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J. Peter Gergen, Ph.D.

gergenSUNY 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
Fax: 631-632-8575

  • Research Description

    fig 1Research 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.

    fig2Our 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 geneengrailed. 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.

    fig3A 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.

  • Publications


    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
  • Alumni
    Name Position in Gergen lab email location
    Martin Klingler Postdoctoral Associate
    Dean of Biology, University of Erlangen-Nurnberg
    Ben Aronson Postdoctoral Associate Professor, University of Redlands
    John Wheeler Postdoctoral Associate
    Principal Research Scientist, Janssen BioTherapeutics
    Kathy Wojtas Postdoctoral Associate VP and Medical Director, BGB Group
    Yasuno Iwasaki Postdoctoral Associate
    Postdoctoral Associate, Stony Brook University
    Joseph Duffy Doctoral student
    Head, Department of Biology & Biotechnology, WPI
    Chih-Cheng Tsai Doctoral student
    Associate Professor, Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School
    Melissaa Pepling Doctoral student
    Professor and Associate Chair, Department of Biology, Syracuse University
    Greg Golling Doctoral student Professor and Division Chair, Taft College
    Sunita Kramer Doctoral student
    Associate Professor and Associate Dean for Academic Affairs, Honors College, Rutgers University
    Linghui Li Doctoral student
    Associate Research Scientist, Academica Sinica, Taiwan
    Dan Tracey Doctoral student
    Associate Professor, Department of Biology, Indiana University Bloomington
    Christine VanderZwan Doctoral student Stay at home mother
    Pegine Walrad Doctoral student
    Anniversary Research Lecturer, Department of Biology, University of York
    Xiaoling Wang Doctoral student
    Research Associate, Laboratory of Biochemistry and Molecular Biology, Rockefeller University
    Lisa Prazak Doctoral student 
    Assistant Professor, Biology, Farmingdale State College
    Saiyu Hang Doctoral student
    Postdoctoral Associate, Harvard Medical School
    Kimberly Bell Doctoral student
    STEM Postdoctoral Associate, Center for Excellence in Learning & Teaching, Stony Brook
    Michael Higgins Doctoral student  
    Deborah Swantek Research Assistant
    Biology Teacher, Chantilly High School, Fairfax, VA
    Rammohan Ramakrishnan Masters student
    Quality Engineer, Medtronic, Minneapolis-St Paul
    Jinelle Wint Masters student PhD student, Stony Brook University
    Jennifer Shapp Masters student Current student
    Garfield Clunie, MD Undergraduate student
    Asst. Clinical Professor, Mount Sinai School of Medicine
    Howard Sussman, MD Undergraduate student
    Faculty, Family Medicine, Stony Brook University Hospital
    Odeniel Sertil, PhD Undergraduate student
    Forensic Scientist, Phoenix Police Department Crime Laboratory
    Christopher Magnifico, MD Undergraduate student Physician, Bayport, NY
    Michael Stebbins, PhD Undergraduate student
    VP of Science and Technology, Arnold Foundation
    Dayna Smith, MD Undergraduate student  
    Obstetrician-Gynecologist, Fayetteville, GA
    Susie Lin, MD Undergraduate Honors student
    Asst. Professor, Dept. of Oral and Maxillofacial Surgery, Vanderbilty University Medical Center
    Greg Banninger, PhD Undergraduate student 
    Patent Coordinator, University of Illinois Urbana-Champaign
    Mary Berketis-Simons Undergraduate student   Chemistry teacher, Seaford High School
    Sean Boykevisch, PhD Undergraduate student
    Asst. Director (Life Sciences) , Technology Licensing and Industry Relations, Stony Brook Reserch
    Genevieve Jospeh, PhD Undergraduate Honors student
    Admin. Asst., Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
    Steven Naymagon, MD Undergraduate student
    Asst. Professor, Internal Medicine, Icahn School of Medicine at Mount Sinai
    Michael Cressy, PhD Undergraduate student
    Science Research Teacher, Malverne High School
    Jocelin Abraham (Rimes) Undergraduate student Stay at home mother
    Sunita Singh (Celestrin) Undergraduate student Stay at home mother
    Kevin Celestrin, PhD Undergraduate student
    Postdoctoral Associate, Albert Einstein College of Medicine
    Giorgio Medranda, MD Undergraduate student
    Cardiovascular Disease Fellow, NYU Winthrop Hospital
    Conrad Tenenbaum, PhD Undergraduate Honors student
    Senior Associate, Blueprint Research Group, Princeton NJ
    Christopher Bianco Undergraduate student   PhD student, NYU School of Medicine
    Liujing Xing, PhD Undergraduate Honors student
    Scientific Analyst at Morrison & Forrester LLP, San Francisco, CA
    Seema Sawh Undergraduate student
    Account Manager, STEMCELL Technologies, New York, NY
    Angelita Tan Undergraduate student
    Doctoral Program in Nursing Practice, Columbia University
    Karthink Rao Undergraduate student
    Insurance Agent, Bankers Life, Westborough, MA
    Tianyu Zhan, PhD Undergraduate Honors student
    Senior Research Statistician, AbbVie Inc., Chicago, IL
    Haiyue Zhang Undergraduate Honors student
    Biostatistician, Massachusetts General Hospital Biostatistics Center, Boston, MA
    Mihai Andreca Undergraduate student
    Medical student Albert Einstein College of Medicine
    Emily Iocolano Undergraduate student
    Veterinary Assistant, The Animal Medical Center, New York, NY
    Kevin Skier Undergraduate Honors student  
    Medical student, University of Massachusetts