ESPN reports on new ACL repair study
Taubman Emerging Scholar Asheesh Bedi, M.D., partners in clinical trail funded by billionaire Mark Cuban
Funding from the Mark Cuban Foundation, run by the well-known owner of the Dallas Mavericks, will allow University of Michigan scientists and physicians to study how human growth hormone may aid recovery from an ACL tear – one of the most frequent, traumatic and dreaded knee injuries among athletes.
Despite advances in surgical techniques and accelerated rehabilitation, the nearly quarter of a million patients who suffer ACL tears each year still experience permanent weakness and muscle loss. This weakness largely limits their ability to return to the same level of sport performance, and can increase their chances of developing painful osteoarthritis later in life.
The clinical trial that opened in 2015 will study if growth hormone can safely improve recovery and help to prevent long-term osteoarthritis and knee joint weakness after an ACL tear.
Read the ESPN article featuring Taubman Emerging Scholar Asheesh Bedi, MD, one of the trial's investigators. Dr. Bedi is the Harold and Helen W. Gehring Early Career Professor of Orthopaedic Surgery and an Assistant Professor of Sports Medicine and Shoulder Surgery at the University of Michigan and MedSport Program.
Arthritis drug may control kidney damage in patients with diabetes
U-M scientists’ lab work revealed cell-signaling target; partnership with drug company led to Phase II clinical trial
ANN ARBOR, Mich. – It started out as a treatment for arthritis. But steered by science, it could become a first new approach in two decades for treating the damage that diabetes inflicts on the kidneys of millions of people.
In a randomized, controlled Phase II study, the experimental drug baricitrinib reduced a key sign of kidney damage, with higher doses producing the largest effect, few side effects, and signs of sustained impact even after patients stopped taking it.
U-M researchers not only helped conduct the clinical study – their scientific discoveries set the trial in motion. It’s a fast-track example of the new treatment-development approach known as precision medicine.
The trial results come just three and a half years after the U-M research team linked up with the company that makes the drug, Eli Lilly & Co.
That connection resulted from the work of a team led by Matthias Kretzler, M.D. and Taubman Scholar Frank Brosius, M.D., which had worked for years to pinpoint the importance of a cell-signaling system called JAK-STAT in diabetic kidney disease.
By plowing through massive amounts of data on abnormal genetic activity in diseased human kidney tissue, and studying specially bred mice, the team showed JAK-STAT was over-active in multiple kidney cells damaged by diabetes.
But JAK-STAT also plays a key role in diseases where immune-system cells attack normal tissues – such as rheumatoid arthritis. Lilly scientists had developed baricitinib to calm the painful, inflamed joints of RA patients, and had received FDA permission to do trials that showed the drug’s safety and impact.
When they learned that Kretzler was scheduled to speak about his research to another group at Lilly, they went to his talk and raised the possibility of using baricitinib against diabetic kidney disease. The international clinical trial, which enrolled 129 adult patients, began quickly -- just 14 months after that meeting.
“This is the first example of implementing precision medicine in diabetic kidney disease, which affects 8 million Americans and will surely affect more as the growing diabetes epidemic continues,” says Kretzler. “It shows that the full translational research pipeline is in place, where we can study disease mechanisms, test our findings in model systems, identify drug candidates, find the right partners to take it to a clinical trial, and complete the trial – in 42 months.”
The trial showed baricitinib reduced a measure of kidney dysfunction called urinary albumin/ creatinine ratio or UACR, substantially compared with placebo after six months. It also showed that patients had lower levels of two compounds in urine or blood that indicate inflammation in the kidneys, called IP-10 and sTNFR2. The only significant side effect was mild anemia in the group that received the highest dose, which was expected based on previous research.
Brosius directed the animal research studies and co-led the multi-institutional clinical trial. He notes that treatment of diabetic kidney disease costs the U.S. billions of dollars yearly. Currently, the standard approach to treating kidney damage in people with diabetes is to control blood pressure using decades-old drugs called ACE inhibitors and ARBs.
Taubman Scholar Frank Brosius, M.D.
“The long-term effects of America’s obesity and diabetes epidemics means that millions more kidneys are at risk. So America urgently needs new approaches to stem the damage that diabetes inflicts on kidney cells,” says Brosius, who heads U-M’s Division of Nephrology and the Michigan Kidney Translational Core Center that helped support this work. “So does the world, as nations like China feel the effects of obesity and diabetes epidemics.”
Promise of university-industry cooperation
The new trial results are the first step in determining if baricitinib or other drugs that act on the JAK-STAT system could fight these effects. But they also show promise of combining basic university research, which can uncover specific targets for precise-acting drugs, with drug compounds developed by pharmaceutical companies.
Even drugs left on the shelf years ago, or already in use for other diseases, could be tested for new uses based on research findings from teams like the U-M group.
The U-M Medical School’s Business Development team helped make the linkage between U-M and Lilly possible, and has brokered other agreements under which companies sponsor research by U-M teams to find specific targets for drugs.
The basic research was funded by the National Institutes of Health, the A. Alfred Taubman Medical Research Institute, the European Union and the Juvenile Diabetes Research Foundation International. This includes the development of a bank of diseased kidney tissue taken during patient biopsies, the creation of a “humanized” mouse model, and high-level computing resources.
Other faculty members at U-M are looking for pathways involved in other ways that diabetes damages organs and tissues – from nerves to eyes. The approach, called systems biology, combines detailed studies of biological processes with advanced computing to create a computer model of a disease.
“Not only does system biology works for finding new drug targets and repurposing drug compounds that already have been tested safely in humans. It can work quickly,” says Kretzler.
George O’Brien Michigan Kidney Translational Core Center
U-M Medical School Office of Business Development
Abstract for baricitinib study results
Dr. Max Wicha receives $6.5 million to target cancer stem cells
Taubman Institute Deputy Director Max S. Wicha, M.D., has received a $6.5 million Outstanding Investigator Award from the National Cancer Institute to study cancer stem cells, the small number of cells within a tumor that fuel its growth and spread.
“With this kind of research, you don’t always know where it’s going next,” says Wicha, the Madeline and Sidney Forbes Professor of Oncology and founding director emeritus of the University of Michigan Comprehensive Cancer Center. “This new grant gives us the freedom to pursue new directions in cancer stem cell research.”
The award – roughly three times a traditional individual investigator award – is part of a new grant program called R-35 developed by the National Cancer Institute. The program will fund projects of unusual potential in cancer research over an extended period of seven years. The goal is to provide investigators with substantial time to break new ground or extend previous discoveries to advance biomedical, behavioral or clinical cancer research.
“The NCI Outstanding Investigator Award addresses a problem that many cancer researchers experience: finding a balance between focusing on their science while ensuring that they will have funds to continue their research in the future,” says Dinah Singer, Ph.D., director of NCI’s Division of Cancer Biology.
“With seven years of uninterrupted funding, NCI is providing investigators the opportunity to fully develop exceptional and ambitious cancer research programs.”
Wicha is one of the world’s foremost cancer stem cell researchers. He was part of the team that initially identified stem cells in breast cancer, the first time they had been described in a solid tumor.
Since then, Wicha’s lab has advanced the understanding of the role cancer stem cells play in the development of cancer and in treatment resistance. This has led to multiple clinical trials testing potential therapies aimed at attacking cancer stem cells.
“One of the challenges in the cancer stem cell field is that because they are a small percentage of the overall cells in a tumor, how do you know if you have killed them?” Wicha says.
His grant proposal involves isolating circulating tumor cells, cancer cells that break off from the primary tumor and circulate throughout a patient’s bloodstream. Using devices developed by engineering colleagues, the team will isolate and analyze the genome of individual cancer cells. Based on the markers expressed, the researchers can identify the portion of cells that are cancer stem cells to understand whether treatment is attacking the stem cells.
In addition, Wicha’s lab will work in coordination with other investigators to understand the role the immune system plays in cancer stem cells.
The single-cell assessment will be used to help determine which combination of stem cell-directed therapies and immunotherapies have the greatest potential for each patient. And if patients begin to relapse, could a blood test help identify that early on so that the patient can switch to a new treatment?
The project will focus on translating findings from the lab to the clinic, including developing clinical trials.
“This is an ideal time to take this work to the next level. We hope that the new Outstanding Investigator grant will help us make significant gains in understanding cancer stem cells to improve cancer treatment,” Wicha says.
Deadline extended to Feb. 15 for $100,000 Taubman Prize nominations
Nominations for the 2016 Taubman Prize for Excellence in Translational Medical Science will be accepted through February 15, 2016, the Taubman Institute has announced.
This award is presented annually by the A. Alfred Taubman Medical Research Institute at the University of Michigan. It is meant to recognize work in the crucial field of translational research being conducted by the clinician-scientist who has done the most to transform laboratory discoveries into clinical applications for patients suffering from disease.
- International scientists are eligible.
- U-M scientists are excluded.
- Self-nomination is permitted.
- The recipient must be available to deliver the keynote speech at the Taubman Institute annual symposium Oct. 21, 2016 in Ann Arbor, Mich.
For complete nomination materials, please click here.
An Evening of Art + Science 2016
For the third consecutive year, the Taubman Institute will host "An Evening of Art + Science" to raise funds for our innovative Emerging Scholars grants.
Held at Museum of Contemporary Art Detroit (MOCAD), this unique gala and auction will showcase works of art based on the lifesaving medical research of the Taubman Scholars, who have been paired with some of the regions' most talented artists to explore the process of creativity in both the studio and the laboratory.
Please plan to join us on April 21, 2016 to celebrate the intersecton of art and scientific discovery. Meet and mingle with leading contemporary artists and the eminent clinician-scientists of the Taubman Institute, who are leading the way toward new treatments and cures for cancer, diabetes, Alzheimer's disease, stroke and many more tough conditions.
Strolling dinner, signature cocktails, music and more will accompany the silent auction.
Ticket sales and other details are coming soon. Save the date!
Click to subscribe to the Taubman Institute E-newsletter for updates on "An Evening of Art + Science 2016."
Click to view a video about our past MOCAD event!
Taubman Prize awarded to Mahlon DeLong, M.D., of Emory University
Clinician-scientist developed Parkinson’s disease breakthrough
Ann Arbor, Mich. — A physician-scientist whose work has improved quality of life for tens of thousands of Parkinson’s disease patients is the recipient of the 2015 Taubman Prize for Excellence in Translational Medical Science, the University of Michigan’s A. Alfred Taubman Medical Research Institute announced.
Mahlon DeLong, M.D., Professor of Neurology at the Emory University School of Medicine, will receive the $100,000 prize in recognition of his contributions to the treatment of Parkinson’s disease.
DeLong’s research – spanning a 40-year career in medicine and science – identified the anatomical brain circuits involved in the clinical features of Parkinson’s disease and a novel target for surgical intervention, the subthalamic nucleus, a portion of the basal ganglia, brain structures located deep in the brain.
This finding paved the way for the application of high frequency deep-brain stimulation (DBS) of the subthalamic nucleus, a technique now used worldwide for advanced Parkinson’s disease patients. More than 100,000 individuals have received the treatment, which suppresses tremor and other motor impairments, and improves the ability to carry out the normal activities of daily living.
“Dr. DeLong’s contribution to improved care and quality of life for patients with devastating movement disorders is remarkable,” said Eva Feldman, M.D., Ph.D., director of the Taubman Institute, and the Russell N. DeJong Professor of Neurology at the U-M Medical School. “He exemplifies the ethos of the dedicated clinician-scientist. We are honored to recognize his extraordinary contributions by awarding him the Taubman Prize.”
DeLong was selected by a national panel of eminent medical science experts from among dozens of nominees for the Taubman Prize. Over decades he and his colleagues have mapped brain activity and deciphered the complex pathways and circuitry involved with the processing of motor functions, thoughts and emotions. Insights gained through his basic research, animal models and experiments eventually led to a clearer understanding of the abnormalities in brain circuits in animal models of Parkinson’s and how interruption of a key portion of the motor circuits could dramatically improve clinical features.
DeLong’s studies contributed greatly to the revival of surgical approaches for treating movement disorders. The development of the novel technique of high frequency deep-brain stimulation, using implanted electrodes, by Dr. Alim Louis Benabid in Grenoble, France, when applied to the subthalamic nucleus in patients with Parkinson’s produced a similar result as surgical interruption. DBS, because of its less invasive, reversible and adjustable features, rapidly replaced direct, irreversible destructive lesioning approaches.
DeLong, the William Timmie Professor of Neurology at Emory University School of Medicine, will present the keynote address at the Taubman Institute’s annual symposium on Oct. 16, 2015 at the Kahn Auditorium on the U-M medical campus. The symposium is open to the general public.
The Taubman Prize was established in 2012 to recognize outstanding translational medical research beyond the University of Michigan. It includes a $100,000 award and is presented each year to the non-U-M clinician-scientist who has done the most to transform laboratory discoveries into clinical applications for patients suffering from disease.
Previous recipients are:
2014: Carl June, M.D., of the Perelman School of Medicine at the University of Pennsylvania, for discoveries related to immunotherapy for leukemia using patients’ own T cells.
2013: Brian Druker, M.D., of the Oregon Health & Science University and Charles Sawyers, M.D., of Memorial Sloan Kettering Cancer Center, for their discoveries related to chronic myeloid leukemia.
2012: Hal Dietz, M.D., of Johns Hopkins University for his discoveries related to connective tissue disease.
About Mahlon DeLong, M.D.: DeLong is a key faculty leader of The Jean and Paul Amos Parkinson's Disease and Movement Disorders Research Program. He also is co-director and founder of ENTICe (Emory Neuromodulation and Technology Innovation Center), whose goal is to foster advancement of neuromodulation and the development of innovative neuromodulation technologies for the treatment of neurological and psychiatric disorders.
He is a member of the Institute of Medicine, a fellow of the American Academy of Arts and Sciences, a fellow of the American Association for the Advancement of Science (AAAS), an elected member of the Johns Hopkins Society of Scholars. He is scientific director of the Dystonia Medical Research Foundation and a member of the Scientific Advisory Board of the American Parkinson Disease Association.
DeLong received his undergraduate degree from Stanford University and his medical degree from Harvard University. He worked as a researcher at the National Institute of Mental Health at the National Institutes of Health (1968-1973) completed his residency in Neurology at Johns Hopkins School of Medicine and was a member of the Johns Hopkins faculty (1975-1989). In 1989 he joined Emory University School of Medicine, where he served as chair of the Department of Neurology (1989-2003).
DeLong has received numerous awards including the 2013 Breakthrough Prize in Life Sciences and the 2014 Lasker Award, which recognizes excellence in research aimed at curing intractable diseases and extending human life. He also received the 2009 American Academy of Neurology Movement Disorders Research Award and the 2008 Movement Disorders Society Lifetime Achievement Award.
He is a member of the Institute of Medicine, a fellow of the American Academy of Arts & Sciences, a fellow of the American Association for the Advancement of Science (AAAS), an elected member of the Johns Hopkins Society of Scholars, and is a past chair of the Society for Neuroscience. He is scientific director of the Dystonia Medical Research Foundation and a member of the Scientific Advisory Board of the American Parkinson Disease Association.
About the A. Alfred Taubman Medical Research Institute: In 2007 Michigan businessman, philanthropist and noted patron of the arts A. Alfred Taubman provided the initial funds to establish the institute bearing his name at the University of Michigan Medical School. Its mission is to provide the university’s finest medical scientists the freedom, resources and collaborative environment they need to push the boundaries of medical discovery, to produce breakthroughs in cures to speed the development of effective treatment for some of the most devastating illnesses. Currently, nearly 40 Taubman Scholars are advancing their research with the assistance of grants from the institute.
Dr. Max Wicha appointed to National Cancer Advisory Board
President Barak Obama announced his selection of Max S. Wicha, M.D., as one of five new appointees to the National Cancer Advisory Board.
Wicha, the Madeline and Sidney Forbes Professor of Oncology at the University of Michigan Comprehensive Cancer Center, will serve on the 18-member board for six years.
“I am honored that these talented individuals have decided to serve our country. They bring their years of experience and expertise to this Administration, and I look forward to working with them,” Obama said in a statement.
The NCAB and the President’s Cancer Panel are the only advisory bodies at either the National Institutes of Health or the Department of Health and Human Services whose members are appointed by the president. The primary task of the NCAB is to advise the secretary of Health and Human Services, the director of the National Cancer Institute, and ultimately the president of the United States on a range of issues affecting the nation’s cancer program and, specifically, NCI operations. The NCAB reviews and recommends grants and cooperative agreements following technical and scientific peer review.
Wicha founded the U-M Comprehensive Cancer Center and served as director for 27 years. He is a renowned cancer researcher who was part of the team that first identified cancer stem cells in a solid tumor, finding them in breast cancer. His lab continues to look at cancer stem cells to help improve treatments for metastatic breast cancer.
Wicha also serves as the deputy director of the A. Alfred Taubman Medical Research Institute.
Art auction helps expand Emerging Scholars Program
Two festive events have led to an expansion of the Taubman Institute's Emerging Scholars Program, said Eva L. Feldman, M.D., Ph.D., director of the institute.
Held in May, "Cures Are an Art Form" and "An Evening of Art + Science" each celebrated collaborations among Taubman Scholars -- U-M's eminent clinician-scientists -- and leading contemporary artists. The artists and scientists met for ab and studio tours, and discussions about the nature of ideas and curiosity and discovery in their respective fields. Then, the artists produced works of creativity inspired by the research of scholars working in fields as diverse as ophthalmology, dermatology, oncology and brain diseases.
The artwork was showcased at "Cures Are an Art Form" at Detroit's new nightclub Populux, and an online auction culminated May 14 during the gala "An Evening of Art + Science" at the Detroit Institute of Arts.
Through the sale of tickets, sponsorships and most importantly the original works of art, the Taubman Institute realized sufficient funds to expand the Emerging Scholars Program, which helps to support the up-and-coming generation of biomedical researchers.
"We are delighted that our second annual Evening of Art + Science was such a success," said Feldman. "Our deepest thanks to all who contributed and attended. I think we all enjoyed the opportunity to contemplate both art and science in new ways, and to enlarge our understanding of the intersection of both worlds. The monies we have raised will go directly to the support of early-career clinician-researchers, keeping the pipeline of new medical breakthroughs full for future generations."
Click here to view the photo gallery.
Taubman Scholar develops improved test for prostate cancer
Use of Mi-Prostate Score would reduce unneeded biopsies
Research led by Taubman Emerging Scholar Scott Tomlins, M.D., Ph.D., has led to a new urine-based test providing improved prostate cancer detection – including detecting more aggressive forms of prostate cancer – compared to traditional models based on prostate serum antigen, or PSA, levels.
The test, developed at the University of Michigan Comprehensive Cancer Center, is called Mi-Prostate Score, or MiPS. It combines PSA with two markers for prostate cancer, T2:ERG and PCA3, both of which can be detected through a urine sample. The test has been available clinically since September 2013.
“Around 50 percent of men who undergo a prostate biopsy will not have cancer. We need better ways to manage elevated PSA and determine who really needs to have a biopsy. MiPS gives men and their doctors better information to help make those decisions,” says lead study author Tomlins, assistant professor of pathology and urology at the University of Michigan Medical School.
The study looked at a total of 1,977 men who were undergoing prostate biopsy because of elevated PSA levels. Using urine samples, the researchers conducted MiPS testing and compared results to various combinations of PSA, PCA3, T2:ERG and other PSA-based risk calculators. They assessed how well the individual biomarkers and combinations of biomarkers predicted the likelihood of cancer and the likelihood of high-risk cancer – the aggressive type that needs immediate treatment.
The test reports individual risk estimates for prostate cancer and high grade cancer. Each patient’s personal threshold for choosing to undergo biopsy may vary, so there is no single cutoff for a “positive” result.
However, using one MiPS cutoff score to decide whether to biopsy patients would reduce the number of biopsies by one-third, while delaying the diagnosis of only about 1 percent of high-risk prostate cancers. The study is published in European Urology.
“MiPS gives men a more individualized risk assessment for prostate cancer, so that men concerned about their serum PSA levels can have a more informed conversation with their doctor about next steps in their care,” Tomlins says. A cost/benefit analysis of MiPS is being conducted.
PCA3 is approved by the U.S. Food and Drug Administration for prostate cancer risk assessment in men with a previous negative biopsy. Most of the men involved in this study were undergoing initial biopsy, suggesting MiPS can be useful earlier in the process.
The test is part of broader efforts at the University of Michigan to improve prostate cancer diagnosis, particularly detecting the type of cancer that requires immediate and aggressive treatment.
Mi-Prostate Score is available to anyone but requires a request from a doctor. For further information, call the University of Michigan's MLabs at 800-862-7284. Patients with questions about prostate cancer detection or treatment may call the U-M Cancer AnswerLine at 800-865-1125.
Information for those wishing to make a donation
At the Taubman Institute, we have been deeply touched by the calls and e-mails from individuals wishing to honor the life and legacy of A. Alfred Taubman through a donation to support lifesaving medical research.
To make a gift online via credit card, simply click here.
Checks made payable to the University of Michigan may be mailed to:
A. Alfred Taubman Medical Research Institute
109 Zina Pitcher Place
5017 A. Alfred Taubman Biomedical Science Research Bldg.
Ann Arbor, MI 48109-2200
For assistance, please phone: 734-615-7282
If you are interested in making a major gift to support the Emerging Scholars Program, please contact development officer Maria Muller at 734-355-5233 or
The University of Michigan has 501(c)(3) non-profit tax exempt status; our federal tax ID number is 38-6006309.
Our deepest thanks to all who have extended condolences and memorial tributes on the passing of Mr. Taubman.