Rafael A. Fissore

Rafael A. Fissore


Pronouns: he, him, his

Office phone: 413-545-5548

Fax: 413-545-6326

Email: rfissore [at] vasci [dot] umass [dot] edu

Office location: 427E ISB

Ph.D.: University of Massachusetts, 1993
Postdoctoral Training: Harvard Medical School
Distinguished Faculty Lecturer  2008
Chancellor’s Medal 2008
CFNR Outstanding Research Award 2002

ANIML SCI 521 H04 
- Honors Colloquium - Physiology of Reproduction

Ca2+ Release Mechanisms in Mammalian Eggs During Maturation and Fertilization

My laboratory is interested in understanding the mechanism by which the sperm is able to induce activation and trigger development in mammalian eggs. It is widely known that at fertilization the sperm induces Ca2+ oscillations and this Ca2+ release is the signal responsible for triggering the majority of events that culminate in embryonic development. However, how the sperm first signals Ca2+ release and oscillations in eggs remains to be elucidated. Therefore, a main topic of research in our laboratory is to identify the pathway, and isolate the molecule(s), responsible for this specific event of Ca2+ signaling. We are using several techniques to approach this question including intracellular Ca2+ signaling, in vitro fertilization, intracytoplasmic sperm injection (ICSI), protein purification using column chromatography, and the application of multiple agonists/antagonists of common signal transduction pathways.

In another line of research, we are trying to understand the regulation of Ca2+ release through the inositol 1,4,5-triphosphate receptor (IP3R). This receptor is thought to mediate the totality of Ca2+ release during fertilization in mammals. Furthermore, it undergoes specific degradation as the first cell cycle progresses, and this degradation appears to be exclusively associated with IP3 production. We are investigating whether or not changes in the cell cycle affect the conductivity of the receptor, and the pathway by which the receptor is degraded in mammalian eggs. To address these questions we are using kinase assays, western blotting, microinjection and inhibitors of the proteasome, expression of IP3R mRNAs and mutations of the receptor. We have also recently identified a new inhibitor of the IPR3R-1, KN-93, and are in the process of characterizing its mechanism of action.

Injection of SF induces egg activation

Navarrete FA, Aguila L, Martin-Hidalgo D, Tourzani DA, Luque GM, Ardestani G, García-Vázquez FA, Levin LR, Buck J, Darszon A et al..  2019.  Transient Sperm Starvation Improves the Outcome of Assisted Reproductive Technologies. Frontiers in Cell and Developmental Biology. 7
Ardestani G, West M, Maresca TJ, Fissore RA, Stratton MM.  2018.  Development of a genetically encoded sensor for endogenous CaMKII activity.
Águila L, Felmer R, Arias ME, Navarrete F, Martin-Hidalgo D, Lee HC, Visconti P, Fissore R.  2017.  Defective sperm head decondensation undermines the success of ICSI in the bovine. Reproduction. 154:207–218.
Hachem A, Godwin J, Ruas M, Lee HC, Buitrago MF, Ardestani G, Bassett A, Fox S, Navarrete F, De Sutter P et al..  2017.  PLCz is the physiological trigger of the Ca 2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence. Development. 144:2914–2924.
Carvacho I, Ardestani G, Lee HC, McGarvey K, Fissore RA, Lykke-Hartmann K.  2016.  TRPM7-like channels are functionally expressed in oocytes and modulate post-fertilization embryo development in mouse. Scientific Reports. 6
Navarrete FA, Alvau A, Lee HC, Levin LR, Buck J, Leon PM-D, Santi CM, Krapf D, Mager J, Fissore RA et al..  2016.  Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models. Scientific Reports. 6
Bello OD, Cappa AI, de Paola M, Zanetti MN, Fukuda M, Fissore RA, Mayorga LS, Michaut MA.  2016.  Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs. Experimental Cell Research. 347:42–51.
Coutton C, Fissore RA, Palermo GD, Stouffs K, Touré A.  2016.  Male Infertility: Genetics, Mechanism, and Therapies. BioMed Research International. 2016:1–1.
Lee HC, Yoon S-Y, Lykke-Hartmann K, Fissore RA, Carvacho I.  2016.  TRPV3 channels mediate Ca2+ influx induced by 2-APB in mouse eggs. Cell Calcium. 59:21–31.
Escoffier J, Lee HC, Yassine S, Zouari R, Martinez G, Karaouzène T, Coutton C, Kherraf Z-eddine, Halouani L, Triki C et al..  2015.  Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP. Human Molecular Genetics. 25:878–891.
Kornbluth S, Fissore R.  2015.  Vertebrate Reproduction. Cold Spring Harbor Perspectives in Biology. 7:a006064.
Chithiwala ZH, Lee HC, Hill DL, Jellerette-Nolan T, Fissore R, Grow D, Dumesic DA.  2015.  Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report. Journal of Assisted Reproduction and Genetics. 32:1415–1419.
Escoffier J, Yassine S, Lee HC, Martinez G, Delaroche J, Coutton C, Karaouzène T, Zouari R, Metzler-Guillemain C, Pernet-Gallay K et al..  2014.  Subcellular localization of phospholipase C-zeta in human sperm and its absence in DPY19L2-deficient sperm are consistent with its role in oocyte activation. {MHR}: Basic science of reproductive medicine. 21:157–168.
Yassine S, Escoffier J, Martinez G, Coutton C, Karaouzène T, Zouari R, Ravanat J-L, Metzler-Guillemain C, Lee HC, Fissore R et al..  2014.  Dpy19l2-deficient globozoospermic sperm display altered genome packaging and DNA damage that compromises the initiation of embryo development. MHR: Basic science of reproductive medicine. 21:169–185.
Sunryd JC, Cheon B, Graham JB, Giorda KM, Fissore RA, Hebert DN.  2014.  TMTC1 and TMTC2 Are Novel Endoplasmic Reticulum Tetratricopeptide Repeat-containing Adapter Proteins Involved in Calcium Homeostasis. Journal of Biological Chemistry. 289:16085–16099.
Lee HC, Arny M, Grow D, Dumesic D, Fissore RA, Jellerette-Nolan T.  2014.  Protein phospholipase C Zeta1 expression in patients with failed ICSI but with normal sperm parameters. Journal of Assisted Reproduction and Genetics. 31:749–756.
Carvacho I, Lee H C, Fissore R A, Clapham D E.  2013.  TRPV3 Channels Mediate Strontium-Induced Mouse-Egg Activation. Cell Reports. 5:1375–1386.
Wakai T, Zhang N, Vangheluwe P, Fissore RA.  2013.  Regulation of endoplasmic reticulum Ca 2+ oscillations in mammalian eggs. Journal of Cell Science. 126:5714–5724.
McCoy F, Darbandi R, Lee H C, Bharatham K, Moldoveanu T, Grace CR, Dodd K, Lin W, Chen S-I, Tangallapally R P et al..  2013.  Metabolic Activation of CaMKII by Coenzyme A. Molecular Cell. 52:325–339.
Villaverde AIBS, Fioratti EG, Fissore RA, He C, Lee HC, Souza FF, Landim-Alvarenga FC, Lopes MD.  2013.  Identification of phospholipase C zeta in normospermic and teratospermic domestic cat sperm. Theriogenology. 80:722–729.
Sato K, Wakai T, Seita Y, Takizawa A, Fissore RA, Ito J, Kashiwazaki N.  2013.  Molecular characteristics of horse phospholipase C zeta (PLCzeta). Animal Science Journal. 84:359–368.
Cheon B, Lee H-C, Wakai T, Fissore RA.  2013.  Ca2+ influx and the store-operated Ca2+ entry pathway undergo regulation during mouse oocyte maturation. Molecular Biology of the Cell. 24:1396–1410.
Wakai T, Vanderheyden V, Yoon S-Y, Cheon B, Zhang N, Parys JB, Fissore RA.  2012.  Regulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation.. Journal of cellular physiology. 227(2):705-17.
Kashir J, Konstantinidis M, Jones C, Lemmon B, Lee HC, Hamer R, Heindryckx B, Deane CM, De Sutter P, Fissore RA et al..  2012.  A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility.. Human reproduction (Oxford, England). 27(1):222-31.
Coward K, Ponting CP, Zhang N, Young C, Huang C-J, Chou C-M, Kashir J, Fissore RA, Parrington J.  2011.  Identification and functional analysis of an ovarian form of the egg activation factor phospholipase C zeta (PLCζ) in pufferfish.. Molecular reproduction and development. 78(1):48-56.
Ito J, Parrington J, Fissore RA.  2011.  PLCζ and its role as a trigger of development in vertebrates.. Molecular reproduction and development. 78(10-11):846-53.
Zhang N, Wakai T, Fissore RA.  2011.  Caffeine alleviates the deterioration of Ca2+ release mechanisms and fragmentation of in vitro-aged mouse eggs. Molecular Reproduction and Development. 78(9):684-701.
Kim BY, Yoon S-Y, Cha SK, Kwak KH, Fissore RA, Parys JB, Yoon TK, Lee DR.  2011.  Alterations in calcium oscillatory activity in vitrified mouse eggs impact on egg quality and subsequent embryonic development.. Pflügers Archiv : European journal of physiology. 461(5):515-26.
Kashir J, Jones C, Lee HC, Rietdorf K, Nikiforaki D, Durrans C, Ruas M, Tee ST, Heindryckx B, Galione A et al..  2011.  Loss of activity mutations in phospholipase C zeta (PLCζ) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes.. Human reproduction (Oxford, England). 26(12):3372-87.
Silvestre F, Boni R, Fissore RA, Tosti E.  2011.  Ca2+ signaling during maturation of cumulus-oocyte complex in mammals.. Molecular reproduction and development. 78(10-11):744-56.
Wakai T, Vanderheyden V, Fissore RA.  2011.  Ca2+ signaling during mammalian fertilization: requirements, players, and adaptations.. Cold Spring Harbor perspectives in biology. 3(4)
Coward K, Ponting CP, Zhang N, Young C, Huang C-J, Chou C-M, Kashir J, Fissore RA, Parrington J.  2010.  Identification and functional analysis of an ovarian form of the egg activation factor phospholipase C Zeta (PLCζ) in pufferfish.. Molecular reproduction and development.
Cooney MA, Malcuit C, Cheon B, Holland MK, Fissore RA, D'Cruz NT.  2010.  Species-specific differences in the activity and nuclear localization of murine and bovine phospholipase C zeta 1.. Biology of reproduction. 83(1):92-101.
Ito J, Yoshida T, Kasai Y, Wakai T, Parys JB, Fissore RA, Kashiwazaki N.  2010.  Phosphorylation of inositol 1,4,5-triphosphate receptor 1 during in vitro maturation of porcine oocytes.. Animal science journal = Nihon chikusan Gakkaihō. 81(1):34-41.
Taylor SL, Yoon SY, Morshedi MS, Lacey DR, Jellerette T, Fissore RA, Oehninger S.  2010.  Complete globozoospermia associated with PLCζ deficiency treated with calcium ionophore and ICSI results in pregnancy.. Reproductive biomedicine online. 20(4):559-64.
Lee B, Yoon S-Y, Malcuit C, Parys JB, Fissore RA.  2010.  Inositol 1,4,5-trisphosphate receptor 1 degradation in mouse eggs and impact on [Ca2+]i oscillations.. Journal of cellular physiology. 222(1):238-47.
Sosnik J, Miranda PV, Spiridonov NA, Yoon S-Y, Fissore RA, Johnson GR, Visconti PE.  2009.  Tssk6 is required for Izumo relocalization and gamete fusion in the mouse.. Journal of cell science. 122(Pt 15):2741-9.
Vanderheyden V, Wakai T, Bultynck G, De Smedt H, Parys JB, Fissore RA.  2009.  Regulation of inositol 1,4,5-trisphosphate receptor type 1 function during oocyte maturation by MPM-2 phosphorylation.. Cell calcium. 46(1):56-64.
Yoon S-Y, Jellerette T, Salicioni AM, Lee HC, Yoo M-S, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE et al..  2008.  Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development.. The Journal of clinical investigation. 118(11):3671-81.
Ito J, Yoon S-Y, Lee B, Vanderheyden V, Vermassen E, Wojcikiewicz R, Alfandari D, De Smedt H, Parys JB, Fissore RA.  2008.  Inositol 1,4,5-trisphosphate receptor 1, a widespread Ca2+ channel, is a novel substrate of polo-like kinase 1 in eggs.. Developmental biology. 320(2):402-13.
Kurokawa M, Yoon SY, Alfandari D, Fukami K, Sato K-ichi, Fissore RA.  2007.  Proteolytic processing of phospholipase Czeta and [Ca2+]i oscillations during mammalian fertilization.. Developmental biology. 312(1):407-18.
Lee B, Vermassen E, Yoon S-Y, Vanderheyden V, Ito J, Alfandari D, De Smedt H, Parys JB, Fissore RA.  2006.  Phosphorylation of IP3R1 and the regulation of [Ca2+]i responses at fertilization: a role for the MAP kinase pathway.. Development (Cambridge, England). 133(21):4355-65.
Kurokawa M, Sato K-ichi, Wu H, He C, Malcuit C, Black SJ, Fukami K, Fissore RA.  2005.  Functional, biochemical, and chromatographic characterization of the complete [Ca2+]i oscillation-inducing activity of porcine sperm.. Developmental biology. 285(2):376-92.
Johnson SA, Marín-Bivens CL, Miele M, Coyle CA, Fissore R, Good DJ.  2004.  The Nhlh2 transcription factor is required for female sexual behavior and reproductive longevity.. Hormones and behavior. 46(4):420-7.
Gordo AC, Rodrigues P, Kurokawa M, Jellerette T, Exley GE, Warner C, Fissore R.  2002.  Intracellular calcium oscillations signal apoptosis rather than activation in in vitro aged mouse eggs.. Biology of reproduction. 66(6):1828-37.
Morgan G, Smith S, Pak J, Marshak-Rothstein A, Fissore R, Osborne B.  1999.  Characterization of a mutant T-cell hybridoma line with defects in the TCR-mediated apoptotic pathway.. Cell death and differentiation. 6(1):36-47.
Wu H, He CL, Jehn B, Black SJ, Fissore RA.  1998.  Partial characterization of the calcium-releasing activity of porcine sperm cytosolic extracts.. Developmental biology. 203(2):369-81.
Fissore RA, Dobrinsky JR, Balise JJ, Duby RT, Robl JM.  1992.  Patterns of intracellular Ca2+ concentrations in fertilized bovine eggs.. Biology of reproduction. 47(6):960-9.
Name Phone Office
Lopes , Emily M.Graduate student - MCB program 413-545-5547 ISB 465A
Carpentiero , Francesca Graduate Student, ABBS Program 413-545-5547 ISB 465A
Thaker , Nidhi Graduate Student, MCB Program 413-545-5547 ISB 465A
Gupta , Neha Ph.D Candidate ABBS 413-545-5547 ISB 465A