November 16, 2018
Driving research that will lead to more personalized therapies and patient care is the focus of the latest A. Alfred Taubman Medical Research Institute grants program, which recently announced its first two awardees.
The $1 million initial grants — with potential additional funding at future milestones — will support interdisciplinary teams of researchers exploring medical challenges related to the immune system.
“Present medical care is limited in its ability to provide individualized treatment or prevention of disease,” said Charles F. Burant, director of the Taubman Institute. “In part, this is due to a relatively small number of clinical measurements that are used to quantify relative health, and to predict disease onset, relapse and response to treatment.”
The ability to phenotype patients is often limited by space, clinician time, support personnel, clinic demands, phenotyping infrastructure, database availability, bioinformatics support, and other factors that are difficult to put into place.
The Taubman Institute — which was established at the University of Michigan in 2008 to support Michigan Medicine’s physician-investigators — hopes to help fill these gaps, Burant said.
Why patient response varies
The first Taubman Institute Innovation Project grant goes to a project nicknamed PerMIPA and is headed by Michelle Kahlenberg, associate professor of internal medicine, and Johann Gudjonsson, Arthur C. Curtis Professor of Skin Molecular Immunology and associate professor of dermatology.
Each is a prior recipient of the Taubman Emerging Scholar grants that help junior Medical School faculty establish their research programs. Both physicians care for patients at Michigan Medicine in addition to running their laboratories.
Kahlenberg is a rheumatologist who investigates lupus, a systemic autoimmune disease that occurs when the body’s immune system attacks its own tissues and organs. Gudjonsson is a dermatologist who specializes in autoimmune skin diseases such as psoriasis.
Hundreds of patients being seen at U-M clinics for lupus and psoriasis will be invited to join the study by providing tissue and blood samples, and detailed medical histories, at various points in their treatment. Samples will be analyzed at the cellular, genetic and molecular levels.
PerMIPA leaders hope to attract other grants or industry partnerships to expand this five-year study to other autoimmune or inflammatory diseases.
“This incredible support by the Taubman Institute will allow us to take steps towards addressing how factors such as age, genetics, gender and race affect the immune system and how these factors affect the course and treatment responses in our patients,” Gudjonsson said.
“It will establish and accelerate a foundation for a personalized approach for the treatment of autoimmune disorders, and revolutionize our capabilities to manage patients with these devastating and frequently challenging diseases.”
Finding the ‘holy grail’ of immune suppression
Drugs that suppress the immune system keep the body from rejecting the donated organ, but they also lower the patient’s ability to fight off infections. Immune suppression can increase the risk of certain cancers, as the normal immune system is responsible for vigilantly removing such cells.
Finding the right balance for individual patients is the aim of a TIIP-supported study to refine the use of immunosuppressants in individuals undergoing heart, kidney, liver or lung transplantation.
It’s headed by Daniel Goldstein, Eliza Maria Mosher Collegiate Professor of Internal Medicine, professor of internal medicine, of microbiology and immunology, and research professor at the Institute of Gerontology, and will be supported by a multidisciplinary team including experts in immune monitoring, bioinformatics and statistics.
Blood and organ tissue samples from Michigan Medicine patients who join the study will be analyzed using a new immune phenotyping process called mass cytometry, which can examine up to 40 different immune function-related parameters on a single cell.
“We will be taking patient samples in the early stage of transplantation and surveying their immune system at a level not done before in transplantation studies,” Goldstein said.
Tissue collected from patients also will be used to create a central biorepository for use by other researchers.
In studying all solid organ transplant patients, no matter what organ is being replaced, the team will be able to gain information more quickly about the adverse effects of suppression drugs, Burant said.
“Finding a better way to optimize the dosage of immune suppressive drugs takes us further in the direction of the personalized patient care that truly is the future of medicine,” he said.