An NCI-designated Comprehensive Cancer Center
By Abe Rosenberg | November 1, 2019
City of Hope Rising Stars
Sangeeta Dhawan, Ph.D., Dustin Schones, Ph.D., Zhen Chen, Ph.D.
They come from Amritsar, India; Beijing, China; Circle Pines, Minnesota … and lots of places in between. They are the next generation of diabetes researchers at City of Hope, bringing their diverse backgrounds, fresh perspectives, and youthful drive and enthusiasm to our mission to eliminate type 1 diabetes once and for all.

Sangeeta Dhawan, Ph.D.: “What Goes Wrong?”

What do silkworms and fruit flies have to do with diabetes?  
 
Plenty, it turns out, if you’re a young researcher with an intense curiosity plus a desire to benefit the world.
 
From her earliest days in India, Sangeeta Dhawan, Ph.D., wondered about the way cells behaved. The child of two doctors, her home environment fueled her inquisitiveness. “Mom and Dad would always be teaching me about science,” she recalled.
 
As she studied those intriguing insects during her doctoral program, Dhawan realized two things.
 
“I discovered that molecular pathways tend to be common among different organisms,” she said. “And I knew that I wanted to work with cells in a way that would help people.”
 
She found her own pathway in the study of diabetes and the mechanics of insulin-producing beta cells.
 
“Beta cells are the center of our health and well-being,” she said. “It’s an exciting field.”
 
Most exciting is her search for the “switch”: unique mechanisms that control beta cell reproduction, as well as when they begin making insulin — and why, sometimes, they stop.
 
In other words, she asks, “What goes wrong?”
 
Immediately after birth, “beta cells duplicate very rapidly,” she explained, “but at this stage, they don’t know how to function. They cannot sense the changes in blood sugar levels.
 
“Adult beta cells, on the other hand, know how to function, but they duplicate very slowly. Why?”
 
Understanding this delicate balance is key, Dhawan said, to developing more efficient ways to rapidly grow functioning beta cells for transplant, as well as to possibly reactivate a diabetic’s remaining beta cells that have gone dormant. Her work focuses on the gene regulation that guides this balance.
 
At City of Hope since 2017, Dhawan delights in contributing to its fast-growing diabetes research center and working alongside internationally renowned researchers like Dr. Arthur Riggs, Ph.D., whose pioneering work inspired her to study the underpinnings of gene regulation.
 
“The long history of breakthroughs in diabetes research at City of Hope is like a beacon to me,” she said.

Zhen Chen, Ph.D.: In the Family

Zhen Chen, Ph.D., didn’t have to look very far for motivation when it came to working at City of Hope.
 
“I prepared for years!” she said.
 
Raised in China, she began studying English in third grade. She made friends with visiting American scientists she met at college, and worked with one from Riverside, California, when he set up a lab in Beijing.
 
Then, of course, there’s the family element.
 
“My mom has type 2 diabetes,” she explained. “And she had breast cancer.”
 
Chen remembers a difficult two-week period during graduate school when she juggled her teaching and research while accompanying her mother to daily postsurgery radiation treatments “in a quiet basement” of a Beijing hospital.
 
That experience, plus watching her mother deal with diabetes years later, “made me more aware” of how important her own research could be.
 
She joined City of Hope in 2016, where she focuses on the damage wreaked by diabetes on the body’s vascular system.
 
“It’s what people suffer [from] the most,” she pointed out.
 
Diabetics may face a variety of vascular problems ranging from peripheral artery disease to neuropathy (loss of sensation in the feet) to strokes. Chen searches for strategies to protect the blood vessels while also investigating ways to reverse damage already done.
 
She believes the damage may begin with the body’s endothelial cells — a thin layer of simple cells that line the blood vessels throughout the circulatory system. They perform many functions, from filtering impurities to preventing blood clots and inhibiting inflammation. Too much glucose may impair these cells from doing those critical jobs.
 
Working with a grant from the Chan Zuckerberg Initiative, Chen is applying leading-edge computational tools to map the inner workings of endothelial cells.
 
To better understand how and why diabetes begins, Chen is also taking a close look at noncoding RNA, or RNA molecules transcribed from DNA that do not express proteins.
 
“For over 100 years, we’ve focused on genes that express proteins,” Chen explained. “But 98% of our genes don’t, and very little is known about them.” What is known is that noncoding RNAs perform a variety of regulatory functions in the body. Chen believes there are important clues to be discovered there.
 
“We should target the noncoding region,” she declared. “It may contain the answers.”

Dustin Schones, Ph.D.: “I Like Solving Puzzles.”

Somewhere buried among the mementos in the Schones family home in Minnesota, there’s an old picture of 5-year-old Dustin Schones in his kindergarten class. He’s wearing a lab coat.
 
“I’ve wanted to be a scientist ever since I was old enough to walk and talk,” he declared.
 
He’s driven by a love for science implanted at an early age. “I come from a family of educators, so a career in scientific research is not too far off the path,” he said.
 
His path at City of Hope involves the study of obesity and how it contributes to several long-term diseases, including diabetes. Schones’s lab is examining how external forces like diet and environment  alter a person’s chromatin — the all-important “packaging” that compresses our DNA inside each and every cell and also controls which parts are turned “on” or “off” properly. Some of those changes may persist even after the patient loses weight.
 
Within that investigation, Schones and his team are going where few have gone before: He’s discovered that nearly half of the changes to chromatin take place at “transposable elements” (TEs), also known as “jumping genes” because these DNA sequences move from one part of the genome to another.
 
“Our work represents the first attempt to assess the consequences of TE dysregulation in obesity and how this contributes to long-term disease risk,” he said.
 
Ask him why this work fascinates him, and his answer is simple:
 
“I like solving puzzles!”
 
And why City of Hope?
 
“It’s so unlike a university setting,” he said. “Being near patients has totally changed the way I think about my work. Now I think much more about how my research may one day solve clinical problems. The translational component is very important to me.
 
“And that’s the cool thing about City of Hope. Even if our lab doesn’t solve a specific problem, there are so many opportunities to share our research with others here who just may do it.”
 
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