Clifford Librach

Degrees: MD

Affiliations: Create Fertility Centre,
Women’s College Hospital,
Sunnybrook Health Sciences Centre and Research Institute

Research Synopsis

Keywords: Andrology, animal models, angiogenesis, assisted reproductive technology, brain, cardiac muscle, cell biology, central nervous system (CNS), cardiac repair, development, epigenetics, folliculogenesis, infertility, growth factors, HLA-G, immunology, mesenchymal stromal cells, microvesicles, molecular biology, neuronal cell culture, ovarian biology, oxidative stress, perivascular cells, pre-clinical research, preeclampsia, regenerative medicine, reproductive biology, spermatogenesis, spinal cord injury, stem cell biology, telomere, traumatic brain injury, umbilical cord perivascular cells

Detailed Description: Our lab focuses on five exciting and unique areas of research, including human embryology, andrology, ovarian biology, perinatal biology, and stem cell biology:

1) Investigation of factors regulating human oocyte and embryo quality in assisted reproductive techniques (ART)

• Study of maternal and paternal contributions to early embryo development;
• Study of mechanisms of oocyte maturation and activation;
• Development of assays to increase and assess embryo quality for successful implantation;
• New advancements in cryopreservation of human oocytes and embryos.
• Advancement of next generation sequencing for clinical practices

2) Evaluation of genetic causes of male infertility and of paternal contribution to fertilization and embryo development

• study of oocyte-activation factors in sperm and their role in male infertility;
• study of chromosome physiology in sperm (including spatial localization and packaging, DNA damage/fragmentation, telomere length, and aneuploidy) and its role in male infertility.
• Study of specific populations of microparticles and exosomes, and their contents, and their effects on male fertility

3) Investigation of molecular mechanisms regulating normal ovarian biology and Polycystic Ovarian Syndrome (PCOS) to identify novel biomarkers for clinical use

• proteomic evaluation of follicular fluid and serum biomarkers in PCOS;
• identification of genes regulating follicular cells and their role in PCOS.
• Characterization of exosomes and small RNA content from follicular fluid and their contribution to PCOS.

4) Prospective identification of women who are at risk for preeclampsia during pregnancy

• study of the role of the immunoprivileged molecule HLA-G in the etiology of preeclampsia.
• Identification of exosomes found in the serum, and their use as novel biomarkers of preeclampsia.

5) Pre-clinical investigations of human umbilical cord-derived stem cells for regenerative medicine applications
• Characterization of the stem cell, growth, and molecular properties of human umbilical cord-derived perivascular cells (HUC-PVCs);
• In vitro differentiation and tissue injury modeling;
• In vitro co-culture assays to support the maintenance and growth of stem cell populations;
• In vivo differentiation, contribution to regeneration, and homing assays in rodent and porcine models of disease and injury, including but not limited to myocardial infarction, spinal cord and traumatic brain injury, toxicant induced liver and testis injury.

METHODS USED

Cell and tissue culture:  Cardiomyocytes, endothelial cells, neurons, first trimester and term human umbilical cord-derived perivascular cells (HUC-PVCs), HUVEC, bone marrow-MSCs,  rat cardiomyocytes, rodent cortical and SCG neuronal culture, spermatogonial stem cell, mouse embryonic fibroblasts, NTERA2 cells,  human granulosa cells isolation and culture

Procedures: Elisa, gene expression analysis, immunohistochemistry, immunocytochemistry, intracellular injection, isolated vellsel preparation, mass spectrometry, micro and macro stimulation of peripheral nerves and central brain structures, microarrays, proteomics, qRT-PCR, RT-PCR, signal transduction characterization, western blot, perivascular cell isolation, telomere length assays, sperm DNA decondensation, sperm protein isolation, red blood cell depletion

EQUIPMENT USED

Analytical balances, benchtop centrifuge, blotting apparatus, culture hood, culture incubators, deconvolution fluorescence microscope, dissecting microscope, fluorescence microscope, gel apparatus, low- and high-speed centrifuge, low and ultralow freezers, microwave oven, mini vortexer, plate reader, real-time/thermocycler, stirrer/hot plate, water baths.

PRESENT TRAINEES

Farwah Iqbal
Pamela Chan
Peter Szaraz
Katya Park
Parshvi Vyas

PRESENT COLLABORATIONS

Outside the Department of Physiology:
Claude Robert,  University of Laval
Ori Nevo,   Sunnybrook Health Sciences Centre
Kirk Lo, Department of Urology, Mount Sinai Hospital
Andrew Baker, Departments of Anesthesia and Surgery, University of Toronto, Canada
Michael Fehlings, Division of Neurosurgery, University of Toronto, Canada
Li Ren-Ke, Department of Surgery, University of Toronto, Canada
Richard Oko, Faculty of Health Sciences, Queen's University, Canada
Benjamin Tsang, Department of Obstetrics and Gynaecology, University of Ottawa, Canada
Sarah Kimmons, Department of Animal Sciences, McGill University, Canada

Committee member/Officer of national or international scientific organization:
IVF improvement Committee, Canadian Fertility and Andrology Society
Better Outcomes Registry and Network (BORN)
Canadian Assisted Reproductive Technology Registry

Recent Publications

Dar S, Lazer T, Swanson S, Silverman J, Wasser C, Moskovtsev S, Sojecki A, and Librach CL. Assisted reproduction involving Gestational Surrogacy: an analysis of the medical, psychosocial and legal issues. Experience from a large surrogacy program. Human Reproduction Update. 2014 Nov 25;30(2):345-352. Senior Responsible Author.

Kuznyetsov V, Moskovtsev S, Crowe M, Lulat A, Librach CL. Vitrification of a small number of spermatozoa in normozoospermic and severely oligozoospermic samples. Systems Biology in Reproductive Medicine. 2014 Nov 21;61(1):13-17. Senior Responsible Author.

Quach K, Grover S, Kenigsberg S, Librach C. A Combination of Single Nucleotide Polymorphisms in the 3’Untranslated Region of HLA-G is Associated with Preeclampsia. Human Immunology. 2014 Oct 9;75(12):1163-70. Senior Responsible Author.

Aarabi M, Balakier H, Bashar S, Moskovtsev S, Sutovsky P, Librach C, Oko R. Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice. FASEB. 2014 Oct 3;28(10):4434-4440. Co-Principal Author.

Lazer T, Dar S, Shlush E, Al Kudmani B, Quach K, Sharma P, Baratz A, Glass K, Librach C. Analyzing IVF outcome after a minimal stimulation protocol compared to a high dose antagonist protocol for low responders. European Journal of Obstetrics and Gynecology. 2014 Feb. In Press. Senior Responsible Author.

Hong SH, Maghen L, Kenigsberg S, Teichert A, Rameloo A, Shlush K, Szaraz P, Pereira S, Lulat A, Xiao R, Yie S, Gauthier-Fisher A, Librach C. Ontogeny of Human Umbilical Cord Perivascular Cells: Molecular and Fate Potential Changes During Gestation. Stem Cells and Development. 2013 Sep 1;22(17):2425-2439. Senior Responsible Author.

Grover S, Shmorgun Z, Moskovtsev SI, Baratz A, Librach CL. Assisted reproduction in a cohort of same-sex male couples and single men. Reproductive Biomedicine Online. 2013 Aug 1;27(2):217-221. Senior Responsible Author.

Behrouzi B, Kenigsberg S, Alladin N, Swanson S, Zicherman J, Hong SH, Moskovtsev SI, Librach CL. Evaluation of potential protein biomarkers in patients with high sperm DNA damage. Systems Biology in Reproductive Medicine (2013).

Dar S, Grover SA, Moskovtsev SI, Swanson S, Baratz A, Librach CL.In vitro fertilization-intracytoplasmic sperm injection outcome in patients with a markedly high DNA fragmentation index (>50%). Fertility and Sterility (2013).

Hong SH, Maghen L, Kenigsbcerg S, Teichert AM, Rammeloo AW, Shlush E, Szaraz P, Pereira S, Lulat A, Xiao R, Yie SM, Gauthier-Fisher A, Librach CL.Ontogeny of Human Umbilical Cord Perivascular Cells: Molecular and Fate Potential Changes During Gestation. Stem Cells and Development (2013).

Alladin N, Moskovtsev SI, Russell H, Kenigsberg S, Lulat AG, Librach CL.The three-dimensional image analysis of the chromocenter in motile and immotile human sperm. Systems Biology in Reproductive Medicine (2013).

Moskovtsev SI, Librach CL. Methods of sperm vitality assessment.Methods in Molecular Biology (2013).

Balakier H, Xiao R, Zhao J, Zaver S, Dziak E, Szczepanska K, Opas M, Yie S, Librach C. Expression of survivin in human oocytes and preimplantation embryos. Fertility and Sterility (2013).

Balakier H, Sojecki A, Motamedi G, Bashar S, Mandel R, Librach C. Is the zona pellucida thickness of human embryos influenced by women's age and hormonal levels? Fertility and Sterility (2012).

Yie SM, Li LH, Xiao R, Librach CL. A single base-pair mutation in the 3'-untranslated region of HLA-G mRNA is associated with pre-eclampsia. Molecular Human Reproduction (2008).

Sheshgiri R, Rao V, Tumiati LC, Xiao R, Prodger JL, Badiwala M, Librach C, Delgado DH. Progesterone induces human leukocyte antigen-g expression in vascular endothelial and smooth muscle cells. Circulation (2008).

Appointments

Primary: Obstetrics and Gynecology
Cross Appointment: Institute of Medical Sciences