Isabella Caniggia

Senior Investigator, Scientist, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital

Research Synopsis

Research Interests:  Understanding the cellular and molecular mechanisms underlying the etio-pathogenesis of pregnancy related disorders. The overall aim of my research program is to understand the cellular and molecular physiological mechanisms regulating normal and pathological placental development with the long-term objective to use the information to develop new diagnostic tests and potential therapeutic strategies.

Keywords (all that apply): cell biology, diabetes, development, epigenetics, genetic expression, growth factors, human models, hypertension, insulin resistance, molecular biology, oxidative stress, protein trafficking, receptors, reproductive biology, shphingolipid metabolism, shphingosine-1-phosphate signaling, transcription and transfection, mouse models

Detailed Description: oxygen and oxygen sensing in the human placenta in physiological and pathological conditions, polarity, fusion, cell differentiation, cell death, TGFB signalling, autophagy, sphingolipid metabolism, cell cycle, epigenetics, sphinigloionds, Bcl-2 family members, gestational diseases, preeclampsia, IUGR, pregnancy.

Methods Used: Elisa, gene expression analysis, immunohistochemistry, immunocytochemistry, mass spectrometry, microarrays, proteomics, qRT-PCR, RIA, RT-PCR, signal transduction characterization, siRNA, wester blot

Equipment Used: Amplifer, analytical balances, benchtop microcentrifuge, blotting apparatus, culture incubators, dissecting microscope (benchtop microscope), gel apparatus, low and ultraflow freezers, microwave oven, mini vortexer, microplate shaker, Ph meter, ProBlot hybridization oven, real-tiem/thermocycler, setups for electrophoresis, shaker

PRESENT TRAINEES                                                                                                      

Sruthi Alahari, PhD, Department of Physiology, University of Toronto.
Project: Novel mechanisms of HIF-1a regulation in placental pathologies

Jonathan Ausman, MSc, Institute of Medical Science, University of Toronto
Project: Exploring mitochondrial dynamics in the pathogenesis of placental disease

Liane Bailey, MSc, Institute of Medical Science, University of Toronto
Project: Novel mechanisms of cell death and organelle stress in placental pathologies

Giovanni Tossetta, PhD, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche
Project: Role of VHL in placental mesenchymal stem cells guidance in normal and pathological conditions

PRESENT COLLABORATIONS

Within the Department of Physiology:

Martin Post
Alan Bocking
S. Lee  Adamson (Cross-appointed)

Outside the Department of Physiology:

University of Toronto

Andrea Jurisicova, Department of Obstetrics & Gynaecology (LTRI)
Ori Nevo, Department of Obstetrics & Gynaecology (Sunnybrook Health Centre)
John Kingdom,  Department of Obstetrics & Gynaecology (MSH)
Igor Jurisica, Department of Computer Science and Medical Biophysics (UHN)
Stephen Scherer, Department of Medicine (SickKids)
Michelle Letarte,  Departments of Immunology, Medical Biophysics, Obstetrics/Gynaecology and Paediatrics (SickKids)
Sue Varmuza, Department of Zoology  (UofT)
Rosanne Weksberg, Department of Molecular and Medical Genetics and Paediatrics (SickKids)
Chun Peng, York University
Daniel MacPhee, University of St John, Newfoundland
Anne Croy, Queen’s University, Kingston

International:

Tullia Todros, Roberta Cavalli, Caterina Guiot, University of Torino, Italy
Luana Paulesu, Felice Petraglia, University of Siena, Italy
Stacy Zamudio, Nick Illsley, Hackensack University Medical Center, New Jersey, USA
Vicki Clifton, University of Adelaide, Australia
Ariel Many, Department of Obstetrics and Gynecology, Tel Aviv, Israel
John Challis, Perth, Australia and Professor Emeritus, University of Toronto, Departments of Physiology, Medicine and Obstetrics & Gynaecology

Recent Publications

1. CANIGGIA, S.Grisaru-Gravnosky, M. Kuliszewsky, M. Post, S.J.Lye. Inhibition of TGFß3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J. Clin. Invest. (1999) 103:1641-1650. Role: Principal Author.

2. CANIGGIA, H. Mostachfi, J. Winter, M. Gassmann, S.J. Lye, M. Kuliszewski, and M. Post. Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation via TGFß3. J. Clin. Invest (2000) 105: 577-587. Role: Principal Author.

3. Soleymanlou N., Y. Wu, X. Wang, A. Jurisicova, M. Post, and I. CANIGGIA. A novel pro-apoptotic splice isoform of Mtd and its role in the pathogenesis of preeclampsia. Cell Death Differ. (2005) 12: 441-452. Role: Senior responsible author.

4. Soleymanlou N., Y. Wu, X. Wang, A. Jurisicova, M. Post, and I. CANIGGIA. A novel pro-apoptotic splice isoform of Mtd and its role in the pathogenesis of preeclampsia. Cell Death Differ. (2005) 12: 441-452. Role: Senior responsible author.

5. Yinon, Y., Nevo, O., Xu, J., Many, A., Rolfo, A., Todros, T., Post, M., CANIGGIA. I. Severe IUGR pregnancies have increased placental endoglin levels: hypoxic regulation via TGFβ3. Am. J. Pathol. 172(1):77-85, 2008. Role: Senior Responsible Author.

6. Nevo, O., Many, A., Xu, J., Kingdom, J., Piccoli, E., Zamudio, S., Post, M., Bocking, A., Todros, T., CANIGGIA, I. Placental expression of sFlt-1 is increased in singletons and twin pregnancies with intrauterine growth restriction. J Clin. Endocrin. Metabol. 93(1):285-92, 2008. Role: Senior Responsible Author.

7. Ray, J.E, Garcia, J., Jurisicova, A., CANIGGIA, I. Mtd takes a swing: Pro-apoptotic Mtd/Bok regulates trophoblast proliferation in human placental development and preeclampsia. Cell Death Diff. 2010 May;17(5):846-59. Epub 2009 Nov 27. Role: Senior Responsible Author.

8. Rolfo, A., Many A., Racano, A., Tal, R., Tagliaferro, A., Ietta F., Wang, J., Post, M., and I. CANIGGIA. 2010. Abnormalities in Oxygen Sensing Define Early and Late Onset Preeclampsia as Distinct Pathologies. PLoS ONE 2010 Oct 12;5(10):e13288 Role: Senior Responsible Author.

9. T. Sivasubramaniyam, J. Garcia, T. Todros, I. CANIGGIA. Where Polarity Meets Fusion: Role of par6 in Trophoblast differentiation during placenta development and preeclampsia. Endocrinology. 2013 Mar;154(3):1296-309. doi: 10.1210/en.2012-1823. Epub 2013 Jan 22.

10. Sarah Chauvin, Yoav Yinon, Jing Xu, Leonardo Ermini, Julien Sallais, Andrea Tagliaferro, Tullia Todros, Martin Post, I. CANIGGIA. Aberrant TGFβSignalling Contributes to Dysregulation of Sphingolipid Metabolism in Intrauterine Growth Restriction. J Clin Endocrinol Metab. 2015 May 5:jc20151288. [Epub ahead of print]  Role: Senior Responsible Author

Appointments

Obstetrics & Gynecology, Physiology, Institute of Medical Sciences

Courses

Course Number: PSL470H - Developmental Cardiovascular Physiology; PSL421H - Reproduction II: Pregnancy and Birth; PSL1067 - Current Advances and Techniques in Developmental Physiology; PSL1022H - Reproductive and Developmental Medicine
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