News & Events
Science on Screen: See "Steel Magnolias" followed by Q&A with Dr. Eva Feldman at Ann Arbor's Michigan Theater
Twenty-five years after “Steel Magnolias”: Dr. Eva Feldman shares the latest in treatment of diabetes complications at the Michigan Theater’s April 16 session of Science on Screen
Twenty-five years ago, when millions of movie-goers laughed and then cried over the saga of M’Lynn, her diabetic daughter Shelby and their eccentric friends and relatives in “Steel Magnolias,” about 6.3 million Americans were living with diabetes.
Today, nearly 26 million Americans have diabetes -- and if unchecked, the rising incidence of the disease will affect one in every three Americans by 2050, according to the American Diabetes Association. The cost of diabetes is estimated at more than $250 billion a year in the United States alone and the non-monetary cost to quality of life for patients and their families is immeasurable.
Diabetes has adverse effects on the entire body, from heart to kidneys to eyes. And the neurological complications of diabetes can be particularly debilitating. As many as 70 percent of diabetics suffer some form of nervous system damage, leading to pain, loss of sensation and loss of mobility. Currently, no effective treatment exists for this nerve damage.
But there is hope.
Dr. Eva Feldman, the Russell N. DeJong Professor of Neurology at the University of Michigan Medical School and the director of the A. Alfred Taubman Medical Research Institute, is a practicing neurologist whose research laboratory seeks new discoveries about the cause and treatment of diabetic neuropathy and other complications.
Her laboratory, the Program for Neurology Research & Discovery, is attacking this huge health problem in many ways. PNR&D scientists are discovering how high blood sugar injures nerves, why this causes pain, and how over time diabetes destroys the nerves. By simulating the insults that nerve cells undergo with diabetes in cultured cells, and studying neuronal changes in patients with diabetic neuropathy, Dr. Feldman and her staff has discovered some of the key mechanistic pathways involved in neuronal injury during diabetes. These pathways have become the subjects for development of new, groundbreaking therapies.
Join Dr. Feldman for the April 16 installment of Science on Screen, the innovative series at Ann Arbor's historic Michigan Theater that pairs films with expert guest speakers for the perfect combination of entertainment and enlightenment. Following the 7 p.m. showing of “Steel Magnolias,” Dr. Feldman will share the latest developments in treatment and take questions from audience members.
Visit the Michigan Theater website for additional information.
Winter/Spring Visiting Professor series features eminent guest speakers
The Taubman Institute's Visiting Professor lecture sreies -- which assists in bringing eminent, thought-leading scientists from around the globe to speak to the U-M community -- continues this year with a stellar line-up of speakers, including:
Steven A. Goldman, M.D., Ph.D., University of Rochester Medical Center
10:30 to 11:30 a.m. in the Danto Auditorium of the U-M Cardiovascular Center
Justin McArutheru, MBBS, MPH, Johns Hopkins University
10:30 to 11:30 a.m. in the Danto Auditorium of the U-M Cardiovascular Center
David M. Nathan, M.D., Harvard University
1-2 p.m. in the U-M Hospital's Ford Auditorium
Martin Turner, M.D., Oxford Unversity
4-5 p.m. in the MCHC Auditorium (Mott Children's Hospital)
Inaugural Emerging Scholars Symposium slated for April 30
Taubman Institute announces inaugural Emerging Scholars Symposium to take place April 30
One of the most innovative of the “high-risk, high-reward” grant programs at the A. Alfred Taubman Medical Research Institute is the Emerging Scholars Program, which often is referred to as the “jewel in the crown” of the institute’s initiatives.
Not only do these grants support the current work of the best and brightest of the early-career clinician-scientists on the U-M Medical School faculty, they achieve the crucial goal of keeping our health science research pipeline full.
Talented, passionate physician-researchers with the vision and energy to solve complex medical puzzles should not be deterred for lack of funds. Thanks to the contributions of the generous donors who have pledged three years of funding for each scientist, the institute now is jump-starting the careers of 11 Emerging Scholars who combine their patient practice with cutting-edge research into cancer, neurological disorders and other complex diseases.
And now, the first-ever Emerging Scholars Symposium will present a morning of science featuring presentations by six of our remarkable Emerging Scholars, who are seeking new discoveries and treatments in fields ranging from ovarian cancer to major depression.
The Emerging Scholars Symposium will run from 10 a.m. to noon in the Kahn Auditorium of the A. Alfred Taubman Biomedical Science Research Building at U-M. For a map to the AAT-BSRB, click here.
The symposium is open to the entire University of Michigan community and to the general public. No registration is required.
To view a short video about the Emerging Scholars program, click here.
Ten Taubman Scholars named to "Best Doctors in America" roll
The following Taubman Scholars and Emerging Scholars are among the University of Michigan Medical School physicians recently named to the 2013-2014 "Best Doctors In America" list.
Frank (Chip) Brosius III, M.D.
Valerie P. Castle, M.D.
Sung Won Choi, M.D.
Eva L. Feldman, M.D., Ph.D.
Thomas W. Gardner, M.D., M.S.
Johann Gudjonsson, M.D., Ph.D.
Alon Kahana, M.D., Ph.D.
Theodore S. Lawrence, M.D., Ph.D.
Parag Patil, M.D., Ph.D.
Max S. Wicha, M.D.
The new national list includes 493 U-M physicians — and places them among the best 5 percent of doctors in their specialties. UMHS has more physicians recognized than any other health system in Michigan.
The list is compiled every year by Boston-based Best Doctors, Inc., and based on an in-depth survey, the List contains more than 53,000 U.S. physicians in 40 specialties and more than 400 subspecialties of medicine. In a confidential review, current physician listees answer the question, “If you or a loved one needed a doctor in your specialty, to whom would you refer?”
This yields a preliminary set of doctors who meet the initial criteria for inclusion. These physicians are then checked for credentials, disciplinary actions and clinical activity. Only doctors who meet all evaluation criteria are selected for the list.
A full list of the UMHS doctors on this year’s list is available at http://umhealth.me/bestdoc14.
Taubman Institute Founder & Director to receive ALS award
The ALS Association Michigan Chapter has named Mr. A. Alfred Taubman, founder and chair of the A. Alfred Taubman Medical Research Institute, and Eva L. Feldman, M.D., Ph.D., the institute’s director, as the 2014 recipients of the association’s Legacy of Hope Award.
The award honors individuals who effect positive changes within the ALS community and demonstrate a remarkable commitment to the betterment of treatment for ALS patients, and the research necessary to find the cure for ALS.
Through his establishment of the Taubman Institute at the University of Michigan, as well as for his philanthropic support of Dr. Feldman’s laboratory, Mr. Taubman has created an environment where scientists are working on ALS-related research ranging from imaging techniques to provide early diagnosis, to Dr. Feldman’s landmark trial of a first-ever stem cell treatment for ALS. To date, 22 patients have received injections of specially engineered stem cells directly to their spinal cords in the FDA-approved trial, which is testing the ability of the stem cells to replace dying motor neurons.
“Mr. Taubman and I are deeply grateful to be selected as the inaugural recipients of this honor,” said Dr. Feldman. “We greatly appreciate the recognition of our work at the Taubman Institute to create hope for ALS patients and their families, and are proud to accept it as representatives of the many other researchers, philanthropists and caregivers striving every day in the quest for new cures and treatments.”
Dr. Feldman and Mr. Taubman will be honored at the Legacy of Hope evening sponsored by the ALS Association Michigan Chapter on April 3. The black-tie gala featuring a reception, dinner, auction and awards program will be held at the Townsend Hotel in Birmingham beginning at 6 p.m.
For information about tickets and sponsorship opportunities, visit www.alsa-michigan.org or call (248) 680-6540.
Taubman Scholar Dr. Max Wicha: Study sheds light on 'triple-negative' breast cancer
ANN ARBOR, Mich. New research from the University of Michigan Comprehensive Cancer Center and Georgia Regents University finds that a protein that fuels an inflammatory pathway does not turn off in breast cancer, resulting in an increase in cancer stem cells. This provides a potential target for treating triple negative breast cancer, the most aggressive form of the disease.
The researchers identified a protein, SOCS3, that is highly expressed in normal cells but undetectable in triple-negative breast cancer. They showed that this protein is degraded in cancers, blocking the cellular off-switch of a feedback loop involving the inflammatory protein interleukin 6, IL6. When the switch does not get turned off, it enables cancer stem cells to grow.
"We have known for a long time known that there are important links between inflammation and cancer, including similar pathways that regulate normal and cancer stem cells," says study author Max S. Wicha, M.D., distinguished professor of oncology and director of the U-M Comprehensive Cancer Center.
"This work helps explain why these pathways shut off in normal tissues after injury but remain active in cancers, resulting in an increase in cancer stem cells. Furthermore, they suggest that blocking these inflammatory loops may be a means of targeting cancer stem cells, improving patient outcome," says Wicha, a Senior Scholar at the A. Alfred Taubman Medical Research Institute.
The study appears in the Nature journal Oncogene.
Currently, there are no molecularly targeted therapies aimed at triple-negative breast cancer, which is a type of cancer negative for estrogen receptor, progesterone receptor and the HER2 protein – all key targets for current therapies. Patients with this form of disease tend to have worse outcomes.
The researchers tested a drug, bortezomib, in mouse models of triple-negative breast cancer and found that it stops the protein degradation, resulting in the inflammatory loop shutting off, which reduces the cancer stem cells, thereby blocking metastasis. Bortezomib is currently approved for treatment of the blood cancer multiple myeloma.
This team previously showed that IL6 can stimulate breast cancer stem cells in HER2-positive breast cancers and they are designing a clinical trial which uses an IL6 blocker. The new research suggests that adding bortezomib to the IL6 inhibitor may be a way to target stem cells in triple-negative breast cancer.
"Now that we unveiled how inflammation is regulated in triple-negative breast cancer, we expect that our studies can be translated into the clinic. The drugs used to block these chemical messengers are already approved for the treatment of rheumatoid arthritis and other inflammation-related diseases, which should facilitate their use in cancer," says study author Hasan Korkaya, Ph.D., assistant professor at the Georgia Regents University Cancer Center.
More laboratory testing is needed before a clinical trial can begin. The researchers also suspect that this pathway may apply to other cancers as well and are investigating that further.
ALS stem cell trial milestone: 25th surgery performed
ANN ARBOR, Mich. — A patient with amyotrophic lateral sclerosis (ALS) received six million stem cells injected to the spinal cord in a procedure Jan. 8 at the University of Michigan Health System – the 25th time an ALS patient has undergone the experimental injections as part of a national clinical trial.
The 66-year-old man has returned home and will receive follow-up monitoring and testing to help U-M neurologists assess the safety and any potential effect of the injections. He is the 7th patient to undergo the surgery in Phase 2 of the trial, which began in September and follows a 15-patient Phase 1 trial that produced no adverse side effects in patients undergoing the surgery.
Eva L. Feldman, M.D., Ph.D., the Russell N. DeJong Professor of Neurology at the U-M Medical School and director of the A. Alfred Taubman Medical Research Institute, is the principal investigator for the trial. Feldman has led the analysis of results from the Phase 1 trial which concluded in 2012.
In Phase 1, three of the 15 patients received a second injection of stem cells, for a total of 18 surgeries in that segment of the trial. The seven surgeries so far in Phase 2 bring the total number to 25.
“We’re pleased that as we reach this important milestone, none of our patients in either phase of the trial have experienced any adverse side effects as a result of the stem cell implantation,” said Feldman. “We are very excited to note that escalating the number of stem cells per patient does not appear to increase that risk.”
In data presented in 2013, spinal cord injections of between 500,000 to 1.5 million cells were delivered safely and tolerated well in a Phase 1 trial conducted at Emory. The researchers reported possible signs that in one subgroup of participants who received the highest dose of stem cells, ALS progression may have been interrupted.
Additional patients with the condition, also known as Lou Gehrig’s disease, are being evaluated for possible participation in the trial at U-M and Emory University. Patients in the Phase 2 trial will receive up to 16 million of the specially engineered stem cells.
The Phase II trial is approved by the U.S. Food and Drug Administration and funded by Neuralstem, Inc., the Maryland-based company whose stem-cell product the trial is testing. It seeks to study any effect that injected stem cells might have on motor neurons – muscle-controlling nerve cells that die in ALS patients, eventually robbing them of the ability to walk, speak and breathe.
Parag Patil, M.D., Ph.D., a U-M neurosurgeon and biomedical engineer, performed the four operations that have been completed at U-M. In each case, the patient’s spinal column was unroofed and the spinal cord exposed to receive the cells. The cells are introduced via a custom-designed delivery device that is affixed to the subject’s spinal bones so that it moves with the patient’s breathing throughout the process.
Patil, an assistant professor in U-M’s departments of Neurosurgery, Neurology, Biomedical Engineering and Anesthesiology, and a Young Friends of the Taubman Institute Emerging Scholar, also serves as a paid engineering consultant to Neuralstem to further develop the cell-delivery device.
This Phase 2 dose escalation trial is designed to treat up to 15 ambulatory patients in five different dosing cohorts, under an accelerated dosing and treatment schedule.
The first 12 patients, divided into four cohorts, will receive injections only in the cervical region of the spinal cord, where breathing function is controlled. The first cohort of three patients received 10 cervical region injections of 200,000 cells per injection. The second cohort of three patients received 20 cervical region injections of 200,000 cells per injection. The trial has now progressed to the third cohort of three patients receiving 20 cervical injections of 300,000 cells per injection. If this proves safe, the fourth cohort will receive 400,000 stem cells per injection with 20 cervical injections.
The last three Phase 2 patients will receive injections in both the cervical and the lumbar spinal regions. These patients will receive 20 injections of 400,000 cells each in the lumbar region in addition to the 20 injections they will already have received in their cervical region.
The trial also accelerates the treatment schedule, and is designed to progress at the rate of one cohort per month with one month observation periods between cohorts. Researchers expect all of the patients could be treated by the end of the second quarter in 2014.
Patients seeking information on the trial should contact the relevant center. For the University of Michigan Health System, please visit: http://www.umclinicalstudies.org/HUM00072488. For Emory Healthcare, please call (404) 778-7777.
Taubman Scholar Dr. Max Wicha: Two types of cancer stem cells lead to metastasis
ANN ARBOR, Mich. — Breast cancer stem cells exist in two different states and each state plays a role in how cancer spreads, according to an international collaboration of researchers. Their finding sheds new light on the process that makes cancer a deadly disease.
“The lethal part of cancer is its metastasis so understanding how metastasis occurs is critical,” says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the University of Michigan Comprehensive Cancer Center. “We have evidence that cancer stem cells are responsible for metastasis – they are the seeds that mediate cancer’s spread. Now we’ve discovered how the stem cells do this.”
First, on the outside of the tumor, a type of stem cell exists in a state called the epithelial-mesenchymal transition (EMT) state. These stem cells appear dormant but are very invasive and able to get into the bloodstream, where they travel to distant parts of the body.
Once there, the stem cells transition to a second state that displays the opposite characteristics, called the mesenchymal-epithelial transition state (MET). These cells are capable of growing and making copies of themselves, producing new tumors.
“You need both forms of cancer stem cells to metastasize and grow in distant organs. If the stem cell is locked in one or the other state, it can’t form a metastasis,” says Dr. Wicha, who is a Taubman Senior Scholar.
The findings, which are published in the January issue of Stem Cell Reports, raise a number of questions about how to treat or prevent metastatic breast cancer. Researchers must now understand whether new therapies must attack both forms of the stem cell to be successful. Different pathways regulate each type of stem cell, which suggests that effective therapies must be able to target multiple pathways.
In addition, current tests that look at tumor cells circulating in the blood to help determine whether the cancer is spreading do not appear to capture the EMT stem cells, which are the cancer cells that travel through the blood. U-M researchers are working with colleagues from the U-M College of Engineering to develop new tools to isolate the EMT stem cells from the blood of cancer patients.
“Now that we know we are looking at two different states of cancer stem cells, we can use markers that distinguish these states to get a better sense of where the cancer stem cells are and to determine the effectiveness of our treatments,” Dr. Wicha says.
The study looked specifically at breast cancer stem cells but the researchers believe the findings likely have implications for other cancer types as well.
Taubman Emerging Scholar's research leads to better bone marrow transplant outcomes
Improving the results of bone marrow transplants in people with cancer is the quest of Sung Won Choi, M.D., a Taubman Emerging Scholar, oncologist and assistant professor of pediatrics at the University of Michigan Medical School.
And newly published results of Dr. Choi's work suggest that a treatment she and other U-M researchers tested in patients can drastically cut the risk of graft-vs.-host disease, a deadly side effect of the potentially life-saving bone marrow transplants.
The study, the first to test this treatment in people, combined the drug vorinostat with standard medications given after transplant, resulting in 22 percent of patients developing graft-vs.-host disease compared to 42 percent of patients who typically develop this condition with standard medications alone. Results of the study appear in The Lancet Oncology.
"Graft-vs.-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years. This study has us cautiously excited that there may be a potential new way to prevent this condition," says Choi, whose research is supported in part by an annual Emerging Scholars Grant from the A. Alfred Taubman Medical Research Institute.
Vorinostat is currently approved by the U.S. Food and Drug Administration to treat certain types of cancer. But U-M researchers, led by senior study author Pavan Reddy, M.D., found in laboratory studies that the drug had anti-inflammatory effects as well -- which they hypothesized could be useful in preventing graft-vs.-host disease, or GVHD, a condition in which the new donor cells begin attacking other cells in the patient's body.
The study enrolled 61 older adults from the University of Michigan and Washington University in St. Louis who were undergoing a reduced-intensity bone marrow transplant with cells donated from a relative. Patients received standard medication used after a transplant to prevent GVHD. They also received vorinostat, which is given as a pill taken orally. Fifty of the 61 participants completed the full 21-day course of vorinostat.
The researchers found vorinostat was safe and tolerable to give to this vulnerable population, with manageable side effects. In addition, rates of patient death and cancer relapse among the study participants were similar to historical averages.
The results mirror those found in the laboratory using mice. Reddy, the Moshe Talpaz Professor of Oncology and professor of internal medicine at the U-M Medical School, has been studying this approach in the lab for eight years.
"This is an entirely new approach to preventing graft-vs.-host disease," Reddy says. Specifically, vorinostat targets histone deacetylases, which are different from the usual molecules targeted by traditional treatments.
"Vorinostat has a dual effect as an anti-cancer and an anti-inflammatory agent. That's what’s potentially great about using it to prevent graft-vs.-host, because it may also help prevent the leukemia from returning," says Reddy, who is also co-director of the hematologic malignancies and bone marrow transplant program at the U-M Comprehensive Cancer Center.
"We are encouraged by our findings," Choi says. "Vorinostat combined with standard graft-vs.-host disease prophylaxis after related-donor transplant appears to be safe and associated with lower than expected incidence of acute GVHD. Future studies are needed to assess the effect of vorinostat in broader transplant settings. We are currently investigating vorinostat plus standard therapies to prevent GVHD in transplants with an unrelated donor."
For information about this clinical trial, call the U-M Cancer AnswerLine™ at 800-865-1125.
Source: The University of Michigan Health System
Fall-Winter Visiting Professor lineup features experts in lung, muscle and nerve disorders
The Fall 2013 schedule of Taubman Institute Visiting Professor Lectures, which are held in conjunction with departments of the University of Michigan Medical School, features distinguished scientists from institutions around the world, who have been invited by Taubman Scholars and other faculty members to address the U-M community.
Visiting Professor Lectures are generally held monthly and represent the Taubman Institute's ongoing commitment to furthering translational medical research by creating opportunities for the most talented physician-researchers to exchange knowledge and ideas.
Upcoming events in 2013 include:
Oct. 17: Jann Sarkaria, M.D., of the Mayo Clinic, whose research targets the fatal brain tumor glioblastoma.
Oct: 21: Kurt Stenmark, M.D., a pediatric pulmonology expert from the University of Colorado Denver.
Oct. 23 Andrew Mammen, M.D., Ph.D., whose research targets muscle diseases such as myositis, from the Johns HopkinsSchool of Medicine.
Mar. 19, 2014 Steven A. Goldman M.D., Ph.D., an expert in neurodegenerative diseases from the University of Rochester Medical Center.
More information about each lecture will be posted as it becomes available.
Click here to view video interviews of past visiting professors.
10 Taubman Scholars named to "Best Doctors in America" list
They're among 493 U-M physicians to receive the honor from their peers
Click here for the list.
People who care
ALS Association Michigan Chapter honors institute
Founder A. Alfred Taubman and Director Dr. Eva Feldman to receive inaugural award at April 3 gala
Click here for details
U-M offers new early detection prostate cancer test
Research by Taubman Scholar Dr. Arul Chinnaiyan has let to the development of a new test for prostate cancer that is far more accurate than the standard PSA test, the University of Michigan has announced.
Click here to read more.
news & events
New Taubman Prize trophy debuts
The new trophy for the Taubman Prize for Excellence in Translational Medical Research, which was designed in consultation with institute founder Mr. A. Alfred Taubman, was presented at the institute's Oct. 11 symposium. The modern sculpture was created using a novel 3D printing technique.
Drug cuts risk of bone-marrow transplant side effect
Taubman Emerging Scholar Sung Won Choi, M.D., is the lead author of a new study that finds a new way to help prevent graft-vs-host disease in cancer patients receiving bone-marrow transplants.
Study: Two types of cancer stem cells lead to metastasis
Breast cancer stem cells exist in two different states and each state plays a role in how cancer spreads, according to a new study published by Taubman Senior Scholar Dr. Max Wicha.