Marco Conti, MD

Professor
Department of Obstetrics Gynecology & Reproductive Sciences
Center for Reproductive Sciences

Dr. Conti's research focuses on signal transduction required for germ cell development. Over the past 15 years, we have charted signaling pathways controlling oocyte meiotic maturation and competence for development into an embryo. We have identified critical signals arising in the somatic cells at the time of ovulation that are required to establish oocyte developmental competence. Genetic models that disrupt these pathways and compromise developmental competence and early embryo development have been established.

Focus of the experiments is on understanding how disruption of developmental competence in these genetic models is reflected in the pattern of recruitment of maternal mRNA translation into proteins critical for nuclear reprogramming and early embryo development. This strategy has the potential to identify components critical for the epigenetic regulations required for early embryo development. The impact of this research program on stem cell research is twofold. These studies are relevant to the understanding of the mechanisms controlling cell replication and nuclear reprogramming during preimplantation embryo development and lineage specification.

A better understanding of the biochemical mechanisms controlling oocyte maturation is essential for successful development of embryonic stem cells into artificial gametes. In addition, they will provide insights into mechanisms necessary for successful somatic nuclear transfer critical to the derivation of hESC for therapeutic use.

Research Summary: 
Mechanisms of Action of Peptide Hormones and Growth Factors
Publications: 

Phosphodiesterases 4B and 4D Differentially Regulate cAMP Signaling in Calcium Handling Microdomains of Mouse Hearts.

Cells

Kraft AE, Bork NI, Subramanian H, Pavlaki N, Failla AV, Zobiak B, Conti M, Nikolaev VO

Multiple intersecting pathways are involved in the phosphorylation of CPEB1 to activate translation during mouse oocyte meiosis.

bioRxiv : the preprint server for biology

Kunitomi C, Romero M, Daldello EM, Schindler K, Conti M

A genome-wide perspective of the maternal mRNA translation program during oocyte development.

Seminars in cell & developmental biology

Conti M, Kunitomi C

Author Correction: CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging.

Nature communications

Takahashi N, Franciosi F, Daldello EM, Luong XG, Althoff P, Wang X, Conti M

CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging.

Nature communications

Takahashi N, Franciosi F, Daldello EM, Luong XG, Althoff P, Wang X, Conti M

A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases.

Science translational medicine

Ghigo A, Murabito A, Sala V, Pisano AR, Bertolini S, Gianotti A, Caci E, Montresor A, Premchandar A, Pirozzi F, Ren K, Della Sala A, Mergiotti M, Richter W, de Poel E, Matthey M, Caldrer S, Cardone RA, Civiletti F, Costamagna A, Quinney NL, Butnarasu C, Visentin S, Ruggiero MR, Baroni S, Crich SG, Ramel D, Laffargue M, Tocchetti CG, Levi R, Conti M, Lu XY, Melotti P, Sorio C, De Rose V, Facchinetti F, Fanelli V, Wenzel D, Fleischmann BK, Mall MA, Beekman J, Laudanna C, Gentzsch M, Lukacs GL, Pedemonte N, Hirsch E

The H3.3 chaperone Hira complex orchestrates oocyte developmental competence.

Development (Cambridge, England)

Smith R, Susor A, Ming H, Tait J, Conti M, Jiang Z, Lin CJ

Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay.

Journal of visualized experiments : JoVE

Costermans NGJ, Daldello EM, Marathe RJ, Conti M

Genome-wide analysis reveals a switch in the translational program upon oocyte meiotic resumption.

Nucleic acids research

Luong XG, Daldello EM, Rajkovic G, Yang CR, Conti M

The RNA-binding protein DAZL functions as repressor and activator of mRNA translation during oocyte maturation.

Nature communications

Yang CR, Rajkovic G, Daldello EM, Luong XG, Chen J, Conti M

Cyclin B2 is required for progression through meiosis in mouse oocytes.

Development (Cambridge, England)

Daldello EM, Luong XG, Yang CR, Kuhn J, Conti M

Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated macrophages.

Innate immunity

Yang JX, Hsiung TC, Weng FC, Ding SL, Wu CP, Conti M, Chuang TH, Catherine Jin SL

Profiling Maternal mRNA Translation During Oocyte Development.

Methods in molecular biology (Clifton, N.J.)

Martins JPS, Conti M

Atropine augments cardiac contractility by inhibiting cAMP-specific phosphodiesterase type 4.

Scientific reports

Perera RK, Fischer TH, Wagner M, Dewenter M, Vettel C, Bork NI, Maier LS, Conti M, Wess J, El-Armouche A, Hasenfuß G, Nikolaev VO

Cyclin A2 modulates kinetochore-microtubule attachment in meiosis II.

The Journal of cell biology

Zhang QH, Yuen WS, Adhikari D, Flegg JA, FitzHarris G, Conti M, Sicinski P, Nabti I, Marangos P, Carroll J

Maternal mRNAs with distinct 3' UTRs define the temporal pattern of Ccnb1 synthesis during mouse oocyte meiotic maturation.

Genes & development

Yang Y, Yang CR, Han SJ, Daldello EM, Cho A, Martins JPS, Xia G, Conti M

Functional selectivity of GPCR-directed drug action through location bias.

Nature chemical biology

Irannejad R, Pessino V, Mika D, Huang B, Wedegaertner PB, Conti M, von Zastrow M

Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages.

Scientific reports

Yang JX, Hsieh KC, Chen YL, Lee CK, Conti M, Chuang TH, Wu CP, Jin SC

Dynamic secretion during meiotic reentry integrates the function of the oocyte and cumulus cells.

Proceedings of the National Academy of Sciences of the United States of America

Cakmak H, Franciosi F, Zamah AM, Cedars MI, Conti M

DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation.

Journal of cell science

Sousa Martins JP, Liu X, Oke A, Arora R, Franciosi F, Viville S, Laird DJ, Fung JC, Conti M

A CaMKII/PDE4D negative feedback regulates cAMP signaling.

Proceedings of the National Academy of Sciences of the United States of America

Mika D, Richter W, Conti M

The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases (PDE4s).

The Biochemical journal

Xie M, Blackman B, Scheitrum C, Mika D, Blanchard E, Lei T, Conti M, Richter W

Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior.

Psychopharmacology

Hansen RT, Conti M, Zhang HT

Control of cytoplasmic and nuclear protein kinase A by phosphodiesterases and phosphatases in cardiac myocytes.

Cardiovascular research

Haj Slimane Z, Bedioune I, Lechêne P, Varin A, Lefebvre F, Mateo P, Domergue-Dupont V, Dewenter M, Richter W, Conti M, El-Armouche A, Zhang J, Fischmeister R, Vandecasteele G

PDE4B mediates local feedback regulation of ß1-adrenergic cAMP signaling in a sarcolemmal compartment of cardiac myocytes.

Journal of cell science

Mika D, Richter W, Westenbroek RE, Catterall WA, Conti M

Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes.

Nature cell biology

Chen J, Torcia S, Xie F, Lin CJ, Cakmak H, Franciosi F, Horner K, Onodera C, Song JS, Cedars MI, Ramalho-Santos M, Conti M

Anchored PDE4 regulates chloride conductance in wild-type and ?F508-CFTR human airway epithelia.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Blanchard E, Zlock L, Lao A, Mika D, Namkung W, Xie M, Scheitrum C, Gruenert DC, Verkman AS, Finkbeiner WE, Conti M, Richter W

PDE4 as a target for cognition enhancement.

Expert opinion on therapeutic targets

Richter W, Menniti FS, Zhang HT, Conti M

ß1-adrenergic receptor antagonists signal via PDE4 translocation.

EMBO reports

Richter W, Mika D, Blanchard E, Day P, Conti M

Cdc25A activity is required for the metaphase II arrest in mouse oocytes.

Journal of cell science

Oh JS, Susor A, Schindler K, Schultz RM, Conti M

A novel loss-of-function mutation in Npr2 clarifies primary role in female reproduction and reveals a potential therapy for acromesomelic dysplasia, Maroteaux type.

Human molecular genetics

Geister KA, Brinkmeier ML, Hsieh M, Faust SM, Karolyi IJ, Perosky JE, Kozloff KM, Conti M, Camper SA

Phosphoinositide 3-kinase ? protects against catecholamine-induced ventricular arrhythmia through protein kinase A-mediated regulation of distinct phosphodiesterases.

Circulation

Ghigo A, Perino A, Mehel H, Zahradníková A, Morello F, Leroy J, Nikolaev VO, Damilano F, Cimino J, De Luca E, Richter W, Westenbroek R, Catterall WA, Zhang J, Yan C, Conti M, Gomez AM, Vandecasteele G, Hirsch E, Fischmeister R

Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias.

Journal of the American College of Cardiology

Molina CE, Leroy J, Richter W, Xie M, Scheitrum C, Lee IO, Maack C, Rucker-Martin C, Donzeau-Gouge P, Verde I, Llach A, Hove-Madsen L, Conti M, Vandecasteele G, Fischmeister R

Amphiregulin promotes the maturation of oocytes isolated from the small antral follicles of the rhesus macaque.

Human reproduction (Oxford, England)

Peluffo MC, Ting AY, Zamah AM, Conti M, Stouffer RL, Zelinski MB, Hennebold JD

Novel signaling mechanisms in the ovary during oocyte maturation and ovulation.

Molecular and cellular endocrinology

Conti M, Hsieh M, Zamah AM, Oh JS

Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca2+ release and cardiac contractility, independently of L-type Ca2+ current.

Circulation research

Beca S, Helli PB, Simpson JA, Zhao D, Farman GP, Jones P, Tian X, Wilson LS, Ahmad F, Chen SRW, Movsesian MA, Manganiello V, Maurice DH, Conti M, Backx PH

Phosphodiesterase 4B in the cardiac L-type Ca²? channel complex regulates Ca²? current and protects against ventricular arrhythmias in mice.

The Journal of clinical investigation

Leroy J, Richter W, Mika D, Castro LR, Abi-Gerges A, Xie M, Scheitrum C, Lefebvre F, Schittl J, Mateo P, Westenbroek R, Catterall WA, Charpentier F, Conti M, Fischmeister R, Vandecasteele G

Genome-wide analysis of translation reveals a critical role for deleted in azoospermia-like (Dazl) at the oocyte-to-zygote transition.

Genes & development

Chen J, Melton C, Suh N, Oh JS, Horner K, Xie F, Sette C, Blelloch R, Conti M

PDE4D and PDE4B function in distinct subcellular compartments in mouse embryonic fibroblasts.

The Journal of biological chemistry

Blackman BE, Horner K, Heidmann J, Wang D, Richter W, Rich TC, Conti M

Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Li YF, Cheng YF, Huang Y, Conti M, Wilson SP, O'Donnell JM, Zhang HT

Conserved expression and functions of PDE4 in rodent and human heart.

Basic research in cardiology

Richter W, Xie M, Scheitrum C, Krall J, Movsesian MA, Conti M

Phosphodiesterase 4B is essential for T(H)2-cell function and development of airway hyperresponsiveness in allergic asthma.

The Journal of allergy and clinical immunology

Jin SL, Goya S, Nakae S, Wang D, Bruss M, Hou C, Umetsu D, Conti M

Lack of functional pregnancy-associated plasma protein-A (PAPPA) compromises mouse ovarian steroidogenesis and female fertility.

Biology of reproduction

Nyegaard M, Overgaard MT, Su YQ, Hamilton AE, Kwintkiewicz J, Hsieh M, Nayak NR, Conti M, Conover CA, Giudice LC

Decreased expression and activity of cAMP phosphodiesterases in cardiac hypertrophy and its impact on beta-adrenergic cAMP signals.

Circulation research

Abi-Gerges A, Richter W, Lefebvre F, Mateo P, Varin A, Heymes C, Samuel JL, Lugnier C, Conti M, Fischmeister R, Vandecasteele G

Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes.

Biology of reproduction

Vaccari S, Weeks JL, Hsieh M, Menniti FS, Conti M

Growth factors and the development and function of the reproductive organs.

Seminars in reproductive medicine

Guidice LC, Conti M

From stem cells to germ cells and back again.

Nature medicine

Conti M, Giudice L

Critical role of PDE4D in beta2-adrenoceptor-dependent cAMP signaling in mouse embryonic fibroblasts.

The Journal of biological chemistry

Bruss MD, Richter W, Horner K, Jin SL, Conti M

Soluble adenylyl cyclase is not required for axon guidance to netrin-1.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Moore SW, Lai Wing Sun K, Xie F, Barker PA, Conti M, Kennedy TE

PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia.

Schizophrenia research

Fatemi SH, King DP, Reutiman TJ, Folsom TD, Laurence JA, Lee S, Fan YT, Paciga SA, Conti M, Menniti FS

Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases.

Circulation research

Leroy J, Abi-Gerges A, Nikolaev VO, Richter W, Lechêne P, Mazet JL, Conti M, Fischmeister R, Vandecasteele G

Luteinizing hormone signaling in preovulatory follicles involves early activation of the epidermal growth factor receptor pathway.

Molecular endocrinology (Baltimore, Md.)

Panigone S, Hsieh M, Fu M, Persani L, Conti M

Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4.

The EMBO journal

Richter W, Day P, Agrawal R, Bruss MD, Granier S, Wang YL, Rasmussen SG, Horner K, Wang P, Lei T, Patterson AJ, Kobilka B, Conti M

The mouse polyubiquitin gene Ubb is essential for meiotic progression.

Molecular and cellular biology

Ryu KY, Sinnar SA, Reinholdt LG, Vaccari S, Hall S, Garcia MA, Zaitseva TS, Bouley DM, Boekelheide K, Handel MA, Conti M, Kopito RR

Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B).

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Zhang HT, Huang Y, Masood A, Stolinski LR, Li Y, Zhang L, Dlaboga D, Jin SL, Conti M, O'Donnell JM

Differential expression and function of phosphodiesterase 4 (PDE4) subtypes in human primary CD4+ T cells: predominant role of PDE4D.

Journal of immunology (Baltimore, Md. : 1950)

Peter D, Jin SL, Conti M, Hatzelmann A, Zitt C

Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors.

The Journal of biological chemistry

Lee JH, Richter W, Namkung W, Kim KH, Kim E, Conti M, Lee MG

Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation.

Molecular and cellular biology

Hsieh M, Lee D, Panigone S, Horner K, Chen R, Theologis A, Lee DC, Threadgill DW, Conti M

Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation.

The EMBO journal

Han SJ, Vaccari S, Nedachi T, Andersen CB, Kovacina KS, Roth RA, Conti M

Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near the plasma membrane of HEK-293 cells.

American journal of physiology. Cell physiology

Rich TC, Xin W, Mehats C, Hassell KA, Piggott LA, Le X, Karpen JW, Conti M

Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization.

Developmental biology

Xie F, Garcia MA, Carlson AE, Schuh SM, Babcock DF, Jaiswal BS, Gossen JA, Esposito G, van Duin M, Conti M

A specific pattern of phosphodiesterases controls the cAMP signals generated by different Gs-coupled receptors in adult rat ventricular myocytes.

Circulation research

Rochais F, Abi-Gerges A, Horner K, Lefebvre F, Cooper DM, Conti M, Fischmeister R, Vandecasteele G

Signaling pathways for modulation of mouse sperm motility by adenosine and catecholamine agonists.

Biology of reproduction

Schuh SM, Carlson AE, McKnight GS, Conti M, Hille B, Babcock DF

Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias.

Cell

Lehnart SE, Wehrens XH, Reiken S, Warrier S, Belevych AE, Harvey RD, Richter W, Jin SL, Conti M, Marks AR

AKAP3 selectively binds PDE4A isoforms in bovine spermatozoa.

Biology of reproduction

Bajpai M, Fiedler SE, Huang Z, Vijayaraghavan S, Olson GE, Livera G, Conti M, Carr DW

Wee1B is an oocyte-specific kinase involved in the control of meiotic arrest in the mouse.

Current biology : CB

Han SJ, Chen R, Paronetto MP, Conti M

G-protein-coupled receptor signaling and the EGF network in endocrine systems.

Trends in endocrinology and metabolism: TEM

Hsieh M, Conti M

Specific role of phosphodiesterase 4B in lipopolysaccharide-induced signaling in mouse macrophages.

Journal of immunology (Baltimore, Md. : 1950)

Jin SL, Lan L, Zoudilova M, Conti M

Role of the epidermal growth factor network in ovarian follicles.

Molecular endocrinology (Baltimore, Md.)

Conti M, Hsieh M, Park JY, Su YQ

Phosphodiesterase 4D is required for beta2 adrenoceptor subtype-specific signaling in cardiac myocytes.

Proceedings of the National Academy of Sciences of the United States of America

Xiang Y, Naro F, Zoudilova M, Jin SL, Conti M, Kobilka B

Generation of PDE4 knockout mice by gene targeting.

Methods in molecular biology (Clifton, N.J.)

Jin SL, Latour AM, Conti M

Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site of inflammation.

Journal of immunology (Baltimore, Md. : 1950)

Ariga M, Neitzert B, Nakae S, Mottin G, Bertrand C, Pruniaux MP, Jin SL, Conti M

Phosphodiesterase 4D forms a cAMP diffusion barrier at the apical membrane of the airway epithelium.

The Journal of biological chemistry

Barnes AP, Livera G, Huang P, Sun C, O'Neal WK, Conti M, Stutts MJ, Milgram SL

Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility.

The Journal of clinical investigation

Masciarelli S, Horner K, Liu C, Park SH, Hinckley M, Hockman S, Nedachi T, Jin C, Conti M, Manganiello V

Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect.

Proceedings of the National Academy of Sciences of the United States of America

Esposito G, Jaiswal BS, Xie F, Krajnc-Franken MA, Robben TJ, Strik AM, Kuil C, Philipsen RL, van Duin M, Conti M, Gossen JA, Jaiswal BS

EGF-like growth factors as mediators of LH action in the ovulatory follicle.

Science (New York, N.Y.)

Park JY, Su YQ, Ariga M, Law E, Jin SL, Conti M

PDE4D plays a critical role in the control of airway smooth muscle contraction.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Méhats C, Jin SL, Wahlstrom J, Law E, Umetsu DT, Conti M

Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoa.

Proceedings of the National Academy of Sciences of the United States of America

Jaiswal BS, Conti M

Rodent oocytes express an active adenylyl cyclase required for meiotic arrest.

Developmental biology

Horner K, Livera G, Hinckley M, Trinh K, Storm D, Conti M

IGF-I-induced differentiation of L6 myogenic cells requires the activity of cAMP-phosphodiesterase.

Molecular biology of the cell

De Arcangelis V, Coletti D, Conti M, Lagarde M, Molinaro M, Adamo S, Nemoz G, Naro F

Phosphodiesterase regulation is critical for the differentiation and pattern of gene expression in granulosa cells of the ovarian follicle.

Molecular endocrinology (Baltimore, Md.)

Park JY, Richard F, Chun SY, Park JH, Law E, Horner K, Jin SL, Conti M

Desensitization of Gs-coupled receptor signaling by constitutively active mutants of the human lutropin/choriogonadotropin receptor.

The Journal of clinical endocrinology and metabolism

Shinozaki H, Butnev V, Tao YX, Ang KL, Conti M, Segaloff DL

Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling.

The Journal of biological chemistry

Conti M, Richter W, Mehats C, Livera G, Park JY, Jin C

Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats.

Proceedings of the National Academy of Sciences of the United States of America

Paruthiyil S, eL Majdoubi M, Conti M, Weiner RI

Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses.

Proceedings of the National Academy of Sciences of the United States of America

Jin SL, Conti M

Role of cyclic nucleotide signaling in oocyte maturation.

Molecular and cellular endocrinology

Conti M, Andersen CB, Richard F, Mehats C, Chun SY, Horner K, Jin C, Tsafriri A

Cyclic nucleotide phosphodiesterases and their role in endocrine cell signaling.

Trends in endocrinology and metabolism: TEM

Mehats C, Andersen CB, Filopanti M, Jin SL, Conti M

Differential expression of non-muscle myosin heavy chain genes during Xenopus embryogenesis.

Mechanisms of development

Bhatia-Dey N, Taira M, Conti MA, Nooruddin H, Adelstein RS

Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors.

The Journal of biological chemistry

Kim YH, Choi CY, Lee SJ, Conti MA, Kim Y

Phosphorylation of vertebrate nonmuscle myosin heavy chains by protein kinase C.

Advances in second messenger and phosphoprotein research

Adelstein RS, Peleg I, Ludowyke R, Kawamoto S, Conti MA