Exceptional Thesis Award 2018

By Charu Mehta, CMB graduate student

Grit and resilience are the most paramount traits for graduate students pursuing a PhD, especially in Biology where experiments can often be time-consuming and unpredictable. Among the many students and scientists I have come across, no one emulates grit and resilience better than Diya Binoy Joseph. When I asked her what her working philosophy was, her answer was simple and striking: “You will have days when everything fails. If you work enough days, things will turn around.” A brilliant motto I have now printed out as a reminder on my desk.

Wolffian duct cells
Wolffian duct cells (shown in pink) move into the urethra and bladder epithelium (shown in green) of Dnmt1 mutant mouse embryos

I was elated to find out that she had won the 2018 CMB Exceptional Thesis Award, and immediately wrote to congratulate her. Humble and gracious as ever, she confers much gratitude to her thesis advisor, Dr. Chad Vezina, and the CMB program. The award has motivated her to continue working hard, she adds.

The CMB Exceptional Thesis Award is given every year in recognition of the distinguished work contributed by a student during the completion and defense of their thesis. In honor of her thesis, “The role of DNA methylation in lower urinary tract development and prostate homeostasis,” Diya has received a plaque, $250, and her name on a plaque in the Bock Penthouse.

Diya completed her school and bachelor’s degree in India. She was always drawn to science as a child and her heart was set on studying Biology after high school. In a competitive exam written by more than a million high school graduates in India, she secured herself an admit to a premier institution, the National Institute of Technology, Calicut, where she majored in Biotechnology. Not only did she perform well, she developed great relationships with her professors who encouraged her to pursue a PhD, not a common feat if you are a woman in India. As an undergraduate, Diya was selected to the Khorana Scholars program, a prestigious and highly selective summer research program, one of the very few available to Indian students that gives them a chance to visit world-class laboratories in the US. Her visit to the University of Michigan, Ann Arbor further cemented her interest in biological research and she decided to apply for PhD programs in the US.

In the Vezina lab, Diya worked on the role of the epigenetic modification DNA methylation on the development of the male lower urinary tract. The lower urinary tract in the male also comprises the prostate which is very susceptible to environmental agents including endocrine disrupting chemicals like Bisphenol A. To better understand the role of DNA methylation in the normal course of lower urinary tract development, she generated mouse models lacking the major DNA methylating enzyme, DNMT1, in the epithelium of the developing lower

Normal bladder epithelium (shown in green) has a protective barrier (shown in red) that protects the underlying tissue from exposure to the contents of urine. Dnmt1-deleted bladder epithelium is damaged and has a broken bladder barrier (indicated by white arrows). Wolffian duct cells replace the damaged bladder epithelium and restore a continuous bladder barrier.

urinary tract. DNMT1 deletion inhibited prostate bud formation through widespread DNA damage and apoptosis. Additionally, she noticed that bladders of these mice were also severely affected by DNMT1 deletion. The bladder epithelium was considerably thinner and appeared damaged compared to normal. Her keen observation and creativity led to the surprising discovery that epithelial cells from the Wolffian duct (precursor of the vas deferens and seminal vesicle) moved into the bladder to replace the damaged bladder lining and take on markers characteristic of the bladder. This was unexpected as the Wolffian duct epithelium is of a different germ layer origin than the epithelium of the bladder. Diya suggested this could have implications for bladder regeneration therapies. Her findings are noteworthy and were subsequently published in the high impact journal PNAS.

Dr. Vezina regards Diya as the architect of her own story. He emphasizes that it was Diya’s ingenuity and creativity that led her to discover the appearance of the new and unidentified cell type in the lower urinary tracts of conditional Dnmt1 mutant mice. Diya Binoy Joseph embodies the tenacity we expect in CMB graduate students and her resilience, enduring humility and amazing productivity will stand as a model for what current and future CMB trainees can accomplish if they work hard and believe in themselves, he adds.

Indeed, Diya’s story is one of resilience combined with positive attitude absolutely necessary for a scientist to thrive. When I asked her for some words of advice for younger scientists, she reaffirms, “Although working in the lab can at times be frustrating, a successful experiment can wipe out the disappointment of months of failed experiments.”

Outside of the lab, Diya likes to read, do origami, and crochet.

Read about past Exceptional Thesis Award recipients here.