J. Peter Gergen, Ph.D.

gergen 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
Fax: 631-632-8575
E-mail: john.peter.gergen@stonybrook.edu

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 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.

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.
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
- Yasuno Iwasaki
  
  Postdoc2015-current
- Jennifer Shapp
  
  Master's Student2017-current

Alumni

Name	Position in Gergen lab	email	location

Martin Klingler	Postdoctoral Associate	martin.klingler@fau.de	Dean of Biology, University of Erlangen-Nurnberg
Ben Aronson	Postdoctoral Associate	Ben_Aronson@redlands.edu	Professor, University of Redlands
John Wheeler	Postdoctoral Associate	john_wheeler@sbcglobal.net	Principal Research Scientist, Janssen BioTherapeutics
Kathy Wojtas	Postdoctoral Associate	kathy.wojtas@gmail.com	VP and Medical Director, BGB Group
Yasuno Iwasaki	Postdoctoral Associate	yasuno.iwasaki@stonybrook.edu	Postdoctoral Associate, Stony Brook University

Joseph Duffy	Doctoral student	jduffy@wpi.edu	Head, Department of Biology & Biotechnology, WPI
Chih-Cheng Tsai	Doctoral student	tsaich@rwjms.rutgers.edu	Associate Professor, Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School
Melissaa Pepling	Doctoral student	mepeplin@syr.edu	Professor and Associate Chair, Department of Biology, Syracuse University
Greg Golling	Doctoral student	ggolling@taftcollege.edu	Professor and Division Chair, Taft College
Sunita Kramer	Doctoral student	sunita.kramer@rutgers.edu	Associate Professor and Associate Dean for Academic Affairs, Honors College, Rutgers University
Linghui Li	Doctoral student	lli@ibms.sinica.edu.tw	Associate Research Scientist, Academica Sinica, Taiwan
Dan Tracey	Doctoral student	dtracey@indiana.edu	Associate Professor, Department of Biology, Indiana University Bloomington
Christine VanderZwan	Doctoral student	christine.butler@gmail.com	Stay at home mother
Pegine Walrad	Doctoral student	pegine.walrad@york.ac.uk	Anniversary Research Lecturer, Department of Biology, University of York
Xiaoling Wang	Doctoral student	xiaoling.wang@rockefeller.edu	Research Associate, Laboratory of Biochemistry and Molecular Biology, Rockefeller University
Lisa Prazak	Doctoral student	prazakl@farmingdale.edu	Assistant Professor, Biology, Farmingdale State College
Saiyu Hang	Doctoral student	saiyu_hang@hms.harvard.edu	Postdoctoral Associate, Harvard Medical School
Kimberly Bell	Doctoral student	kimberly.bell@stonybrook.edu	STEM Postdoctoral Associate, Center for Excellence in Learning & Teaching, Stony Brook
Michael Higgins	Doctoral student	miluis.higgins@gmail.com

Deborah Swantek	Research Assistant	swantekd@gmail.com	Biology Teacher, Chantilly High School, Fairfax, VA

Rammohan Ramakrishnan	Masters student	r_krishna90@yahoo.com	Quality Engineer, Medtronic, Minneapolis-St Paul
Jinelle Wint	Masters student	jinelle.wint@stonybrook.edu	PhD student, Stony Brook University
Jennifer Shapp	Masters student	jennifer.shapp@stonybrook.edu	Current student

Garfield Clunie, MD	Undergraduate student	garfield.clunie@mssm.edu	Asst. Clinical Professor, Mount Sinai School of Medicine
Howard Sussman, MD	Undergraduate student	howard.sussman@stonybrookmedicine.edu	Faculty, Family Medicine, Stony Brook University Hospital
Odeniel Sertil, PhD	Undergraduate student	osertil@gmail.com	Forensic Scientist, Phoenix Police Department Crime Laboratory
Christopher Magnifico, MD	Undergraduate student	cmagnifi@sgu.edu	Physician, Bayport, NY
Michael Stebbins, PhD	Undergraduate student	Michael.j.stebbins@gmail.com	VP of Science and Technology, Arnold Foundation
Dayna Smith, MD	Undergraduate student		Obstetrician-Gynecologist, Fayetteville, GA
Susie Lin, MD	Undergraduate Honors student	susie.lin@vanderbilt.edu	Asst. Professor, Dept. of Oral and Maxillofacial Surgery, Vanderbilty University Medical Center
Greg Banninger, PhD	Undergraduate student	gbanning@illinois.edu	Patent Coordinator, University of Illinois Urbana-Champaign
Mary Berketis-Simons	Undergraduate student		Chemistry teacher, Seaford High School
Sean Boykevisch, PhD	Undergraduate student	sean.boykevisch@stonybrook.edu	Asst. Director (Life Sciences) , Technology Licensing and Industry Relations, Stony Brook Reserch
Genevieve Jospeh, PhD	Undergraduate Honors student	genevieve.joseph@mssm.edu	Admin. Asst., Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Steven Naymagon, MD	Undergraduate student	steven.naymagon@mountsinai.org	Asst. Professor, Internal Medicine, Icahn School of Medicine at Mount Sinai
Michael Cressy, PhD	Undergraduate student	mcressy@malverne.k12.ny.us	Science Research Teacher, Malverne High School
Jocelin Abraham (Rimes)	Undergraduate student	jocelin.rimes@gmail.com	Stay at home mother
Sunita Singh (Celestrin)	Undergraduate student	Thecelestrins@gmail.com	Stay at home mother
Kevin Celestrin, PhD	Undergraduate student	kevin.celestrin@gmail.com	Postdoctoral Associate, Albert Einstein College of Medicine
Giorgio Medranda, MD	Undergraduate student	gionyc86@gmail.com	Cardiovascular Disease Fellow, NYU Winthrop Hospital
Conrad Tenenbaum, PhD	Undergraduate Honors student	conrad.tenenbaum@gmail.com	Senior Associate, Blueprint Research Group, Princeton NJ
Christopher Bianco	Undergraduate student		PhD student, NYU School of Medicine
Liujing Xing, PhD	Undergraduate Honors student	xingliujing@gmail.com	Scientific Analyst at Morrison & Forrester LLP, San Francisco, CA
Seema Sawh	Undergraduate student	seema.sawh@stemcell.com	Account Manager, STEMCELL Technologies, New York, NY
Angelita Tan	Undergraduate student	angelitatan1@gmail.com	Doctoral Program in Nursing Practice, Columbia University
Karthink Rao	Undergraduate student	meleegc@yahoo.com	Insurance Agent, Bankers Life, Westborough, MA
Tianyu Zhan, PhD	Undergraduate Honors student	sewen67@gmail.com	Senior Research Statistician, AbbVie Inc., Chicago, IL
Haiyue Zhang	Undergraduate Honors student	haiyuezhang222@gmail.com	Biostatistician, Massachusetts General Hospital Biostatistics Center, Boston, MA
Mihai Andreca	Undergraduate student	mihai.andreca@yahoo.com	Medical student Albert Einstein College of Medicine
Emily Iocolano	Undergraduate student	emily.iocolano6@gmail.com	Veterinary Assistant, The Animal Medical Center, New York, NY
Kevin Skier	Undergraduate Honors student		Medical student, University of Massachusetts