Research
Research
Dr. Flannigan is a Principal Investigator at the University of British Columbia in the Department of Urologic Sciences. His research spans the full range of translation from basic science investigation of molecular and genetic mechanisms of male infertility and Peyronies disease, working towards novel therapeutic discovery and clinical trial investigation for medications, techniques and technologies being adopted to further clinical care.
His primary areas of infertility research are:
1. Investigating the molecular and genomic mechanisms of sperm production deficits.
2. Developing Artificial Intelligence-based technology to identify rare sperm and select the healthiest sperm for IVF-ICSI procedures.
3. Developing precision medicine based regenerative therapies for men with severe sperm production abnormalities (i.e. non-obstructive azoospermia) through integrating computational modelling and 3D bioprinting.
Dr. Flannigan’s research program is supported by numerous national and international medical granting agencies.
To date, Dr. Flannigan has published over 100 articles, abstracts and presentations. He has presented globally and has received numerous prestigious international awards for his research and contributions to the field. Since being recruited back to the University of British Columbia, he has secured several sources of funding for his research. Strengthening UBC’s research climate, he continues to hold an adjunct position at Weill Cornell Medicine to facilitate international research collaborations.
If you are interested in supporting our cause and donating to our research working to cure infertility and Sexual Dysfunction at the University of British Columbia, this can be performed through the VGH & UBC Hospital Foundation, the UBC Faculty of Medicine, and the Sullivan Urology Foundation. All are registered charities that issue tax receipts. Please visit our departmental research page for further information: https://www.prostatecentre.com/donate
Fertility Options After Vasectomy
In this review, we discuss in detail the various fertility options following vasectomy inclu
ding vasectomy reversals, sperm retrieval and IVF-ICSI. This serves as a great overview for anyone wanting more technical reading on the subject.
Automated rare sperm identification from low-magnification microscopy images of dissociated microsurgical testicular sperm extraction samples using deep learning
In this study, our collaborative research group developed an artificial intelligence-based algorithm to detect extremely rare sperm with 96% accuracy in semen samples and 85% accuracy in microTESE testis samples. We are working to clinically validate this tool in followup pilot trial.
Using clinically derived human tissue to 3-dimensionally bioprint personalized testicular tubules for in vitro culturing: first report
We are working to develop novel personalized medicine approaches to regenerating sperm production in the lab using techniques such as 3D Bio printing. Here we report the world’s first report using human testis cells.
The Kinetics of Sperm Return and Late Failure Following Vasovasostomy or Vasoepididymostomy: A Systematic Review
Our group evaluated all of the papers in the literature reporting on timing of sperm returning to the ejaculate following vasectomy reversals. We found that time from surgery to identification of sperm in the ejaculate was 1.7-4.3 months follow vasovasostomy, and 2.8 to 6.6 months following vasoepididymostomy. Late failures (disappearance of sperm) may occur in 0-12% of men after vasovasostomy and 1-50% after vasoepididymostomy, therefore consideration of sperm cryopreservation should be considered.
The Role of Lifestyle in Male Infertility: Diet, Physical Activity, and Body Habitus
We evaluated the literature pertaining to lifestyle and infertility. We identified evidence to suggest increased consumption of saturated fats, pesticide exposure, high intensity of exercise and extremes of body mass contribute to reduced male fertility; conversely, balanced dietary fat intake, moderation of physical activity and a healthy body mass index supported improved semen quality and birth outcomes.
Spermatogonial Stem Cell Transplantation and Male Infertility: Current Status and Future Directions
The field of spermatogonial transplantation and in vitro spermatogenesis are exciting areas of research in the field of male infertility and fertility preservation. We provide an overview of current research in the field as well as future directions that may serve to be promising clinical interventions and treatments.
Outcome of Oocyte Vitrification Combined with Microdissection Testicular Sperm Extraction and Aspiration for Assisted Reproduction in Men
With collaborators from Guangzhou China, we determined that fertilization rates, implantation rates and clinical pregnancy rates were comparable whether using fresh or vitrified oocytes, and through using sperm extracted by microTESE for men with poor sperm production, or, TESA for men with obstruction and normal sperm production.
Microdissection Testicular Sperm Extraction
Dr. Flannigan performs microTESE to identify and retrieve rare sperm from men with sperm production problems (non-obstructive azoospermia). In this article, he discusses the literature surrounding microTESE and clinical considerations.
Genetic Diagnostics of Male Infertility in Clinical Practice
Dr. Ryan Flannigan and Dr. Peter Schlegel discuss what is known in the literature surrounding genetics and male infertility.
45,X/46,XY Mixed Gonadal Dysgenesis: A Case of Successful Sperm Extraction
We discuss a report of successful sperm extraction in a man with a rare genetic diagnosis of 45X, 46XY Mixed Gonadal Dysgenesis. Thus, sperm retrieval may be consider in this cohort of men.
Attitudes Toward Penile Transplantation Among Urologists and Health Professionals
The field of penile transplantation is in its infancy. We performed a survey of Urologists and health care professionals to determine perceptions and attitudes toward this novel surgery. We identified the most common reservations and concerns were related to immunosuppression and potential subsequent effect on healthcare resource utilization.
Klinefelter Syndrome. The Effects of Early Androgen Therapy on Competence and Behavioral Phenotype
We performed a review of the literature discussing the role of early androgen supplementation in children with Klinefelter Syndrome on development. A summary of the literature suggests that early androgen supplementation combined with educational, family and social support may improve behavioural functioning.
Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes
Men with low testosterone may benefit from testosterone therapy; however, this can be contentious in men with prostate cancer given prostate cancer’s reliance on androgen receptor activation. Our study supports the hypothesis that testosterone therapy may be ontologically safe in men with low testosterone after definitive treatment or among men on active surveillance for prostate cancer.
Aberrant Y-Box RNA-Binding Protein Expression is a Candidate for Maturation Arrest Azoospermia
We identified a family of RNA-binding proteins and transcription factors that are dysregulated in men with severe male infertility. The associated pathways may be contributing to male infertility and are under further evaluation by our group in efforts to identify potential therapeutic targets.
Aberrant Y-Box Binding Protein Expression is a Candidate for Maturation Arrest Azoospermia
YBX2 is an RNA-binding protein and transcription factor that may be a culprit in men with maturation arrest severe male factor infertility (non-obstructive azoospermia). We determined that both RNA and protein levels appear to be significantly down regulated and may be inappropriately translated in germ cells. Our lab is continuing this research to further understand this abnormality and the mechanisms of male infertility.
Uncovering Biology of Klinefelter Syndrome (47,XXY) Infertility Using Novel 10x Genomics Single Cell Sequencing
Using multiple experimental tools, we determined that the majority of interstitial testis cells in men with Klinefelter Syndrome are in an immature state. We further identified a signal suggesting that both dilated and collapsed tubules may have rare spermatogonia present. Further work is being conducted to validate these results and identify mechanisms contributing to these findings.
Evaluating Transcriptional Regulation of Dilated and Collapsed Tubules Among Non-Obstructive Azoospermic Men Using 10x Single Cell Sequencing Platform
Using single cell RNA sequencing, we identified that cells from the testis of men with Klinefelter Syndrome demonstrate signals of cell death and injury. We identified a gene IGFBP5 that is over expressed in Klinefelter Syndrome and specifically among collapsed unhealthy tubules. This gene has been implicated in other fibrotic diseases in the body and is a candidate for future evaluation. Furthermore we identified signal suggesting immune cells may be singling cells in the testis to produce products leading to fibrosis.
3T Functional MRI Detects Differences in Neural Activation Among Men with Delayed Ejaculation & Orgasm
We sought to evaluate differences in neural processing among men with delayed orgasm and ejaculation when processing sexual stimuli. In this pilot study, we identified several regions of differential brain activation. This data serves as the rationale to further evaluate these differences with the aim to identify brain regions and neurotransmitters that may be amenable to pharmacologic treatment to help men with this condition.
Discrepancies Among Genomic & Histologic Phenotyping of Non- Obstructive Azoospermia
This research compared the gene expression profiles of testis tissue of men with different histologic subclasses of severe male infertility (non-obstructive azoospermia) and identified several differences in classification and the need for more precise biomarkers for classifying disease process.
MiRNA202-5p is Associated with Impaired Spermatogenesis, Not The Result of Impaired Spermatogenesis
Previous work by mentor Dr. Darius Paduch identified that microRNA-202-5p expression was significantly reduced in men with the most severe form of male infertilitySertoli Cell Only Syndrome (non-obstructive azoospermia). We used a murine model to determine that loss of germ cells does not result in decreased microRNA-202-5p expression, and thus, decreased levels in men with infertility may be a primary defect. Further work into the pathogenesis of microRNA-202-5p is underway to determine the potential mechanisms.
LARGE SCALE MIRNA AND PIRNA SEQUENCING ANALYSIS OF TESTIS BIOPSIES FROM FERTILE AND INFERTILE MEN REVEALS DIFFERENCES BETWEEN MIRNA AND PIRNA EXPRESSION DURING SPERMATOGENESIS CYCLE.
MicroRNAs and piRNAs are specific subtypes of small non-coding RNAs that are thought to play critical regulatory roles in sperm production. We compared the profiles of these small RNAs among men with normal spermatogenesis and different subtypes of non-obstructive azoospermia (severe male infertility).