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College of Medicine Alumni Magazine - Fall 2015 Puzzle Master: Divya Sagar, PhD, '15

Divya Sagar received the Amedeo Bondi, PhD, Award for excellence in research performance. Its namesake was sculpted in bas-relief by Mark Victor.

Divya Sagar received the Amedeo Bondi, PhD, Award for excellence in research performance. Its namesake was sculpted in bas-relief by Mark Victor.

Using the metaphor of a puzzle, neuroscientist Divya Sagar, PhD '15, observes that researchers like herself have "all these pieces" of information about the brain. "It's just a matter of connecting the dots and putting them in the right place." Fortunately, Dr. Sagar has become an adept puzzle-solver when it comes to the human brain. Sagar, who received her doctoral degree in neuroscience from the College of Medicine's Graduate School of Biomedical Sciences and Professional Studies, also has a keen interest in immunology. For her doctoral thesis, she focused on multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis.

Because MS patients experience a wide variety of potentially debilitating problems, such as blurred vision, difficulty with balance and coordination, overall weakness, and pain, "the quality of life for these patients really is not good," Sagar says.

"While many MS treatments are on the market, they are not specific to any particular cell type or any particular function," she notes. These "non-specificity issues" can cause additional problems on top of the MS. Patients may develop incurable secondary brain lesions, for example, as a result of general immune suppression. In the laboratory of her mentor, Professor Pooja Jain, PhD, Sagar focused on dendritic cells, key regulators of the immune system, a long-term research area in Dr. Jain's laboratory. She used animal models of MS to study how these migrate into the brain and spinal cord.

Finding a missing piece

At the conclusion of her thesis, she says, "I successfully identified a particular target known as CLEC12A, a lectin highly enriched on dendritic and other myeloid cells." Targeting these cells, Sagar and her colleagues blocked this lectin receptor. They then found that the disease symptoms exhibited by the animals dropped significantly. Since MS can present as either progressive or relapse (episodic), Jain's lab tested their theory in each type of animal model. In both scenarios, targeting CLEC12A lessened the disease's symptoms and attenuated relapses.

Sagar had identified a missing piece. The treatment she and Jain's lab developed "specifically targets the cells that initiate inflammation after migrating into the brain," she says. "We believe we should let the rest of the immune cells come and go as they like and perform their function." This precision should reduce the secondary problems associated with current, generalized treatments.

While Sagar acknowledges that their treatment needs further testing and evaluation, she believes it has very good promise as a clinical trial candidate.

"The process of being creative, yet scientifically sound, is very attractive to me," Sagar says. She will continue this creative inquiry for her postdoctoral work at MedImmune, a research and development arm of AstraZeneca, where she previously interned. At MedImmune, she will have the opportunity to research neurological illnesses.

"It seems like [the position] was tailor-made, because I will continue studying the role of dendritic cells in autoimmunity, particularly that of plasmacytoid dendritic cells," she explains. Though Sagar will focus on multiple sclerosis and lupus, she will have opportunities to research other illnesses as well.

The Legacy of Amedeo Bondi, PhD

A renowned microbiologist and educator, the late Amedeo (Mede) Bondi, PhD, professor emeritus, came to Hahnemann Medical College in 1947 as the first chair of the Department of Microbiology. In 1972 he became the first dean of the Graduate School at Hahnemann University, continuing to teach graduate students, medical students and allied health professional students. Bondi’s pioneering research related to antimicrobic resistance mechanisms led to his development of the commonly used antibiotic disc sensitivity test. He also discovered the production of penicillinase by bacteria, laying the foundation for penicillinase-resistant penicillins, and contributed to improved vaccines for typhoid, brucellosis and whooping cough. In 1990, colleagues, past students and friends created an endowment in honor of Bondi to provide annual awards to graduate students: the Bondi Fellowship Award to a continuing graduate student and the Bondi Award to a graduating PhD. Although Amedeo Bondi passed away in 2005 at the age of 92, his spirit of inquiry, like his legacy, lives on.

On the path to discovery

Originally from Mumbai, India, Sagar came to the United States for college at Rutgers University, New Brunswick. The change was difficult at first. "There are a lot of differences in the way you learn and the way knowledge is imparted to you," she observes. "Ultimately, however, it was a good transition. I think I managed to ease into it pretty successfully!"

A double major in biology/neuroscience and psychology at Rutgers, Sagar had early opportunities to conduct research. After graduation, she began the Rutgers master's program in biological sciences. It was during this time that she interned at MedImmune. Her job there studying respiratory illness in children was her first real exposure to the field of immunology.

After the internship, Sagar returned to her coursework and lab, where she did research with an immunologist who was studying the role of glial cells in neuroinflammatory disease. "That's how my interest in interdisciplinary research in neuroscience and immunology really began," Sagar notes.

Sagar decided she wanted to pursue her doctorate. During her internship at MedImmune, she noted that Drexel students enjoyed a great reputation throughout the company. As she considered PhD programs, Drexel emerged as a strong candidate.

At the College of Medicine, Sagar found a lab and a PI that closely mirrored her own interests. "When I came in, I specifically wanted to study the relationship between the immune system and the brain," she says. Jain is highly regarded in this field. Sagar praises Jain as an outstanding mentor who has greatly influenced her as a young scientist, and whose lab was a stimulating and collaborative work environment.

Considering Sagar's career trajectory and scientific discoveries, it is clear she sees individual pieces and knows how to contextualize them. Now entering her postdoc, she will continue to search for new clues. "The brain is such a mystery," Sagar says. "I think we've only now begun to unravel its workings. Hopefully, we will do much more in the next decade or so — I think we're close. We just have to link all the pieces of information we as scientists discover and study to put everything together."

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