formation, determination, differentiation and morphogenesis in animal development. The two major projects currently underway in the lab are summarized below. 

The first major project in the lab is to study how a group of master regulatory genes – the homeobox (Hox) genes – establishes the basic body plan of the fly during early embryogenesis. Hox genes specify cell fate and regional identity during animal development. These genes are structurally and functionally conserved throughout the animal kingdom: we and others have shown that Hox genes from mammals and flies are functionally equivalent in that mammalian Hox genes can mimic the function of fly homologs when expressed as transgenes in Drosophila. Hox genes encode DNA binding proteins that act as molecular switches for transcription, turning on the expression of groups of downstream target genes during embryogenesis. Hox proteins select these target genes in the genome by interacting with specific protein partners or cofactors. We are studying the regulation and function of the Hox gene fushi tarazu (ftz). We discovered that Ftz interacts with a novel cofactor – the orphan nuclear receptor Ftz-F1. Ftz and Ftz-F1 bind cooperatively to DNA to coordinately regulate target gene expression. Studies underway in the lab focus on: isolation of transcription factors that regulate ftz gene expression; analysis of how Ftz and Ftz-F1 interact to regulate transcription; bioinformatics approaches to identify downstream targets of the Ftz/Ftz-F1 protein complex; studies of novel mechanisms regulating Ftz-F1 nuclear receptor activity in the embryo; and investigation of how specific functions of Ftz and other Hox proteins have been acquired during the course of evolution of invertebrates and vertebrates. 

A second major project in the lab is to study how neuronal connections are established in the central nervous system during development. Normal function of the nervous system requires the formation of numerous precise connections between axons and their targets. How do axons find these targets? We have recently discovered that the Drosophila insulin receptor (DInR) functions as an axon guidance receptor in the developing visual system. DInR directs the formation of precise neuronal connections between the retina and brain, resulting in a highly ordered retinotopic map that allows the animal to decode visual input from the environment to “make sense” of the world. DInR regulates axon guidance via direct physical interaction with the SH2/SH3 adapter protein Dock. Dock in turn signals through p21-activated kinase (Pak), to cause changes in actin cytoskeleton which promote axonal migration. Our findings suggest a general role for the insulin receptor family in regulating axon guidance throughout the animal kingdom. We are currently investigating the role of DInR in regulating axon targeting; studying the requirements for its interaction with Dock and other signaling partners; and initiating studies to identify the ligand(s) that regulate DInR activity in the central nervous system. In the long term, these studies will contribute to our understanding of mechanisms underlying neuronal insulin receptor control of eating behavior, learning and memory in both invertebrates and vertebrates.

Ioannidis, P., Lu, Y., Kumar^, N., Creasy, T., Daugherty^, S., Chibucos, M.C., Orvis^, J.,Shetty,A.,     Ott, S., Flowers, M., Sengamalay, N., Tallon, L.J., Pick, L., Dunning Hotopp, J.C. (2014)  Rapid transcriptome sequencing of an invasive pest, the brown marmorated stink bug  Halyomorpha halys, BMC Genomics, 15:738  doi:10.1186/1471-2164-15-738.

Li, C.R., Guo, D. and Pick, L.  (2014) Independent signaling by Drosophila insulin receptor for axon guidance and growth. Front Physiol.,4:385. doi: 10.3389/fphys.2013.00385

Heffer^, A., Mahaffey, J., Grubbs, N. and Pick, L. (2013) The evolving role of the orphan nuclear receptor ftz-f1, a pair-rule segmentation gene.Evolution & Development, in press.

Crivat, G., Lizunov, V.A., Li, C. R., Stenkula, K.G., Zimmerberg, J., Cushmam, S.W.,and Pick, L.  (2013) Insulin stimulates translocation of human GLUT4 to the membrane in fat bodies of transgenic Drosophila melanogaster.PLoS One 10.1371/journal.pone.0077953 (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0077953)

Heffer, A., Xiang, J. and Pick, L.  (2013) Variation and constraint in Hox gene evolution. Proc. Natl. Acad. Sci.,110:2211-2216. doi10.1073/pnas.1210847110.

Lu, Y., Anderson, W.R., Zhang, H., Feng, S., and Pick, L. (2013) Functionalconservation of Drosophila FTZ-F1 and its mammalian homologs suggestsligand-independent regulation of NR5A family transcriptional activity.

Pick, L. and Heffer, A. (2012) Hox gene evolution: multiple mechanisms contributing to evolutionary novelties. Annal N.Y. Acad. Sci., Issue, This Year in Evolutionary Biology. doi: 10.1111/j.1749-6632.2011.06385.x

Heffer, A., Löhr, U. and Pick, L.(2011) ftz evolution: findings, hypotheses and speculations Bioessays 33:910-8. doi:10.1002/bies.201100112 (Back cover photo)

Heffer, A. and Pick, L.  (2011) Rapid isolation of gene homologs across taxa: Efficient identification and isolation of gene orthologs from non-model organism genomes, a technical report.  Evodevo. 2:7. [Article]

Heffer, A., Shultz, J. and Pick, L.4 (2010) Surprising flexibility in a conserved transcription factor over 550 million years of evolution. Proc. Natl. Acad. Sci. 107: 18040-18045. [Article]

Junell, A., Uvell, H., Davis, M.M., Edlundh-Rose, E., Antonsson, A., Pick, L.8, Engström, Y. (2010) The POU transcription factor Drifter/Ventral veinless regulates expression of Drosophila immune defense genes. Molecular & Cellular Biology 14:3672-84. [Article]

Zhang, H., Liu, J., Li, C.R., Momen, B., Kohanski, R.A. and Pick, L.4 (2009) Deletion of Drosophila Insulin-Like peptides causes growth defects and metabolic abnormalities. Proc. Natl. Acad. Sci. USA. 106:19617-19622

Hou, H.Y., Heffer, A., Anderson, W.R., Liu, J., Bowler, T. and Pick, L. (2009) Stripy Ftz target genes are coordinately regulated by Ftz-F1. Developmental Biology 335: 442-53.

Junell, A., Uvell, H. Pick, L. and Engstrm, Y. (2007) Isolation of regulators of Drosophila immune defense genes by a double interaction screen in yeast, Insect Biochemistry and Molecular Biology

Bowler, T. , Kosman, D., Licht, J. and Pick, L. (2006). A computational screen to identify genomic targets of the Ftz/Ftz-F1 homeodomain/nuclear receptor heterodimer. in press, Developmental Biology

Pick, L. Shultz, J., Anderson, W.R. and Woodard, C. (2006) The Ftz-F1 family: orphan nuclear receptors regulated by novel protein-protein interactions. In press for "Nuclear Receptors in Development" R. Taneja, editor

Oishi,K., Gaengel,K., Kamiya,K., Kim, I-K., Ying, H., Weber, U., Perkins,L., Tartaglia, M., Mlodzik, M., Pick, L. and Gelb, B.D. (2006) Transgenic Drosophila models of Noonan sydrome-causing RTPN11 gain-of-function mutations.Human Mol. Genet.15: 543-553.

Lohr, U. and Pick, L. (2005). Cofactor interaction motifs and the cooption of a homeotic Hox protein into the segmentation pathway of Drosophila melanogaster. Current Biology (Cell Press), 15: 643-649.

Song, J., Wu, L., Chen, Z., Kohanski, R.A. and Pick, L. (2003) Axons guided by Insulin Receptor in the Drosophila Visual System. Science 300: 502 - 505. Additional online Supplementary Material.

Lohr, U., Yussa, M. and Pick, L. (2001) Drosophila fushi tarazu: a gene on the border of homeotic function. Current Biology (Cell Press), 11:1 403-1412.

Yussa, M., Lohr, U., Su, K. and Pick, L. (2001). The nuclear receptor Ftz-F1 and homeodomain protein Ftz interact through evolutionarily conserved protein domains. Mechanisms of Development 107: 39-52.

Pick, L., Lohr, U. and Yu, Y. (2000). A Double Interaction Screen to isolate DNA binding and protein tethered transcription factors. In "Yeast Hybrid Techniques - genetic assay system for protein interactions." Ed. L. Zhu and G.J. Hannon. Eaton Publishing, Natick, MA.

Yu, Y., Yussa, M., Song, J., Hirsch, J. and Pick, L. (1999). A Double Interaction Screen identifies positive and negative ftz gene regulators and Ftz-interacting protein. Mechanisms of Development 83: 95-105.

Zhao, J. J., Vanario-Alonso, C.E. and Pick, L. (1999). Targeted ribozymes to study gene function in Drosophila. In "Intracellular Ribozyme Applications: Principles and Protocols" Ed. J. J. Rossi and L. Couture. Horizon Scientific Press, Norfolk, England.

Pick, L. And Lawrence, P.A. (1998). How does the fushi tarazu gene activate engrailed in the Drosophila embryo? Developmental Genetics 23:28-34.

Pick, L. (1998). Segmentation: painting stripes from flies to vertebrates. Developmental Genetics 23:1-10.

Han, W., Yu, Y., Kohanski, R.A. and Pick, L. (1998). An essential site in the ftz proximal enhancer interacts with multiple transcriptional activators. Mol. Cell. Biol.18: 3384-3394.

Yu, Y., Li, W., Su, K., Yussa, M., Han, W., Perrimon, N. and Pick, L. (1997) The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Fushi Tarazu. Nature 358: 552-555.

Zhao, J.J., Lazzarini, R.A. and Pick, L. (1996). Functional dissection of the mouse HoxA5 gene. EMBO Journal 15: 1313-1322.

Vanario-Alonso, C.E., OHara, E., McGinnis, W. and Pick, L. (1995). Targeted ribozymes reveal a conserved function of the Drosophila paired gene in sensory organ development. Mechanisms of Development 53: 323-328.

Jost, W., Yu, Y., Pick, L., Preiss, A. and Maier, D. (1995). Structure and regulation of the fushi tarazu gene from Drosophila hydei. Rouxs Archives of Developmental Biology 205: 160-170.

Yu, Y. and Pick, L. (1995). Non-periodic cues generate seven ftz stripes in the Drosophila embryo. Mechanisms of Development 50: 163-175.

• Gutjahr, T. Alonso, C. Pick, L. and Noll, M. (1994). Multiple regulatory elements direct the complex expression pattern of the Drosophila segmentation gene paired. Mechanisms of Development 48: 119-128.
• Zhao, J. and Pick, L. (1993). Generating loss-of-function phenotypes of the fushi tarazu gene with a targeted ribozyme in Drosophila. Nature 365:448-451.
• Han, W., Yu, Y., Altan, N. and Pick, L. (1993) Multiple proteins interact with the fushi tarazu proximal enhancer. Mol. Cell. Biol. 13: 5549-5559.
• Zhao, J., Lazzarini, R.A. and Pick, L. (1993). The mouse Hox 1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene. Genes & Development 7: 343-354.
• Furukubo-Tokunaga, K., Muller, M., Affolter, M., Pick, L., Kloter, U. and Gehring, W.J. (1992). In vivo Analysis of the Helix-Turn-Helix Motif of the fushi tarazu Homeodomain of Drosophila melanogaster. Genes & Development 6: 1082-1096.
• Amati, B., Pick, L., LaRoche,T. and Gasser, S. (1990) Nuclear scaffold attachment stimulates, but is not essential for ARS activity in Saccharomyces cerevisiae: analysis of the Drosophila ftz SAR. EMBO Journal 9, 4007-4016.
• Pick, L., Schier, A., Affolter, M., Schmidt-Glenewinkel, T. and Gehring, W.J. (1990) Analysis of the ftz upstream element: germ layer specific enhancers are independently autoregulated. Genes & Development 4: 1224 - 1239.

Awards & Professional Service

• 1980-1985NIH Predoctoral Trainee Fellowship
• 1985-1986Sandoz Foundation Postdoctoral Fellowship
• 1986-1989Damon Runyon-Walter Winchell Cancer Fund Postdoctoral Fellowship
• 1990-1993Alexandrine and Alexander L. Sinsheimer Fund, Junior Faculty Award
• 1992-1996Irma T. Hirschl Career Scientist Award
• 2001Center for Excellence in Youth Education, Mount Sinai School of Medicine in conjunction with the New York City Public Schools
• 2004 -2008      Director, Graduate Program in Molecular & Cell Biology (MOCB)
• 2012-2013, Program Director, Division of Integrated Organismal Sciences, National Science Foundation

Education

• 1977 B.A., Wesleyan University, Middletown, CT,
• 1986 Ph.D., Albert Einstein College of Medicine, Bronx, N.Y.
• 1986-1989 Postdoctoral Fellow, University of Basel, Switzerland.