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 three primary areas of research are 1. Male infertility where he is supported by numerous national and international medical granting agencies investigating the mechanisms leading to severely impaired sperm production 2. Peyronies disease mechanisms and novel therapeutic drug discovery 3. Men’s Health Promotion, behavioral change and community involvement in partnership with the Canadian Men’s Health Foundation.

To date, Dr. Flannigan has published over 100 articles, abstractions 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

Composite Health Behaviour Classifier as the Basis for Targeted Interventions and Global Comparisons in Men’s Health

Our group created a classification system to evaluate important health behaviours of Canadian men. We identified that over 40% of Canadian men demonstrate 3/5 unhealthy behaviours and a significant need exists to help men live healthier lives and prevent future lifestyle-related medical conditions.

Unhealthy Behaviors Among Canadian Men are Predictors of Comorbidities: Implications for Clinical Practice

This study evaluated 2000 Canadian men. We identified men with unhealthy lifestyle choices demonstrated increased rates of medical conditions. Interestingly, unhealthy sleep patterns were associated with erectile dysfunction and depression.

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.

Changes in Practice Patterns in Male Infertility Cases in the United States: The Trend Toward Subspecialization

The field of subspecialty male infertility experts is expanding with recently trained Urologists. More procedures addressing treatment of infertility are being performed such as varicocele repairs, and are being performed by sub specialists rather than generalists.

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.

Perineal Ultrasound: A Review in the Context of Ejaculatory Dysfunction

Evaluation of men with ejaculatory dysfunction can be challenging. We discuss potential future directions using transperineal or transrectal evaluation of ejaculatory function in men.

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).