Investigating how abnormal proteins lead to disease
Allysa Kemraj was in high school when doctors diagnosed her with a rare genetic disorder.
At Rutgers, she was surprised—and thrilled—to find a research lab that explores the science associated with her illness, Ehlers-Danlos Syndrome (EDS), a disease that affects the body’s connective tissue.
She soon began working in the lab.
“I was looking for research opportunities that would be a good fit,” says the senior from Roselle, New Jersey. “Then I found this lab, and I was completely floored.”
Kemraj is an undergraduate research assistant in a lab run by Jean Baum, a professor in the Department of Chemistry and Chemical Biology in the School of Arts and Sciences. Baum studies the interactions of proteins in the body and their role in Parkinson’s disease and other types of illnesses, including EDS, and a disease that affects patients receiving long-term dialysis treatment.
“Most people, understandably, don’t spend a lot of time thinking about the interactions between infinitesimal protein molecules in the body,” Baum says. “But when the interactions are disrupted or altered, serious illness can result.”
Baum’s lab uses sophisticated instruments to study proteins at the atomic level. And that helps break new ground on illnesses such as Parkinson’s disease, in which researchers have discovered proteins that fold abnormally and form long chains called fibrils.
Ehlers-Danlos Syndrome, meanwhile, refers to a group of disorders that include loose joints, stretchy skin, and excessive scar formation. These illnesses are linked to flawed collagen molecules, the most abundant protein in the body.
In high school, Kemraj noticed she was sustaining an inordinate number of injuries, such as dislocations and torn ligaments. “I played soccer and ran track,” she says. “I thought maybe it was growing pains.”
But then she began suffering from fainting spells and nausea. She and her family eventually went to the Mayo Clinic where doctors said she had EDS. Although she has a moderate form of the disease, Kemraj battles symptoms that include gastro-intestinal dysmotility, fatigue, and heart palpitations and arrhythmia. She makes frequent hospital visits. During her sophomore year at Rutgers, she sustained two ruptured discs in her back and required extensive medical attention and rehabilitation.
“I am lucky because when I go for medical care, I am able to leave the hospital and resume my life,” she says. “But that is not true for a lot of patients with EDS and other genetic disorders.”
Kemraj spends up to 20 hours a week in the Baum lab, working under Cody Hoop, a scientist who studies collagen illnesses like brittle bone disease. Hoop’s EDS research is supported by the American Heart Association because the disease in its most serious form can affect blood vessels and cause aortic aneurisms and ruptures.
For Kemraj, working so closely with her own illness is both an educational and edgy experience.
“I’ll be reading the medical literature and I’m, like, ‘Yup, that’s what’s going on in my body,’’’ she says. “It’s a little scary, but most of the time, it’s fascinating.”
Scientists studying proteins, a field known as structural biology, say their work offers hope for patients, particularly through drug discovery.
“If you know the shape of a protein and know the shape of a drug molecule that’s acting on that protein, you’ve got a good foundation from which to work to improve that drug,” says Andy Nieuwkoop, a professor in the chemistry and chemical biology department.
Both Baum and Nieuwkoop oversee research teams that use nuclear magnetic resonance (NMR) spectrometers—instruments that allow them to examine proteins at the atomic level. Protein samples are placed in a powerful magnetic field and bombarded with radio waves so that they send out distinct frequencies. Researchers use those signals to build models that show the location of each atom.
“They’re like MRIs, except for proteins rather than people,” says Nieuwkoop, whose team studies proteins and cell membranes, an emerging area that has implications for cancer and other diseases.
“The equipment we have at Rutgers is as good as anywhere in the world,” he says. “The technological advancements have gotten to the point where we can do experiments we could only dream about 10 years ago.”
The field attracts talented researchers, both graduate and undergraduate, who are drawn to the human health mission and eager to work with the NMR technology.
“I was drawn to the Baum lab because of its theme of protein-to-protein interaction,” says Hoop, a post-doctoral fellow who earned her Ph.D. at the University of Pittsburgh’s School of Medicine. “It’s important to understand how these interactions happen so that we can design drugs that can encourage or discourage interactions that may be connected to disease.”
Tamr Atieh, a chemistry major as a Rutgers undergraduate and now a graduate student, says the study of proteins is an increasingly influential field.
“A lot of the new drugs coming out are proteins,” he says.
Kemraj, meanwhile, said the Baum lab has had a major influence on her plans. She wants to go for an M.D./Ph.D. and devote her life to studying collagen and treating children.
“I want be a doctor and a specialist who can look my patients in the eye and say, ‘I, too, know what it’s like to have a chronic illness. And I’m going to do everything I can to help you.”’