Gastrointestinal problems are often the most difficult burden to bear for patients suffering from scleroderma, a chronic autoimmune disease that affects the body by hardening connective tissue.
Zsuzsanna McMahan treats these patients in her clinical work as a rheumatologist at the Johns Hopkins Scleroderma Center, and she can attest that their daily trials are heartbreaking.
“The entire length of the gut, from the esophagus to the rectum, can be involved,” she explains. “While some suffer from more minor issues, like acid reflux, others cope with terrible chronic diarrhea and fecal incontinence, which is just devastating and so socially isolating. Some patients just can’t tolerate food, so they can end up living on an IV.”
Among those with diffuse scleroderma who suffer from severe gastrointestinal issues, some 85 percent die within nine years.
McMahan is committed to easing their suffering. As a researcher in the Amos Food, Body and Mind Center, she is working with center co-director Pankaj “Jay” Pasricha and his team, as well as rheumatologists Livia Casciola-Rosen and Fredrick Wigley, to identify specific autoimmune response targets in the gut. “If we can better understand what cell types are targeted in the gut by the patient’s own immune response, we’ll gain knowledge of the pathogenesis of disease, which could help in developing novel treatments,” she says.
Launched in 2014 with the help of a generous gift provided by Mrs. Courtney Amos and Mr. Paul S. Amos, the Amos Center focuses on the gut-brain connection. It may be the only clinic in the United States that brings together gastrointestinal, rheumatology and psychiatric experts, who work together to treat patients in both physical and psychological distress, notes Pasricha, who is also director of the Center for Neurogastroenterology at Johns Hopkins.
“We’re using scleroderma studies as an initial step in better understanding the immune response in the gut. But we believe our findings could ultimately be applied to many other gastrointestinal illnesses.”
Scientists studying scleroderma have already identified antibodies in the blood that serve as biomarkers for different aspects of the illness, McMahan explains. There are known antibodies, for instance, that indicate patients are at increased risk of developing severe forms of skin thickening, vascular problems and interstitial lung disease.
“This suggests that there are also antibodies, or biomarkers, for gut problems in patients with scleroderma,” she says. “If we can identify those antibodies that target specific cells in the gut, we may gain insight into what exactly is causing the dysmotility – and be able to risk stratify patients and personalize treatments.”
The team’s lab studies focus on the nervous system of the gut, known as the enteric nervous system, which works together with the central nervous system to move food through the body.
Using a mouse model in the Pasricha lab, they remove the layer of gut that includes the nerve plexus and the smooth muscle around it (the layer responsible for motility), mash it up, then combine it with blood samples taken from patients with scleroderma to see if any antibodies from the patients’ blood bind with specific cells in the mouse gut. “Ultimately, we want to determine which proteins in the myenteric plexus are being targeted,” she says.
The knowledge gleaned could have far-reaching impact, McMahan notes. “We’re using scleroderma studies as an initial step in better understanding the immune response in the gut. But we believe our findings could ultimately be applied to many other gastrointestinal illnesses.”
For McMahan, whose clinical practice is devoted almost entirely to treating scleroderma patients with gut dysfunction, new knowledge – and treatments – can’t come soon enough.
“Many of my patients must cope with gastrointestinal problems they find humiliating – things that are not easily discussed, which leaves them socially isolated. It’s just horrible,” she says.
“Their experience is what motivates me and others on the team to push the science forward so that we can help bring relief.”
Don Willett May 7th, 2019
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How old are your cells? That’s the question at the heart of an intriguing line of aging research currently being led by Denis Wirtz, vice provost for research at The Johns Hopkins University, and geriatrician Jeremy Walston, the Raymond and Anna Lublin Professor of Geriatric Medicine and the Salisbury Family CIM Scholar.
The scientists’ team made headlines two years ago when it announced it had found a method to accurately determine the age of cells based on their physical properties. These properties include such factors as the cells’ ability to move and maintain flexibility and structure. That’s important because changes associated with aging at the physiological level – such as diminished lung capacity and grip strength – tend to be secondary to changes in the cells themselves, the researchers note.
“This means that measures of cell age could give us a more accurate picture of a patient’s health than his or her biological age,” explains Wirtz, the Theophilus Halley Smoot Professor of Engineering Science. “Eventually, we want to provide clinicians with a way to see aging in cells before a patient experiences age-related health decline, such as frailty.” That would open the door to intervene with recommended treatments and lifestyle changes (such as exercise or a better diet) or with specifically targeted biological agents to stave off the cellular aging and prevent chronic disease.
“Measures of cell age could give us a more accurate picture of a patient’s health than his or her biological age. Eventually, we want to provide clinicians with a way to see aging in cells before a patient experiences age-related health decline, such as frailty.” – Denis Wirtz, Johns Hopkins vice provost for research
In addition, Wirtz and Walston believe these new measurement technologies could be used to identify people in middle age, and even younger, who are at high risk of developing some chronic diseases and perhaps of aging at an accelerated rate.
Recognizing the promise in this approach, the National Institutes of Health recently awarded the team a $3.5 million grant to continue its efforts to develop cellular biomarkers for aging.
The team, which includes researchers from the Johns Hopkins Whiting School of Engineering and the Bloomberg School of Public Health, as well as the school of medicine, is now focusing on a structural network inside the cell’s nucleus that is known as the nuclear lamin.
Recognizing the promise in this approach, the National Institutes of Health recently awarded the team a $3.5 million grant to continue its efforts to develop cellular biomarkers for aging.
“The nuclear lamin is very important because it provides mechanical support to the cell, and it regulates cell functions such as cell division and DNA replication,” Wirtz explains. “We believe it influences a wide range of age-related characteristics.”
Don Willett May 7th, 2019
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The work and ideas of renowned Johns Hopkins psychologist Kay Redfield Jamison (and 2018 Miller Lecturer) moved farther into the international spotlight last fall, when it was announced that her most recent book, Robert Lowell: Setting the River on Fire, was a 2018 finalist for the Pulitzer Prize in biography, one of just three works to share that honor.
Described by the Pulitzer committee as “a superb examination of the life, work and struggles of Robert Lowell,” Jamison’s book explores the bipolar disorder that plagued the poet and helps readers better understand the relationship between mania and creativity.
Jamison has since created a special series on Psychiatry and the Arts. In November, Jamison – the Dalio Professor of Mood Disorders at Johns Hopkins – shared the Hurd Hall stage for a Q-and-A with film maker Paul Dalio, who was inspired by the psychologist’s book Touched by Fire to create a film by the same name that features two young poets with bipolar disorder who meet and fall in love while on a psychiatric unit. And in January, acclaimed actor Julian Sands (A Room with a View, The Killing Fields) came to the medical campus for a poetry reading of his favorite poems of Keats and Shelley.
Don Willett May 7th, 2019
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Debra L. Ness, president of the National Partnership for Women and Families, delivered the 16th annual Miller Lecture on May 7.
Ness is an innovative and sought-after health policy strategist who has helped shape the programs that are making health care in this country more accessible and affordable while improving health outcomes and delivering better-quality, more patient- and family-centered care. Under Ness’ stewardship, the national partnership has transformed the nation’s work-places. Today, 40 jurisdictions have adopted laws that allow workers to earn paid sick days, hundreds of corporations and five states have put paid family and medical leave programs in place, and dozens of states have adopted strong laws that prohibit and punish pregnancy discrimination.
Don Willett May 7th, 2019
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