From murky beginnings, a clear view of the future

Many forks in the road led to PhD graduate Darpan Malhotra's groundbreaking corneal research

Sasha Roeder Mah - 3 December 2019

"Surreal," said Darpan Malhotra, when asked how it feels to have completed his PhD. "Just over five years ago, I thought I would never get here," he added.

Malhotra, PhD '19, has been working in the lab of biochemistry professor Joe Casey since September 2013, when he arrived in Edmonton from Delhi, India. Welcomed at the Edmonton International Airport by his new supervisor, he was struck by the vast, open landscape. "Where are all the buildings? Where are the people?" he wondered, Delhi's 22-million-strong population and concrete jungle still fresh in his mind as they cruised to a halt on the campus that would be his new home. "It's so peaceful," he remembers thinking.


His path here was anything but.


False starts


Following a master's in biotechnology from India's Amity University, Malhotra completed a dissertation scholarship and a year as a junior research fellow with the Indian Institute of Technology Bombay. Building on that momentum, he applied and was accepted into the National University of Singapore biomedical program, and immediately began preparing for the move. Three days before his planned departure, he was told funding had run out. Singapore was no longer an option. Shaking off that disappointment, he was in short order accepted to the Hanover Medical School in Germany. Once again, Malhotra got his visa, packed up his life, but a week before he was to leave home, he was advised that funding had run out and there was no future for him there.


"Fun fact," said Malhotra ruefully, when asked how he ended up at the University of Alberta. Following those two near misses, "I got rejected over 100 times" from programs and labs all over the world. He laughs about it now, but that year of uncertainty was a stressful one.

A new beginning


Eventually, Malhotra came across the unique work being done by Casey in the role of membrane transport in corneal diseases. "My focus was to find an area that isn't as known or popular, where I could make a contribution," said Malhotra. "I also knew I wanted to work in a lab where I'd have good support around me." That would come not only from Casey, he knew-who wasted no time bringing him on board once he saw his CV-but also from the Membrane Protein Disease Research Group and the International Research and Training Group (IRTG) in Membrane Biology, whose diverse memberships would provide rich opportunities for collaboration, access to international experts and a deeply supportive environment.


Malhotra's work is in the area of corneal dystrophies, diseases of the outermost layer of the eye. In these genetic diseases, there is a fluid imbalance in the cornea, along with other pathophysiological changes that lead to progressive vision loss. Patients experience an unexplained loss of endothelial cells from the cornea's innermost layer.


In professor Casey's lab, Malhotra has focused on the corneal endothelial transport protein SLC4A11, which functions to move fluid across the plasma membrane, he explains. In certain corneal diseases, SLC4A11 is mutated, and Malhotra wanted to figure out whether these mutations cause a loss of endothelial cells in patients. He discovered that the large ribbon-like extracellular loop of SLC4A11, previously with no known function, serves as an adhesion site for cells. Mutations in the loop contribute to compromised endothelial cell adhesion. Ultimately, the loss of these healthy cells leads to loss of vision.


SLC4A11 research has been highly rewarding for Malhotra. In 2015, he won the prestigious Canadian Vanier Scholarship, which totalled $150,000 over three years. He spent the following summer working in the lab of Richard Zimmermann at Saarland University in Homburg, Germany, made possible through a scholarship from the IRTG. Then, after delivering a presentation on his work on cell adhesion in Hawaii to the Association for Research in Vision and Ophthalmology (ARVO) in 2018, Malhotra connected with Jodhbir Mehta, a researcher from Singapore who offered up valuable space in his lab to fill in the missing pieces of his research. For two months in Singapore, he got to test his research in a system closer to humans, using endothelial cells from donor human corneas. This valuable experience validated his previous findings.


"People work differently in Canada, the States, India, Germany," Malhotra said. "To have the opportunity to work in another lab, get their help and expertise, all while enjoying a different cultural environment, was amazing for me."


Future focus


What's next for Malhotra? He will put in two years as a postdoctoral researcher on this project, which is now moving into the area of therapeutics for endothelial corneal diseases. He also looks forward to pursuing his other passion: business.


"I can get into pharmaceutical companies and work with them as a scientist, while also providing business support," he mused. "There's also life-science consulting, where there's a demand for PhDs who also understand a bit of business." Malhotra already works in this role with U.S.-based firm PreScouter, and sees a wealth of opportunities in the industry.


Branching out beyond academia is about new challenges. But the opportunity to supplement his income is also a reflection of his most powerful motivation-to give back to his parents, who sacrificed much to support his academic journey, and to pass on his good fortune to his sister, who hopes to pursue graduate studies of her own in fashion in New York City.


"I want to pay for her tuition as I promised her I would," he said. "That is important to me; I'm a family guy."


Malhotra's PhD survival tips


  • Do your research before you start. Will there be a viable career waiting for you when you're finished? Consider options beyond a future in academia.


  • Be honest with your supervisors about your goals. This will help them assist you in planning your future.


  • Apply for awards. The Faculty of Graduate Studies and Research offers workshops, seminars and one-on-one assistance to guide you through the process. Take a chance; if you don't apply, you'll never win.


  • Take care of yourself. "Work-life balance is crucial," said Malhotra. Take time for hobbies. Spend time with friends. "Dancing was a huge outlet for me. I got involved in a tango group called Casa Tango. I did a lot of running, and I started reading fiction. Next on my reading list is The Handmaid's Tale."