Patrick O'Farrell, PhD
Professor
Biochemistry and Biophysics
School of Medicine

Having found that slowing early rapid cell cycles is due to prolongation of S phase, the period of DNA replication, we are studying this control. This prolongation of S phase is tightly integrated with a developmental program of chromatin changes that introduces epigenetic controls. Using GFP tagged proteins marking molecular hallmarks of these events, we are able to watch them occur in real time in embryos and to probe the processes that regulate their onset.

A newer effort explores the genetics and biology of the mitochondria. Our principle interest is in a newly recognized mystery. The mitochondrial genome encodes functions that benefit the host rather than propagation and transmission of the mitochondrial genome. This would not be problem if evolution of this genome were based on the usual selection for fit organisms as Darwin suggests. However, we found that selection is based on the ability of genomes to compete for transmission from one generation to the next. This ought to select for selfish genes promoting genome success. To achieve the real outcome, the host manipulates the competition to favor genes to its benefit. We are trying to understand how this managed evolution is achieved.

• Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila.
  Genes & development 2019 Seller CA, Cho CY, O'Farrell PH
• Rif1 prolongs the embryonic S phase at the Drosophila mid-blastula transition.
  PLoS biology 2018 Seller CA, O'Farrell PH
• Sophisticated lessons from simple organisms: appreciating the value of curiosity-driven research.
  Disease models & mechanisms 2017 Duronio RJ, O'Farrell PH, Sluder G, Su TT
• The Mitochondrial DNA Polymerase Promotes Elimination of Paternal Mitochondrial Genomes.
  Current biology : CB 2017 Yu Z, O'Farrell PH, Yakubovich N, DeLuca SZ
• Timing the Drosophila Mid-Blastula Transition: A Cell Cycle-Centered View.
  Trends in genetics : TIG 2016 Yuan K, Seller CA, Shermoen AW, O'Farrell PH
• Selfish drive can trump function when animal mitochondrial genomes compete.
  Nature genetics 2016 Ma H, O'Farrell PH
• TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos.
  Genes & development 2016 Yuan K, O'Farrell PH
• Growing an Embryo from a Single Cell: A Hurdle in Animal Life.
  Cold Spring Harbor perspectives in biology 2015 O'Farrell PH
• Selections that isolate recombinant mitochondrial genomes in animals.
  eLife 2015 Ma H, O'Farrell PH
• Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition.
  Current biology : CB 2015 Yuan K, O'Farrell PH
• From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition.
  Annual review of genetics 2014 Farrell JA, O'Farrell PH
• Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster.
  Nature genetics 2014 Ma H, Xu H, O'Farrell PH
• Two-dimensional gel electrophoresis and the beginning of proteomics.
  Clinical chemistry 2014 O'Farrell PH
• Illuminating DNA replication during Drosophila development using TALE-lights.
  Current biology : CB 2014 Yuan K, Shermoen AW, O'Farrell PH
• Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling.
  Current biology : CB 2013 Farrell JA, O'Farrell PH
• Different cyclin types collaborate to reverse the S-phase checkpoint and permit prompt mitosis.
  The Journal of cell biology 2012 Yuan K, Farrell JA, O'Farrell PH
• Embryonic onset of late replication requires Cdc25 down-regulation.
  Genes & development 2012 Farrell JA, Shermoen AW, Yuan K, O'Farrell PH
• Barriers to male transmission of mitochondrial DNA in sperm development.
  Developmental cell 2012 DeLuca SZ, O'Farrell PH
• Quiescence: early evolutionary origins and universality do not imply uniformity.
  Philosophical transactions of the Royal Society of London. Series B, Biological sciences 2011 O'Farrell PH
• Developmental control of late replication and S phase length.
  Current biology : CB 2010 Shermoen AW, McCleland ML, O'Farrell PH
• Nitric oxide synthase is not essential for Drosophila development.
  Current biology : CB 2010 Yakubovich N, Silva EA, O'Farrell PH
• Patrick H. O'Farrell.
  Current biology : CB 2010 O'Farrell PH
• DNA replication times the cell cycle and contributes to the mid-blastula transition in Drosophila embryos.
  The Journal of cell biology 2009 McCleland ML, Shermoen AW, O'Farrell PH
• Dissection of a hypoxia-induced, nitric oxide-mediated signaling cascade.
  Molecular biology of the cell 2009 Dijkers PF, O'Farrell PH
• Influence of cyclin type and dose on mitotic entry and progression in the early Drosophila embryo.
  The Journal of cell biology 2009 McCleland ML, Farrell JA, O'Farrell PH
• Phagocytosis of Candida albicans by RNAi-treated Drosophila S2 cells.
  Methods in molecular biology (Clifton, N.J.) 2009 Stroschein-Stevenson SL, Foley E, O'Farrell PH, Johnson AD
• The pre-omics era: the early days of two-dimensional gels.
  Proteomics 2008 O'Farrell PH
• Manipulating the metazoan mitochondrial genome with targeted restriction enzymes.
  Science (New York, N.Y.) 2008 Xu H, DeLuca SZ, O'Farrell PH
• An RNA interference screen identifies a novel regulator of target of rapamycin that mediates hypoxia suppression of translation in Drosophila S2 cells.
  Molecular biology of the cell 2008 Lee SJ, Feldman R, O'Farrell PH
• Anillin: a pivotal organizer of the cytokinetic machinery.
  Biochemical Society transactions 2008 Hickson GR, O'Farrell PH
• RNAi of mitotic cyclins in Drosophila uncouples the nuclear and centrosome cycle.
  Current biology : CB 2008 McCleland ML, O'Farrell PH
• Rho-dependent control of anillin behavior during cytokinesis.
  The Journal of cell biology 2008 Hickson GR, O'Farrell PH
• Drosophila calcineurin promotes induction of innate immune responses.
  Current biology : CB 2007 Dijkers PF, O'Farrell PH
• The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing.
  Nature cell biology 2006 Saleh MC, van Rij RP, Hekele A, Gillis A, Foley E, O'Farrell PH, Andino R
• Rho-kinase controls cell shape changes during cytokinesis.
  Current biology : CB 2006 Hickson GR, Echard A, O'Farrell PH
• Identification of Drosophila gene products required for phagocytosis of Candida albicans.
  PLoS biology 2005 Stroschein-Stevenson SL, Foley E, O'Farrell PH, Johnson AD
• Terminal cytokinesis events uncovered after an RNAi screen.
  Current biology : CB 2004 Echard A, Hickson GR, Foley E, O'Farrell PH
• Functional dissection of an innate immune response by a genome-wide RNAi screen.
  PLoS biology 2004 Foley E, O'Farrell PH
• Embryonic cleavage cycles: how is a mouse like a fly?
  Current biology : CB 2004 O'Farrell PH, Stumpff J, Su TT
• Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of DNA replication in Drosophila.
  BMC genetics 2003 Hériché JK, Ang D, Bier E, O'Farrell PH
• Cyclin B destruction triggers changes in kinetochore behavior essential for successful anaphase.
  Current biology : CB 2003 Parry DH, Hickson GR, O'Farrell PH
• The degradation of two mitotic cyclins contributes to the timing of cytokinesis.
  Current biology : CB 2003 Echard A, O'Farrell PH
• Nitric oxide-induced suspended animation promotes survival during hypoxia.
  The EMBO journal 2003 Teodoro RO, O'Farrell PH
• Anomalous centriole configurations are detected in Drosophila wing disc cells upon Cdk1 inactivation.
  Journal of cell science 2003 Vidwans SJ, Wong ML, O'Farrell PH
• Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria in Drosophila.
  Genes & development 2003 Foley E, O'Farrell PH
• Sister chromatids fail to separate during an induced endoreplication cycle in Drosophila embryos.
  Current biology : CB 2002 Vidwans SJ, DiGregorio PJ, Shermoen AW, Foat B, Iwasa J, Yakubovich N, O'Farrell PH
• Triggering the all-or-nothing switch into mitosis.
  Trends in cell biology 2001 O'Farrell PH
• Cell cycle roles for two 14-3-3 proteins during Drosophila development.
  Journal of cell science 2001 Su TT, Parry DH, Donahoe B, Chien CT, O'Farrell PH, Purdy A
• The schedule of destruction of three mitotic cyclins can dictate the timing of events during exit from mitosis.
  Current biology : CB 2001 Parry DH, O'Farrell PH
• Conserved responses to oxygen deprivation.
  The Journal of clinical investigation 2001 O'Farrell PH
• Hypoxia and nitric oxide induce a rapid, reversible cell cycle arrest of the Drosophila syncytial divisions.
  The Journal of biological chemistry 2000 DiGregorio PJ, Ubersax JA, O'Farrell PH
• Drosophila wee1 has an essential role in the nuclear divisions of early embryogenesis.
  Genetics 2000 Price D, Rabinovitch S, O'Farrell PH, Campbell SD
• Comparative genomics of the eukaryotes.
  Science (New York, N.Y.) 2000 Rubin GM, Yandell MD, Wortman JR, Gabor Miklos GL, Nelson CR, Hariharan IK, Fortini ME, Li PW, Apweiler R, Fleischmann W, Cherry JM, Henikoff S, Skupski MP, Misra S, Ashburner M, Birney E, Boguski MS,…
• Mitotic regulators govern progress through steps in the centrosome duplication cycle.
  The Journal of cell biology 1999 Vidwans SJ, Wong ML, O'Farrell PH
• Rux is a cyclin-dependent kinase inhibitor (CKI) specific for mitotic cyclin-Cdk complexes.
  Current biology : CB 1999 Foley E, O'Farrell PH, Sprenger F
• Transcribed genes are localized according to chromosomal position within polarized Drosophila embryonic nuclei.
  Current biology : CB 1999 Wilkie GS, Shermoen AW, O'Farrell PH, Davis I
• Cytoskeleton: centrosom-in absentia.
  Current biology : CB 1999 Vidwans SJ, O'Farrell PH
• Drosophila grapes/CHK1 mutants are defective in cyclin proteolysis and coordination of mitotic events.
  Current biology : CB 1999 Su TT, Campbell SD, O'Farrell PH
• Nitric oxide contributes to behavioral, cellular, and developmental responses to low oxygen in Drosophila.
  Cell 1999 Wingrove JA, O'Farrell PH
• Size control: cell proliferation does not equal growth.
  Current biology : CB 1998 Su TT, O'Farrell PH
• Exit from mitosis in Drosophila syncytial embryos requires proteolysis and cyclin degradation, and is associated with localized dephosphorylation.
  Genes & development 1998 Su TT, Sprenger F, DiGregorio PJ, Campbell SD, O'Farrell PH
• The cell cycle program in germ cells of the Drosophila embryo.
  Developmental biology 1998 Su TT, Campbell SD, O'Farrell PH
• Fluctuations in cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila.
  Current biology : CB 1998 Follette PJ, Duronio RJ, O'Farrell PH
• Chromosome association of minichromosome maintenance proteins in Drosophila endoreplication cycles.
  The Journal of cell biology 1998 Su TT, O'Farrell PH
• Mutations of the Drosophila dDP, dE2F, and cyclin E genes reveal distinct roles for the E2F-DP transcription factor and cyclin E during the G1-S transition.
  Molecular and cellular biology 1998 Duronio RJ, Bonnette PC, O'Farrell PH
• Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles.
  The Journal of cell biology 1997 Su TT, O'Farrell PH
• S-phase function of Drosophila cyclin A and its downregulation in G1 phase.
  Current biology : CB 1997 Sprenger F, Yakubovich N, O'Farrell PH
• Cloning of Drosophila MCM homologs and analysis of their requirement during embryogenesis.
  Gene 1997 Su TT, Yakubovich N, O'Farrell PH
• Limb morphogenesis: connections between patterning and growth.
  Current biology : CB 1997 Serrano N, O'Farrell PH
• Connecting cell behavior to patterning: lessons from the cell cycle.
  Cell 1997 Follette PJ, O'Farrell PH
• Cdks and the Drosophila cell cycle.
  Current opinion in genetics & development 1997 Follette PJ, O'Farrell PH
• E2F-induced S phase requires cyclin E.
  Genes & development 1996 Duronio RJ, Brook A, Dyson N, O'Farrell PH
• Drosophila Cdk8, a kinase partner of cyclin C that interacts with the large subunit of RNA polymerase II.
  Molecular biology of the cell 1996 Leclerc V, Tassan JP, O'Farrell PH, Nigg EA, Léopold P
• Drosophila MCM protein complexes.
  Molecular biology of the cell 1996 Su TT, Feger G, O'Farrell PH
• Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro.
  Molecular biology of the cell 1995 Campbell SD, Sprenger F, Edgar BA, O'Farrell PH
• A nuclear GFP that marks nuclei in living Drosophila embryos; maternal supply overcomes a delay in the appearance of zygotic fluorescence.
  Developmental biology 1995 Davis I, Girdham CH, O'Farrell PH
• Cell proliferation and DNA replication defects in a Drosophila MCM2 mutant.
  Genes & development 1995 Treisman JE, Follette PJ, O'Farrell PH, Rubin GM
• Qualifying for the license to replicate.
  Cell 1995 Su TT, Follette PJ, O'Farrell PH
• Developmental control of the G1 to S transition in Drosophila: cyclin Eis a limiting downstream target of E2F.
  Genes & development 1995 Duronio RJ, O'Farrell PH
• The transcription factor E2F is required for S phase during Drosophila embryogenesis.
  Genes & development 1995 Duronio RJ, O'Farrell PH, Xie JE, Brook A, Dyson N
• Transcriptional regulation of string (cdc25): a link between developmental programming and the cell cycle.
  Development (Cambridge, England) 1994 Edgar BA, Lehman DA, O'Farrell PH
• The making of a maggot: patterning the Drosophila embryonic epidermis.
  Current opinion in genetics & development 1994 DiNardo S, Heemskerk J, Dougan S, O'Farrell PH
• A cell-autonomous, ubiquitous marker for the analysis of Drosophila genetic mosaics.
  Developmental biology 1994 Vincent JP, Girdham CH, O'Farrell PH
• Developmental control of a G1-S transcriptional program in Drosophila.
  Development (Cambridge, England) 1994 Duronio RJ, O'Farrell PH
• Developmental biology. Unanimity waits in the wings.
  Nature 1994 O'Farrell PH
• Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis.
  Genes & development 1994 Edgar BA, Sprenger F, Duronio RJ, Leopold P, O'Farrell PH
• The use of photoactivatable reagents for the study of cell lineage in Drosophila embryogenesis.
  Methods in cell biology 1994 Girdham CH, O'Farrell PH
• A universal target sequence is bound in vitro by diverse homeodomains.
  Mechanisms of development 1993 Kalionis B, O'Farrell PH
• Maintenance of the engrailed expression pattern by Polycomb group genes in Drosophila.
  Development (Cambridge, England) 1992 Moazed D, O'Farrell PH
• Developmental biology. Big genes and little genes and deadlines for transcription.
  Nature 1992 O'Farrell PH
• Cell cycle control: many ways to skin a cat.
  Trends in cell biology 1992 O'Farrell PH
• The state of engrailed expression is not clonally transmitted during early Drosophila development.
  Cell 1992 Vincent JP, O'Farrell PH
• Progression of the cell cycle through mitosis leads to abortion of nascent transcripts.
  Cell 1991 Shermoen AW, O'Farrell PH
• An evolutionarily conserved cyclin homolog from Drosophila rescues yeast deficient in G1 cyclins.
  Cell 1991 Léopold P, O'Farrell PH
• Multiple modes of engrailed regulation in the progression towards cell fate determination.
  Nature 1991 Heemskerk J, DiNardo S, Kostriken R, O'Farrell PH
• Active repression of transcription by the engrailed homeodomain protein.
  The EMBO journal 1991 Jaynes JB, O'Farrell PH
• Exploring the role of Drosophila cyclin A in the regulation of S phase.
  Cold Spring Harbor symposia on quantitative biology 1991 Lehner CF, Yakubovich N, O'Farrell PH
• Drosophila cdc2 homologs: a functional homolog is coexpressed with a cognate variant.
  The EMBO journal 1990 Lehner CF, O'Farrell PH
• The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string.
  Cell 1990 Edgar BA, O'Farrell PH
• A synthetic homeodomain binding site acts as a cell type specific, promoter specific enhancer in Drosophila embryos.
  The EMBO journal 1990 Vincent JP, Kassis JA, O'Farrell PH
• The roles of Drosophila cyclins A and B in mitotic control.
  Cell 1990 Lehner CF, O'Farrell PH
• Directing cell division during development.
  Science (New York, N.Y.) 1989 O'Farrell PH, Edgar BA, Lakich D, Lehner CF
• Evolutionary conservation of homeodomain-binding sites and other sequences upstream and within the major transcription unit of the Drosophila segmentation gene engrailed.
  Molecular and cellular biology 1989 Kassis JA, Desplan C, Wright DK, O'Farrell PH
• Genetic control of cell division patterns in the Drosophila embryo.
  Cell 1989 Edgar BA, O'Farrell PH
• Expression and function of Drosophila cyclin A during embryonic cell cycle progression.
  Cell 1989 Lehner CF, O'Farrell PH
• Activation and repression of transcription by homoeodomain-containing proteins that bind a common site.
  Nature 1988 Jaynes JB, O'Farrell PH
• The sequence specificity of homeodomain-DNA interaction.
  Cell 1988 Desplan C, Theis J, O'Farrell PH
• Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis.
  Nature 1988 DiNardo S, Sher E, Heemskerk-Jongens J, Kassis JA, O'Farrell PH
• Temporal and spatial relationships between segmentation and homeotic gene expression in Drosophila embryos: distributions of the fushi tarazu, engrailed, Sex combs reduced, Antennapedia, and Ultrabithorax proteins.
  Genes & development 1988 Carroll SB, DiNardo S, O'Farrell PH, White RA, Scott MP
• Establishment and refinement of segmental pattern in the Drosophila embryo: spatial control of engrailed expression by pair-rule genes.
  Genes & development 1987 DiNardo S, O'Farrell PH
• Sequence conservation in the protein coding and intron regions of the engrailed transcription unit.
  The EMBO journal 1986 Kassis JA, Poole SJ, Wright DK, O'Farrell PH
• Spatial programming of gene expression in early Drosophila embryogenesis.
  Annual review of cell biology 1986 Scott MP, O'Farrell PH
• Electron microscopic heteroduplex mapping identifies regions of the engrailed locus that are conserved between Drosophila melanogaster and Drosophila virilis.
  Molecular and cellular biology 1985 Kassis JA, Wong ML, O'Farrell PH
• The Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity.
  Nature 1985 Desplan C, Theis J, O'Farrell PH
• Development of embryonic pattern in D. melanogaster as revealed by accumulation of the nuclear engrailed protein.
  Cell 1985 DiNardo S, Kuner JM, Theis J, O'Farrell PH
• Molecular cloning of engrailed: a gene involved in the development of pattern in Drosophila melanogaster.
  Cell 1985 Kuner JM, Nakanishi M, Ali Z, Drees B, Gustavson E, Theis J, Kauvar L, Kornberg T, O'Farrell PH
• Separation techniques based on the opposition of two counteracting forces to produce a dynamic equilibrium.
  Science (New York, N.Y.) 1985 O'farrell PH
• Embryonic pattern in Drosophila: the spatial distribution and sequence-specific DNA binding of engrailed protein.
  Cold Spring Harbor symposia on quantitative biology 1985 O'Farrell PH, Desplan C, DiNardo S, Kassis JA, Kuner JM, Sher E, Theis J, Wright D
• The level of expression of the rat growth hormone gene in liver tumor cells is at least eight orders of magnitude less than that in anterior pituitary cells.
  Molecular and cellular biology 1983 Ivarie RD, Schacter BS, O'Farrell PH
• A restriction map of the bacteriophage T4 genome.
  Molecular & general genetics : MGG 1980 O'Farrell PH, Kutter E, Nakanishi M
• The glucocorticoid domain of response: measurement of pleiotropic cellular responses by two-dimensional gel electrophoresis.
  Monographs on endocrinology 1979 O'Farrell PH, Ivarie RD
• Isolation and characterization of ColE1-derived plasmid copy-number mutant.
  Proceedings of the National Academy of Sciences of the United States of America 1978 Gelfand DH, Shepard HM, O'Farrell PH, Polisky B
• The suppression of defective translation by ppGpp and its role in the stringent response.
  Cell 1978 O'Farrell PH
• The glucocorticoid domain: steroid-mediated changes in the rate of synthesis of rat hepatoma proteins.
  Cell 1978 Ivarie RD, O'Farrell PH
• High resolution two-dimensional electrophoresis of basic as well as acidic proteins.
  Cell 1977 O'Farrell PZ, Goodman HM, O'Farrell PH
• Mutations causing charge alterations in regulatory subunits of the cAMP-dependent protein kinase of cultured S49 lymphoma cells.
  Cell 1977 Steinberg RA, O'Farrell PH, Friedrich U, Coffino P
• Two-dimensional polyacrylamide gel electrophoretic fractionation.
  Methods in cell biology 1977 O'Farrell PH, O'Farrell PZ
• High resolution two-dimensional electrophoresis of proteins.
  The Journal of biological chemistry 1975 O'Farrell PH
• Estrogen binding in the uteri of mammals with delayed implantation.
  Endocrinology 1971 O'Farrell PH, Daniel JC