by Christina Crowe
In this series, we spotlight several researchers in the Department of Pathology who hold endowed professorships and, in one case, a chair. We recognize each of these individuals for his or her dedication to and innovation in their respective fields of study.
The next individual we focus on in our series of researchers holding endowments is Shu Chen, Ph.D. Dr. Chen is a Professor in the Division of Neuropathology at UAB Pathology, holding joint faculty appointments in Neurobiology, and Biochemistry and Molecular Genetics. He is a senior scientist with UAB’s Alzheimer’s Disease Center, the Center for Clinical and Translational Science, and the Center for Neurodegeneration and Experimental Therapeutics.
It may not be commonly known that the only definitive way to diagnose Alzheimer’s disease and related dementias is through autopsy of the deceased patient’s brain. As our population increasingly ages the incidence of these diseases is on the rise, and early diagnosis is key to improving treatments. At UAB, Shu Chen, Ph.D., is working to create tools that will aid in those diagnoses.
Chen joined the Department of Pathology at UAB in December 2021 as a professor in the Division of Neuropathology from Case Western Reserve University in Cleveland, Ohio, where he was a professor and served as the associate director of the National Prion Disease Pathology Surveillance Center from 2003 to 2008.
“The prion protein is a normal protein we are born with, but in diseases like Mad Cow, it occludes the normal protein onto a template and becomes aggregated,” Chen says. “It’s similar to ice forming: These prion ‘seeds,’ or isoforms, recruit and grow more seeds, then have exponential growth of elongated amyloid fibroids.”
In Alzheimer’s and similar diseases the proteins behave “prion-like,” Chen explains, “with the seeding template, and accumulate in certain areas of the brain.” Each of these diseases is marked by the massive accumulation in the brain of amyloid proteins—a common theme of neurodegenerative diseases.
While the function of these proteins is not completely understood, studying their reactions may help researchers such as Chen create a better comprehension of the plaques and tangles that build up in the brain with Alzheimer’s disease and dementia, in turn leading to earlier and more effective treatments.
“There is an urgency of diagnosis in these diseases—it would be very helpful to have a molecular or biomarker assay that would help get to a diagnosis before the patients are dying,” he says.
Dr. Chen is, in fact, one of the first to elucidate the structural differences in prion proteins that cause distinct human prion diseases. He is an expert on the pathogenesis of Parkinson’s disease associated with LRRKS mutations. Chen’s current research focuses on biomarkers for Parkinson’s disease, Lewy body dementia, and Alzheimer’s disease
“My research started with human prion diseases and now has expanded to include molecular, genetic and translational studies of more common brain disorders, such as Parkinson’s disease, dementia with Lewy bodies, and Alzheimer’s disease,” he says.
“Our cells make these proteins from the time we are born, but somehow during aging these proteins become aggregated and the cells aren’t turned over as they normally would be,” Chen explains. “They accumulate and become deposited in the brain—the hallmark of all these diseases.”
His current research focus is devoted to the identification of biomarker and genetic modifiers of neurodegeneration. A major problem with dementia and related diseases is the occurrence of overlapping symptoms, and not understanding the root cause of the diseases—making early diagnosis very difficult.
“We hope to develop a biomarker assay to detect this disease because we cannot peek into the brain, but we can use specimens that are easily accessible in peripheral tissue like the skin, cerebral spinal fluid, or nasal mucosa. We try to look for aggregated protein that occurs in peripheral tissue that would be indicative of disease,” he says.
He and his team developed a sensitive assay to determine whether protein accumulation is taking place. They validated the assay using autopsy tissue, “because with autopsy the diagnosis is definitive, so we have very good specificity.”
“Early diagnosis is very important for patient care and for clinical trial development,” he says. “We would like to develop an assay when people are in the pre-|linical stage so we can diagnose them and follow their progression, because therapeutics work better when they’re started earlier.”
Chen is one of the most highly-funded neuropathology researchers in the US (as evidenced by his ranking in the top 10% of the annual Blue Ridge Rankings of funded Principle Investigators for 2022), supported by two R01s and a U01 award focusing on biomarkers for Parkinson’s disease, Lewy body dementia, and Alzheimer’s disease, from the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). He is also supported by the NIA for an R01 on computational prediction, network analysis and genetic screening in C. elegans to uncover neurodegenerative causes in Alzheimer’s disease.
This spring, Chen learned he will receive another R01 to study, “Peripheral Biomarkers for Early Diagnosis of Mixed Pathologies in AD/ADRD” from the NIA. The goal of this $3.67 million, five-year study is to develop and validate diagnostic biomarkers for Alzheimer’s disease and related dementias such as tauopathies, Lewy body dementia, and their comorbidities using easily accessible peripheral tissues.
“Our study may ultimately help early diagnosis to improve patient care and aid the development of therapeutics for patients living with dementias,” Chen says.
From Colder Climates to the Deep South
Chen and his family decided to move to the south and join UAB Pathology in 2021, and moved before the winter storms ravage the north at the end of the year.
“One of the more attractive points for me to move here is that UAB makes it easy for productive collaboration among faculty in various departments,” he notes. Rati Chkheizde, M.D., Assistant Professor, Neuropathology, is among Chen’s collaborators. Chen is also working with David Standaert, M.D., Chair of the Department of Neurology, David Geldmacher, M.D., Professor and Senior Scientists, Integrative Center for Aging Research, and Erik Roberson, Ph.D., M.D., Director of the Alzheimer’s Disease Research Center, as well as with Marissa Natelson Love, M.D., Associate Professor, and her clinic staff in the Department of Neurology who are working to recruit patients for their studies. Participants in these studies will undergo rigorous neurological examinations while donate blood and skin biopsy samples. These specimens will be assayed in Dr. Chen’s lab to detect protein changes that accompany neurodegeneration. The combination of clinical data and molecular measures of protein abnormality in easily accessible specimens will facilitate the accurate diagnosis of neurodegenerative disorders.
“Scientific collaboration is a distinct advantage here at UAB, because you are welcomed and you can get the job done working with other researchers. In this world of medicine, you need that in order to advance the field.”
In addition to his research, Chen is a proponent and practitioner of mentoring students and trainees—both in his time before UAB and since arriving. He has been a faculty mentor throughout his career. Chen recently obtained Graduate Biomedical Sciences status that allows him to serve as a faculty advisor for graduate students, and is in the process of recruiting students to his lab.
UAB Pathology established the Ona Faye-Petersen Endowed Professorship in 2021 in recognition of Dr. Faye-Petersen, earned emeritus status in August of 2020 after semi-retirement. In 2019 she established the Ona M. Faye-Petersen Educational Support Fund, which provides funds for supplemental learning opportunities for trainees in Anatomic Pathology. The endowment was awarded to Dr. Chen in June 2022, and he expresses his gratitude for the support it provides.
“This endowment helps elevate the awareness of our research, and I am very proud and very fortunate to have it,” he says. “I hope it enhances the visibility of our division and that we study neurodegenerative diseases such as Alzheimer’s disease and other dementia-related diseases. In turn, I hope this helps to increase faculty recruitment into our specialty area.”
“I am extremely honored that this Endowed Professorship was awarded to Dr. Chen and supports his critical research in the early detection and treatment of Alzheimer’s disease and the terrible related debilitating disorders that rob so many of the richness of their lives,” Faye-Petersen says.
Chen also thanks his division director, C. Ryan Miller, M.D., Ph.D., Vishnu B. Reddy Translational Research Endowed Professor, and George Netto, M.D., Robert and Ruth Anderson Endowed Chair, UAB Pathology, for their strong and enthusiastic support.
“Dr. Chen is a wonderful addition to our neuropathology team, having brought his distinct expertise to UAB,” Netto says. “His research is poised to make important advances in the ways in which we are able to diagnose and treat neurodegenerative diseases such as dementia.”