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J. Peter Gergen, Ph.D.
SUNY Distinguished Service Professor
Department of Biochemistry and Cell Biology
Center for Developmental Genetics CMM/BLL 112
Stony Brook University
Stony Brook, NY 11794-5140
Office telephone: 631-632-1190
Lab telephone: 631-632-9031
- Research Description
Research in the Gergen laboratory uses the developmental genetic framework of the Drosophila embryo to investigate the regulation of gene expression, with a primary focus on the Runt transcription factor. Runt is the founding member of the Runx family of transcriptional regulators. Runx proteins are present in all animal species examined, but not in plant or microbial eukaryotic systems. Runt is best characterized for its role in the Drosophila embryo where it has vital roles in several pathways, including sex determination, segmentation, and neurogenesis . Mutations in all three human Runx genes are associated with genetic disease, and targeted mutagenesis experiments in the mouse indicate that these genes have vital roles in several pathways, including hematopoeisis, neurogenesis and osteogenesis A unifying aspect of Runx function in these many different pathways is a role in cell fate specification. An intriguing aspect of regulation by Runt and the vertebrate Runx proteins is that they function both as transcriptional activators and repressors, depending both on the specific target gene and the developmental context. Indeed, this context-dependence is central to the Runt-dependent regulation of the segment-polarity genes during segmentation.
Our recent work has taken advantage of the differential sensitivity of different segment-polarity gene targets to quantitative manipulations in Runt activity. Runt is a potent repressor of the segment-polarity gene engrailed. We conducted a genetic screen to identify factors that contribute to this Runt-dependent repression. Further characterization of the factors identified in this screen revealed two distinct steps in en repression: 1) an establishment phase that involves a DNA-binding protein encoded by the tramtrack gene, and 2) a maintenance phase that involves the co-repressor Groucho and the Rpd3 histone de-acetylase. In vivo structure-function studies on Runt confirmed the functional distinction between establishment and maintenance and further revealed the surprising result that DNA-binding defective forms of Runt retain the ability to regulate a subset of gene targets. This genetic screen identified other factors that contribute to Runt’s potency, and ongoing work aims to further elucidate the roles of these factors in Runt-dependent regulation.
A second major project takes advantage of several attributes of the segment-polarity target gene sloppy-paired1 ( slp1). One key advantage is the simple combinatorial rules that are responsible for modulating Runt’s activity as both an activator and a repressor of slp1expression. Indeed, using straightforward genetic manipulations it is possible to achieve uniform, physiologically relevant Runt-dependent activation or repression of slp1 in all somatic cells of a late blastoderm stage embryo. These embryos provide a platform for biochemical studies on the in vivoprotein-DNA interactions associated with slp1 repression. The results indicate that the initial establishment of repression does not involve changes in chromatin re-modeling or modification, nor the assembly of an initiation complex at the slp1 promoter, but is due instead to developmentally regulated transcriptional elongation. Ongoing studies are aimed at identifying the specific transcriptional step that is sensitive to regulation and characterizing the functional contributions of the factor(s) that are involved. This work is complemented by studies on the slp1 cis-regulatory region that investigate the quantitative contributions of different cis-regulatory DNA elements to developmentally regulated transcriptional elongation.
Mendoza-García, P., Hugosson, F., Fallah, M., Higgins, M.L., Iwasaki, Y., Pfeifer, K., Wolfstetter, G., Varshney, G., Popichenko, D., Gergen, J.P., Hens, K., Deplancke, B. and Palmer, R.H. (2017) The Zic family homolog Odd-paired regulates Alk expression in Drosophila, PLoS Genetics, 13:e1006617. PMID: 28369060. Abstract
Hang, S. and Gergen, J.P. (2017) Different modes of enhancer-specific regulation by Runt and Eve-skipped during Drosophila segmentation. Mol Biol Cell, Epub Jan 11 , PMID:28077616. Abstract
Walrad PB, Hang S, Gergen JP. (2011) Hairless is a cofactor for Runt-dependent transcriptional regulation. Mol Biol Cell. 22(8):1364-74. doi: 10.1091/mbc.E10-06-0483. Abstract
Wang X, Hang S, Prazak L, Gergen JP. (2010) NELF potentiates gene transcription in the Drosophila embryo. PLoS One 5(7):e11498. doi: 10.1371/journal.pone.0011498. Abstract
Funakoshi Y, Negishi Y, Gergen JP, Seino J, Ishii K, Lennarz WJ, Matsuo I, Ito Y, Taniguchi N, Suzuki T. (2010) Evidence for an essential deglycosylation-independent activity of PNGase in Drosophila melanogaster PLoS One 5(5):e10545. doi: 10.1371/journal.pone.0010545. Abstract
Walrad PB, Hang S, Joseph GS, Salas J, Gergen JP. (2010) Distinct contributions of conserved modules to Runt transcription factor activity. Mol Biol Cell. 21(13):2315-26. doi: 10.1091/mbc.E09-11-0953. Epub 2010 May 12. Abstract
Prazak L, Fujioka M, Gergen JP (2010) Non-additive interactions involving two distinct elements mediate sloppy-paired regulation by pair-rule transcription factors. Dev Biol. 344(2):1048-59. doi: 10.1016/j.ydbio.2010.04.026. Epub 2010 May 6. Abstract
Wang, X., Lee, C., Gilmour, D.S. and Gergen, J.P. (2007) Transcription elongation controls cell specification in the Drosophila embryo, Genes & Dev., 21:1031-6. Abstract
VanderZwan-Butler, C.J., Prazak, L.M. and Gergen, J.P. (2006) The HMG-box protein Lilli is required for Runt-dependent activation of the pair-rule gene fushi tarazu, Developmental Biology, 301:350-360. Abstract
LaLonde, M., Janssens, H., Yun, S., Crosby, J., Redina, O., Olive, V., Altshuller, Y., Du, G., Gergen, J.P. and Frohman, M.A. (2006) A role for Phospholipase D in Drosophila embryonic cellularization, BMC Developmental Biology, 6:60.
Gilbert, M.M., Weaver, B.K., Gergen, J.P. and Reich, N.C. (2005) A novel functional activator of the Drosophila JAK/STAT pathway, Unpaired2, is revealed by an in vivo reporter of pathway activation, Mech Dev. 122:939-48.
LaLonde, M.M., Janssens, H., Rosenbaum, E., Choi, S.-Y., Gergen, J.P., Colley, N.J., Stark, W.S. and Frohman, M.A. (2005) Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid. J. Cell Biol., 169:471-9.
Van Wijnen, A.J., Stein, G.S., Gergen, J.P., Groner, Y., Hiebert, S.W., Ito, Y., Liu, P., Neil, J.C., Ohki, M. and Speck, N. (2004) Nomenclature for Runt-related (RUNX) proteins. Oncogene 23:4209-10.
Swantek, D. and Gergen, J.P. (2004) Ftz modulates Runt's activity as an activator or repressor of segment-polarity gene transcription, Development 131:2281-90. Abstract
VanderZwan, C., Wheeler, J.C., Li, L.-H., Tracey, W.D., and Gergen, J.P. (2003) A DNA binding-independent pathway of repression by the Drosophila Runt protein. Blood Cells Mol. Dis., 30:207-222. Abstract
Wheeler, John C., Vander Zwan, C., Xu, X., Swantek, D., Tracey, W. D. and Gergen, J.P. (2002) Distinct in vivo requirements for establishment versus maintenance of transcriptional repression, Nature Genetics, 32:206-210. Abstract
Rudolph, M.J. and Gergen, J.P. (2001) DNA-binding by Ig-fold proteins, Nature Structural Biology, 8:384-386
Wheeler, J.C., Shigesada, K, Gergen, J. P. and Ito, Y. (2000) Mechanismsof transcriptional regulation by Runt domain proteins, Seminars in Cell and Developmental Biology, 11:369-375.
Gergen, J.P. (2000) Transcriptional regulation by Runt domain proteins in development and disease, Editorial Perspective (Guest Editor of this review volume), Seminars in Cell and Developmental Biology, 11:325-326.
Tracey, W.D., Ning, X., Klingler, M., Kramer, S.G. and Gergen, J.P. (2000) Quantitative analysis of gene function in the Drosophila embryo, Genetics 154:273-284. Abstract
Li, L.-H. and Gergen, J.P. (1999) Differential interactions between Brother proteins and Runt domain proteins in the Drosophila embryo and eye, Development, 126:3313-3322. Abstract
Wolff, C., Pepling, M., Gergen, P. and Klingler, M. (1999) Structure and evolution of a pair-rule interaction element: runt regulatory sequences in D. melanogaster and D. virilis. Mech. Dev, 80:87-99.
Kramer, S.G., Jinks, T.M., Schedl, P. and Gergen, J.P. (1999) Direct activation of Sex-lethal transcription by the Drosophila Runt protein. Development 126:191-200. Abstract
Tsai, C-C., Kramer, S.G. and Gergen, J.P. (1998) Pair-rule gene runt restricts orthodenticle expression to the presumptive head of the Drosophila embryo. Developmental Genetics 23:35-44. Abstract
Tracey, W.D., Pepling, M.E., Horb, M., Thomsen, G.T. and Gergen, J.P. (1998) A Xenopus homologue of Aml-1 reveals unexpected patterning mechanisms leading to the formation of embryonic blood. Development 125:1371-1380. Abstract
Chen, B., Chu, T., Harms, E., Gergen, J.P. and Strickland, S. (1998) Mapping of Drosophila mutations using site-specific male recombination. Genetics 149:157-163.
Aronson, B.D., Fisher, A.L., Blechman, K., Caudy, M. and Gergen, J.P. (1997) Groucho dependent and independent repression activities of Runt domain proteins. Mol. Cell Biol., 17:5581-5587. Abstract
Klingler, M., Soong, J., Butler, B. and Gergen, J.P. (1996) Disperse versus compact elements for the regulation of runt stripes in Drosophila. Develop. Biol., 177:73-84. Abstract
Lieberfarb, M.E., Chu, T., Wreden, C., Theurkauf, W., Gergen, J.P. and Strickland, S. (1996) Mutations that perturb poly(A)-dependent maternal mRNA activation block the initiation of development. Development, 122:579-588.
Golling, G., Li, L.-H., Pepling, M.E., Stebbins, M. and Gergen, J.P. (1996) Drosophila homologues of proto-oncogene product PEBP2/CBF b regulate the DNA-binding properties of Runt. Mol. Cell Biol., 16:932-942. Abstract
Duffy, J. B., Wells, J. and Gergen, J.P. (1996) Dosage-sensitive maternal modifiers of the segmentation gene runt. Genetics, 142:839-852. Abstract
Pepling, M.E. and Gergen, J.P. (1995) Conservation and function of the transcriptional regulatory protein Runt. Proc. Nat'l. Acad. Sci., USA, 92:9087-9091. Abstract
Tsai, C. and Gergen, J.P. (1995) Pair--rule expression of the Drosophila fushi tarazu gene: a nuclear receptor response element mediates the opposing regulatory effects of runt and hairy. Development, 121:453-462.
Sallés, F.J., Leiberfarb, M.E., Wreden, C., Gergen, J.P. and Strickland, S. (1994) Coordinate initiation of Drosophila development by regulated polyadenylation of maternal mRNAs. Science, 266:1996-1999.
Tsai, C. and Gergen, J.P. (1994) Gap gene properties of the pair-rule gene runt during Drosophila segmentation. Development, 120:1671-1683. Abstract
Duffy, J. B. and Gergen, J.P. (1994) Sex, segments and the CNS: Common mechanisms of cell fate determination. In Advances in Genetics, Vol. 31 (J. Dunlap and J. Hall, eds.), New York, Academic Press, pp. 1-28.
Kagoshima, H., Shigesada, K., Satake, M., Ito, Y., Miyoshi, H., Ohki, M., Pepling, M. and Gergen, J.P. (1993) The Runt-domain identifies a new family of heteromeric transcriptional regulators. Trends in Genetics 9:338-341.
Klingler, M. and Gergen, J.P. (1993) Regulation of runt transcription by Drosophila segmentation genes. Mech. Dev. 43:3-19. Abstract
Butler, B.A., Soong, J. and Gergen, J.P. (1992) The Drosophila segmentation gene runt has an extended cis-regulatory region that is required for vital expression at other stages of development. Mech. Dev. 39:17-28. Abstract
Duffy, J.B. and Gergen, J.P. (1991) The Drosophila segmentation gene runt acts as a position-specific numerator element necessary for the uniform expression of the sex-determining gene Sex-lethal. Genes & Develop. 5:2176 - 2187. Abstract
Duffy, J. B., Kania, M.A., and Gergen, J.P. (1991) Expression and function of the Drosophila gene runt in early stages of neural development. Development 113:1223-1230. Abstract
Kania, M.A., Bonner, A.S., Duffy, J. and Gergen, J.P. (1990) The segmentation gene runt encodes a novel nuclear protein that is also expressed in the developing nervous system. Genes & Develop. 4:1701 - 1713. Abstract
Butler, B.A., Appeddu, P. and Gergen, J.P. (1989). Region-specific mutations of the Drosophila segmentation gene runt. In: Developmental Biology, UCLA Symposia on Molecular and Cellular Biology, New Series, Vol. 125. (E. Davidson, J. Ruderman and J. Posakony, eds.). Alan R. Liss, Inc., New York, New York. pp 105 - 112.
Ingham, P.W. and Gergen, J.P. (1988). Interactions between the pair-rule genes runt, hairy, even-skipped and fushi tarazu generate a molecular prepattern in the Drosophila embryo. (Suppl., Mechanisms of Segmentation) Development 104:51-60.
Gergen, J.P. and Butler, B.A. (1988). Isolation of the Drosophila segmentation gene runt and analysis of its expression during embryogenesis. Genes & Develop. 2:1179-1193. Abstract
Gergen, J.P. (1987). Drosophila segmentation genes and blastoderm cell identities. Bioessays 6:61-66.
Gergen, J.P. (1987). Dosage compensation in Drosophila: Evidence that daughterless and Sex-lethal control X-chromosome activity at the blastoderm stage of embryogenesis. Genetics 117:477-485. Abstract
Tully, T. and Gergen, J.P. (1986). Deletion mapping of the Drosophila memory mutant amnesiac. J. Neurogenetics 3:33-47.
Gergen, J.P., Coulter, D. and Wieschaus, E. (1986). Segmental pattern and blastoderm cell identities. In Gametogenesis and the Early Embryo, (J. Gall, ed.) pp. 195-220. New York: Alan R. Liss.
Gergen, J.P. and Wieschaus, E.F. (1986). Localized requirements for gene activity in segmentation of Drosophila embryos: Analysis of armadillo, fused, giant and unpairedmutations in mosaic embryos. Wilhelm Roux's Arch. 195:49-62.
Gergen, J.P. and Wieschaus, E.F. (1986). Dosage requirements for runt in the segmentation of Drosophila embryos. Cell 45:289-299. Abstract
Zusman, S., Coulter, D. and Gergen, J.P. (1985). Lethal mutations induced in the proximal X-chromosome of Drosophila melanogaster using P-M hybrid dysgenesis. Dros. Inf. Serv. 61:217-218.
Gergen, J.P. and Wieschaus, E.F. (1985). The localized requirements for a gene affecting segmentation in Drosophila: Analysis of larvae mosaic for runt. Develop. Biol. 109:321-335. Abstract
Sharp, W., DeFranco, D., Silberklang, M., Hosbach, H.A., Schmidt, T., Kubli, E., Gergen, J.P., Wensink, P.C. and Soll, D. (1981). The initiator tRNA genes of Drosophila melanogaster: Evidence for a tRNA pseudogene. Nucleic Acids Research, 9:5867-5882.
Gergen, J.P., Loewenberg, J.Y. and Wensink, P.C. (1981). tRNA 2 lys gene clusters in Drosophila. J. Mol. Biol., 147:475-499.
Barnett, T., Pachl, C., Gergen, J.P. and Wensink, P.C. (1980). The isolation and characterization of Drosophila yolk protein genes. Cell 21:729-738.
Gergen, J.P., Stern, R.H. and Wensink, P.C. (1979). Filter replicas and permanent collections of recombinant DNA plasmids. Nucleic Acids Research 7:2115-2136 (1979). Abstract
- Lab Members
Name Position in Gergen lab location Martin Klingler Postdoctoral Associate email@example.comDean of Biology, University of Erlangen-Nurnberg Ben Aronson Postdoctoral Associate Ben_Aronson@redlands.edu Professor, University of Redlands John Wheeler Postdoctoral Associate firstname.lastname@example.orgPrincipal Research Scientist, Janssen BioTherapeutics Kathy Wojtas Postdoctoral Associate email@example.com VP and Medical Director, BGB Group Yasuno Iwasaki Postdoctoral Associate firstname.lastname@example.orgPostdoctoral Associate, Stony Brook University Joseph Duffy Doctoral student email@example.comHead, Department of Biology & Biotechnology, WPI Chih-Cheng Tsai Doctoral student firstname.lastname@example.orgAssociate Professor, Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School Melissaa Pepling Doctoral student email@example.comProfessor and Associate Chair, Department of Biology, Syracuse University Greg Golling Doctoral student firstname.lastname@example.org Professor and Division Chair, Taft College Sunita Kramer Doctoral student email@example.comAssociate Professor and Associate Dean for Academic Affairs, Honors College, Rutgers University Linghui Li Doctoral student firstname.lastname@example.orgAssociate Research Scientist, Academica Sinica, Taiwan Dan Tracey Doctoral student email@example.comAssociate Professor, Department of Biology, Indiana University Bloomington Christine VanderZwan Doctoral student firstname.lastname@example.org Stay at home mother Pegine Walrad Doctoral student email@example.comAnniversary Research Lecturer, Department of Biology, University of York Xiaoling Wang Doctoral student firstname.lastname@example.orgResearch Associate, Laboratory of Biochemistry and Molecular Biology, Rockefeller University Lisa Prazak Doctoral student email@example.comAssistant Professor, Biology, Farmingdale State College Saiyu Hang Doctoral student firstname.lastname@example.orgPostdoctoral Associate, Harvard Medical School Kimberly Bell Doctoral student email@example.comSTEM Postdoctoral Associate, Center for Excellence in Learning & Teaching, Stony Brook Michael Higgins Doctoral student firstname.lastname@example.org Deborah Swantek Research Assistant email@example.comBiology Teacher, Chantilly High School, Fairfax, VA Rammohan Ramakrishnan Masters student firstname.lastname@example.orgQuality Engineer, Medtronic, Minneapolis-St Paul Jinelle Wint Masters student email@example.com PhD student, Stony Brook University Jennifer Shapp Masters student firstname.lastname@example.org Current student Garfield Clunie, MD Undergraduate student email@example.comAsst. Clinical Professor, Mount Sinai School of Medicine Howard Sussman, MD Undergraduate studentFaculty, Family Medicine, Stony Brook University Hospital Odeniel Sertil, PhD Undergraduate student firstname.lastname@example.orgForensic Scientist, Phoenix Police Department Crime Laboratory Christopher Magnifico, MD Undergraduate student email@example.com Physician, Bayport, NY Michael Stebbins, PhD Undergraduate student Michael.firstname.lastname@example.orgVP of Science and Technology, Arnold Foundation Dayna Smith, MD Undergraduate studentObstetrician-Gynecologist, Fayetteville, GA Susie Lin, MD Undergraduate Honors student email@example.comAsst. Professor, Dept. of Oral and Maxillofacial Surgery, Vanderbilty University Medical Center Greg Banninger, PhD Undergraduate student firstname.lastname@example.orgPatent Coordinator, University of Illinois Urbana-Champaign Mary Berketis-Simons Undergraduate student Chemistry teacher, Seaford High School Sean Boykevisch, PhD Undergraduate student email@example.comAsst. Director (Life Sciences) , Technology Licensing and Industry Relations, Stony Brook Reserch Genevieve Jospeh, PhD Undergraduate Honors student firstname.lastname@example.orgAdmin. Asst., Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai Steven Naymagon, MD Undergraduate student email@example.comAsst. Professor, Internal Medicine, Icahn School of Medicine at Mount Sinai Michael Cressy, PhD Undergraduate student firstname.lastname@example.orgScience Research Teacher, Malverne High School Jocelin Abraham (Rimes) Undergraduate student email@example.com Stay at home mother Sunita Singh (Celestrin) Undergraduate student Thecelestrins@gmail.com Stay at home mother Kevin Celestrin, PhD Undergraduate student firstname.lastname@example.orgPostdoctoral Associate, Albert Einstein College of Medicine Giorgio Medranda, MD Undergraduate student email@example.comCardiovascular Disease Fellow, NYU Winthrop Hospital Conrad Tenenbaum, PhD Undergraduate Honors student firstname.lastname@example.orgSenior Associate, Blueprint Research Group, Princeton NJ Christopher Bianco Undergraduate student PhD student, NYU School of Medicine Liujing Xing, PhD Undergraduate Honors student email@example.comScientific Analyst at Morrison & Forrester LLP, San Francisco, CA Seema Sawh Undergraduate student firstname.lastname@example.orgAccount Manager, STEMCELL Technologies, New York, NY Angelita Tan Undergraduate student email@example.comDoctoral Program in Nursing Practice, Columbia University Karthink Rao Undergraduate student firstname.lastname@example.orgInsurance Agent, Bankers Life, Westborough, MA Tianyu Zhan, PhD Undergraduate Honors student email@example.comSenior Research Statistician, AbbVie Inc., Chicago, IL Haiyue Zhang Undergraduate Honors student firstname.lastname@example.orgBiostatistician, Massachusetts General Hospital Biostatistics Center, Boston, MA Mihai Andreca Undergraduate student email@example.comMedical student Albert Einstein College of Medicine Emily Iocolano Undergraduate student firstname.lastname@example.orgVeterinary Assistant, The Animal Medical Center, New York, NY Kevin Skier Undergraduate Honors studentMedical student, University of Massachusetts