Medical research in the news

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Researchers receive $1,894,271 grant to address new drug targets for diastolic dysfunction

After the left ventricle of the heart contracts, it must relax efficiently to prepare to refill and supply the body with blood on the next beat.  An increasing number of patients — including nearly all patients with heart failure — suffer from impaired relaxation, which is part of a clinical syndrome known as diastolic dysfunction. Currently, treatments for impaired relaxation do not exist. A team of Wayne State University School of Medicine researchers led by Charles Chung, Ph.D., assistant professor of physiology, recently received a $1,894,271 grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health to address the critical need for new drug targets and diagnostic indexes for diastolic dysfunction using novel biomechanical tests that ultimately can be translated into clinical practice. According to Chung, the project was inspired by his research team’s finding that how quickly the heart’s muscle moves is directly related to how fast the muscle can relax. The project will use unique experiments and imaging techniques to link mechanical properties of the heart with models of heart failure that occur in patients. “My lab’s main research focus is to understand how the heart muscle moves at the end of contraction and how this motion can speed up the force decline, or relaxation, of the muscle,” said Chung. “Major proteins in muscles called myosin, actin and titin control the force of each beat. When the heart muscle contracts, myosin binds to actin to generate force. Our lab is trying to determine if motion — and how fast the motion occurs — makes myosin let go of actin faster and make the muscle relax faster.” 
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Wayne State secures more than $5 million in NIH funding for cerebral palsy research

The National Institutes of Health is supporting a Wayne State University School of Medicine physician-researcher’s work at preventing and treating cerebral palsy in the form of two new five-year R01 grants worth a collective $5.59 million. The principal investigator on both projects is Sidhartha Tan, M.D., professor and co-division chief of Neonatology in the Department of Pediatrics. Cerebral palsy is a group of disorders that affect a person’s ability to move and maintain balance and posture. CP is the most common motor disability in childhood, caused by abnormal brain development or damage to the developing brain that affects a person’s ability to control his or her muscles. Tan obtained his first R01 last May for “Potent Neuronal Nitric Oxide Synthase Inhibition for Prevention of Cerebral Palsy,” which will provide $2,393,590 over the half-decade award period to test new, promising drugs aimed at a preventive cure for the condition. “These are new drugs aimed at brain condition called neuronal nitric oxide synthase. New information about how these drugs act, how they affect brain cells and how effective they are in an animal model of cerebral palsy will be very valuable for future translation to clinical use in humans throughout the world,” Tan said. His second, a multiple principal investigator award launched Dec. 15, is “Probing Role of Tetrahydrobiopterin in Cerebral Palsy by Using Transgenic Rabbits.” The grant will provide $3,197,644 in funding over five years to explore whether an essential enzyme co-factor is involved in brain injury before birth. The cellular and genetic basis of brain regional injury will be investigated using an animal model in which genes have been altered by genetic engineering methods, as well as advanced methods of magnetic resonance imaging.
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How Drs. Joseph and Renuka Roche pinpointed a potential treatment for Covid-19

At first, Joseph and Renuka (“Ray”) Roche just followed the news about the coronavirus, like everyone else. After all, they’re not epidemiologists. He is a physical therapist. She is an occupational therapist. So to the Roches, back in January, the novel coronavirus landed somewhere between curiosity and concern. Nearly a year later, the Roches are still a little bit surprised how much of their problem this really is. Because while the nation hinges its hopes on the vaccine news out of companies like Pfizer and Moderna, the Roches came up with a distinctly different approach to the battle against Covid-19. They’ve isolated a potential explanation for the array of symptoms associated with the disease. And they’ve pinpointed an existing drug that could help mitigate these symptoms — but that hardly anyone is talking about. The Roches’ titles are as long as their road to Michigan. Joseph is the Eugene Applebaum College of Pharmacy and Health Sciences Associate Professor of Physical Therapy at Wayne State University. Ray is an assistant professor of occupational therapy (with a focus on developmental neurology) at Eastern Michigan University.
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Wayne State University and Karmanos Cancer Institute to host two-day symposium focused on advancing health equity and the impact of COVID-19

Wayne State University and the Karmanos Cancer Institute will host the “Community-Engaged Research Symposium to Advance Health Equity: The Impact of Coronavirus Now and in the Future,” on Dec. 1 and 2. The virtual symposium is free and open to the public; registration is required and can be completed online. “This is our third annual symposium, and we are honored to take on the challenge of adapting it to the pandemic,” said Rhonda Dailey, M.D., assistant professor of family medicine and public health sciences, and scientific director of the Office of Community Engaged Research at Wayne State University. “The virtual platform is a convenient way for academicians, community organizations and community members involved in community-based research to present their hard-earned work related to COVID-19. We hope that attendees will use the symposium to form new, lasting connections and partnerships.” Community-academic research partnerships are more important than ever, according to Hayley Thompson, Ph.D., professor of oncology in the Wayne State School of Medicine and associate center director for community outreach and engagement at Karmanos Cancer Institute. “Just like cancer, heart disease and a host of other conditions, the burden of COVID-19 is greater in communities of color, in under-resourced areas and among groups who are marginalized in other ways,” said Thompson. “If we want to generate data and knowledge that can make a difference, meaningful collaboration between these groups and academic researchers is essential. This symposium is one step toward real collaboration.”
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This is why you love to be scared

Halloween is almost here which means ghouls, ghosts and goblins will be lurking around every corner, ready to scare you. But have you ever wondered why so many of us love to be scared? Whether it's a scary movie or haunted house, the experts say the thrill and desire of getting creeped out is rooted deep inside your brain. But being able to suspend our disbelief and tap into that primal part of our brain isn't new. "The fear system evolved hundreds of thousands of years ago to prepare us for real dangerous situations," Dr. Arash Javanbakht of Wayne State University said. "Our current environment is too safe so, basically, those fear experiences could also be a form of practice." Javanbakht said constantly asking ourselves "what would I do in that situation?" is a problem-solving exercise to prepare us for similar situations. Experts say that fear can be a great motivator for good. Challenging yourself to face your fears can be a healthy way of proving to yourself that you are capable of things you may not have thought possible.
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The medical community has failed people of color in the past: these doctors want to build trust

The COVID-19 pandemic has swept through the United States, highlighting racial inequities in healthcare. The numbers of infections and deaths related to COVID-19 are far higher among people of color, especially Black Americans, than among white Americans. Despite these higher risks, Black Americans are less likely to sign up for experimental medical treatments or potential vaccines. To help bridge this gap and champion the interests of Black people and other marginalized groups during the pandemic, the National Medical Association set up an expert task force to vet regulators’ decisions about COVID-19 drugs and vaccines. “We are more interested in efficacy,” said Dr. Bret Hughes, a professor of ophthalmology at Wayne State University and longtime member of the National Medical Association. He added that the process for vetting vaccines and other kinds of medications is very regimented and specific, and has two goals: safety first and then effectiveness. But “there are political groups that are willing to bypass those procedures and say there is a vaccine in order to quell fears. In fact, you can take a vaccine and develop other conditions because there’s more in the vaccine no one is aware of until you get it.” Dr. Rick Baker, a professor of ophthalmology and vice dean for medical education at Wayne State University and a longtime National Medical Association member, said the association will be doing three things in vetting vaccines: making sure whatever is developed is scientifically sound and effective; assessing whether there’s adequate representation of people of color in the trials; and ensuring that the distribution of the vaccine is equitable. In these uncertain times, he added, someone needs to be the trusted messenger, adding that physicians are uniquely qualified to be that messenger. “The message needs to be transmitted from physicians to patients,” he said. “The physician-to-patient relationship is very important.”
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Wayne State-led team explores link between diabetes, obesity and liver disease

Diabetes, obesity and nonalcoholic fatty liver disease (NAFLD) are all common diseases that can lead to serious health implications. NAFLD affects over 30% of Americans, and is characterized as a fatty liver, which can progress to an inflammatory and fibrotic liver, called nonalcoholic steatohepatitis (NASH), as well as liver cirrhosis. The molecular causes of NAFLD and NASH are still not fully understood and, to date, no FDA-approved drug is available for NAFLD. A major hurdle for scientists is understanding the causal relationships between NAFLD, diabetes and obesity, which are often presented together in patients and treated as comorbidities. Without a clear understanding of their causal relationship and root cause, drug development may fail. Faculty from Wayne State University’s Eugene Applebaum College of Pharmacy and Health Sciences are leading a team of researchers to understand the causal relationships between these three diseases in hopes of developing a treatment.Wanqing Liu, associate professor of pharmaceutical sciences at Wayne State, along with his collaborators, recently published a paper in the Journal of Hepatology that attempts to understand the molecular causes of NAFLD. The team conducted a large-scale genomic analysis called Mendelian randomization, a strategy similar to a randomized clinical trial that relies on a naturally occurred randomization of genetic alleles in human populations.
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Study explains why fetuses and newborns are mostly spared by COVID-19

Why are newborns born to mothers with COVID-19 rarely infected? Researchers at the Wayne State University School of Medicine and the Perinatology Research Branch of National Institute of Child Health and Human Development/National Institutes of Health in Detroit have found that placental cells minimally express the instructions, or mRNA, to generate the cell entry receptor and protease required by the virus that causes COVID-19 to invade human cells. The pandemic caused by SARS-CoV-2 has infected more than 10 million people worldwide, including pregnant women, yet to date there is no consistent evidence that pregnant mothers pass the virus to their newborns. “The findings of this study help to understand why mother-to-fetus transmission is so rare (less than 2% of cases),” said Roberto Romero, M.D., D.Med.Sci, chief of the PRB. “The most likely explanation is that the cellular instructions for the production of the main receptor for SARS-CoV-2 are not expressed in the human placenta. In contrast, the receptors for other viruses known to cause fetal infection such as Zika and cytomegalovirus were found in placental cells.” Roger Pique-Regi, Ph.D., assistant professor of the WSU Center for Molecular Medicine and Genetics, and of Obstetrics and Gynecology, first author of the study, explained that the single-cell genomics technology the researchers employed allows them to study the transcriptome of individual cells isolated in tiny oil droplets using microfluidics.  
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Addressing the toxicity of cancer treatment costs

Lauren Hamel, Ph.D., assistant professor and member of the Population Studies and Disparities Research Program at Karmanos Cancer Institute and the Wayne State University School of Medicine, was awarded a Research Scholar Grant by the American Cancer Society. She will use the grant to test the effectiveness of a patient-focused intervention to improve patient-provider treatment cost discussions and other patient outcomes related to the financial consequences of cancer treatment. Hamel and her team responded to the growing problem of financial toxicity, or the severe material and psychological burden of the cost of cancer treatment. Financial toxicity affects an estimated 30% to 50% of patients with cancer, especially patients who are racial/ethnic minorities, have lower incomes or are under 65. However, well-timed and effective patient-oncologist treatment cost discussions could help.
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Fireworks can torment veterans and survivors of gun violence with PTSD – here’s how to celebrate with respect for those who served

Arash Javanbakht, associate professor of psychiatry, wrote an article for The Conversation about celebrating the Fourth of July with respect to individuals with PTSD. “For some combat veterans, the Fourth of July is not a time to celebrate the independence of the country they love. Instead, the holiday is a terrifying ordeal. That’s because the noise of fireworks – loud, sudden, and reminiscent of war – rocks their nervous system. Daily fireworks in many U.S. cities in recent weeks have no doubt been interfering with the sleep and peace of mind of thousands of veterans. This reaction is not unique to veterans with post-traumatic stress disorder, or PTSD. Also affected are millions of others, including civilians, refugees, and first responders. As a psychiatrist who specializes in trauma and PTSD, I urge you not to overdo an act which causes so much suffering for so many of your fellow Americans.”
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Why safely reopening high school sports is going to be a lot harder than opening college and pro ball

Tamara Hew-Butler, associate professor of exercise and sports science, and Phillip D. Levy, assistant vice president for translational science and clinical research innovation, wrote an article for The Conversation about reopening school and club sports amidst the pandemic. “Along with the revival of professional sports comes the yearning for a return to amateur sports – high school, college and club. Governing officials are now offering guidance as to when and how to resume play. However, lost in the current conversation is how schools and club sports with limited resources can safely reopen. As an exercise scientist who studies athlete health and an emergency medicine physician who leads Michigan’s COVID-19 mobile testing unit, we wish to empower athletes, coaches and parents by sharing information related to the risks of returning to play without COVID-19 testing. This includes blood tests to see if athletes have already had COVID-19 plus nasal swabs to test for the active SARS-CoV-2 virus. Regular COVID-19 testing on all athletes may seem like overkill, but the current tally of 150 collegiate athletes, mostly football players, who have tested positive for COVID-19 grows longer by the day.”
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Are we all OCD now, with obsessive hand-washing and technology addiction?

David Rosenberg, professor of psychiatry and neuroscience, wrote an article for The Conversation. “One of the hallmarks of obsessive-compulsive disorder is contamination fears and excessive hand-washing. Years ago, a patient with severe OCD came to my office wearing gloves and a mask and refused to sit on any of the “contaminated” chairs. Now, these same behaviors are accepted and even encouraged to keep everyone healthy. This new normal in the face of a deadly pandemic has permeated our culture and will continue to influence it. Many stores now prominently post rules mandating face masks and hand sanitizer use and limit the number of customers allowed inside at one time. Walkers and joggers politely cross the street to avoid proximity to each other. Only a few months ago, this type of behavior would have been considered excessive, irrational, even pathological, and certainly not healthy. So, where do doctors draw the line between vigilance to avoid being infected with the coronavirus and obsessive-compulsive disorder that can be harmful? This is an important question that I, a psychiatrist, and my co-author, a wellness and parenting coach, often hear.”
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Doctors heavily overprescribed antibiotics early in the pandemic

The desperately ill patients who deluged the emergency room at Detroit Medical Center in March and April exhibited the telltale symptoms of the coronavirus: high fevers and infection-riddled lungs that left them gasping for air. With few treatment options, doctors turned to a familiar intervention: broad-spectrum antibiotics, the shot-in-the-dark medications often used against bacterial infections that cannot be immediately identified. They knew antibiotics are not effective against viruses, but they were desperate, and they feared the patients could be vulnerable to life-threatening secondary bacterial infections as well. “During the peak surge, our antibiotic use was off the charts,” said Dr. Teena Chopra, the hospital’s director of epidemiology and antibiotic stewardship, who estimated that more than 80 percent of arriving patients were given antimicrobial drugs. “At one point, we were afraid we would run out.” Chopra and other doctors across the country who liberally dispensed antibiotics in the early weeks of the pandemic said they soon realized their mistake. “Many physicians were inappropriately giving antibiotics because, honestly, they had limited choices,” she said. Chopra estimated that up to a third of coronavirus patients who died at the hospital were killed by opportunistic pathogens like C. difficile, a pernicious infection that causes uncontrolled diarrhea and is increasingly resistant to antibiotics. That figure, she said, was quite likely heightened by the poor underlying health of patients who also had diabetes or hypertension or were obese. “Even before Covid hit, our population in Detroit was very vulnerable to drug-resistant infections,” said Chopra, a professor of infectious diseases at Wayne State University.
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Wayne State University publishes new findings of potentially deadly bacterial infection linked to COVID-19 in older patients

A doctor at Detroit’s Wayne State University School of Medicine has published new findings of a trend in older patients who are severely ill with COVID-19 and also test positive for Clostridioides difficile — a bacteria sometimes referred to C. diff or CDI. The CDI bacteria causes life-threatening diarrhea and is usually a side effect of taking antibiotics, according to the CDC. Wayne State’s observations offer the inaugural CDC journal report of CDI infections in COVID-19 patients. “This is the first report highlighting COVID-19 patients who presented with diarrhea and were found to have both C. diff and diarrhea as a co-infection,” says Dr. Teena Chopra, who is also a professor of infectious diseases at the WSU School of Medicine and corporate medical director of infection prevention hospital epidemiology and antibiotic stewardship at WSU and the Detroit Medical Center. “Most of these patients were very sick and had a higher mortality. COVID-19 can present as diarrhea, and a lot of these patients are getting unnecessary antibiotics. We always think of C. diff when we have patients who have diarrhea, and now we have to think of COVID-19 in these patients, too.”
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Three weeks into Michigan’s coronavirus crisis, the numbers are rising exponentially

It was three weeks ago today that Michiganders woke to the start of the state’s coronavirus crisis. Between Wednesday, March 25, and Tuesday, March 31, the number of completed coronavirus tests for Michigan residents increased from 9,109 to 25,711. Of those 25,711 completed coronavirus tests on Michigan residents, 6,150-- or 24% -- were positive, according to the Michigan Department of Health and Human and Services. It’s unclear how many tests are pending. Some Michigan residents have been pushing for public data on the number of people who have recovered for coronavirus. But it’s too soon to have those numbers, considering the timetable of the epidemic and the timetable of illness and recovery for individual patients, said Dr. Paul Kilgore, a public-health doctor and epidemiologist at Wayne State University. He said that coronavirus symptoms typically last from 10 to 14 days and many are still recuperating “for a couple of weeks afterwards,” he said. “If you’re in the intensive care unit, your recovery is going to be even longer.” Considering the first cases in Michigan were confirmed only three weeks ago, “it’s not all” surprising there is no public data on recoveries from coronavirus, Kilgore said.
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Wayne State team receives $1.98 million NIH award to develop diagnostic tests for sarcoidosis

Sarcoidosis is an inflammatory disease of unknown causes that affects multiple organs in the body. It occurs in patients around the world and is highly prevalent in Detroit and Michigan. It is characterized by abnormal masses or nodules – granuloma formations – in various organs, including lungs and lymph glands, brains and heart. Sarcoidosis has been described for more than 150 years, but there are no specific and simple tests developed to diagnose this disease. A team of researchers led by Lobelia Samavati, M.D., associate professor in the Center for Molecular Medicine and Genetics and Department of Internal Medicine at Wayne State University’s School of Medicine, has been working for more than 10 years to discover specific serological biomarkers of sarcoidosis and tuberculosis. With the help of a recent $1.98-million grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Samavati’s research team aims to advance their work of developing biomarker technology for identification of biomarkers of sarcoidosis. “We believe that our technology will be able to harness the diversity of antibodies and can aid to identify protective antibodies in various diseases in humans, including viral respiratory infections such as the corona virus,” said Samavati. “We believe that this study is the beginning of new era to identify protective immunity in form of antibodies.” Sorin Draghici, the Robert J. Sokol, M.D. Endowed Chair in Systems Biology in Reproduction and professor of computer science in Wayne State’s College of Engineering, is collaborating with Samavati. He contributed to the design of the study and will supervise the data analysis.
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A coronavirus guide for older adults (and their family advocates)

A late February study in the Journal of the American Medical Association showed that children 10 and under accounted for just 1% of all COVID-19 cases, for example, while adults in the 30-79 age groups represented a whopping 87%. The World Health Organization (WHO) found something similar in China, with 78% of patients falling between the ages of 30 and 69. “Older people are more likely to be infected, especially older people with underlying lung disease,” says Dr. Teena Chopra, medical director of infection prevention and hospital epidemiology at Wayne State University. “For this population, mortality rates for COVID-19 are about 15%.” In this sense, COVID-19 behaves a lot like seasonal flu. From 70% to 85% of all flu deaths and 50% to 70% of flu-related hospitalizations occur among people in the 65-plus age group, according to the United States Centers for Disease Control and Prevention (CDC). The 2002-2003 SARS outbreak similarly proved lethal for more than 50% of people over 60 who contracted the disease. “People living in long care facilities have common meetings, they share common rooms,” says Chopra. Common meetings and common rooms can too often mean common pathogens. The health system itself may be playing a significant role in putting seniors at risk. People with multiple medical conditions typically visit multiple specialists, and every such visit means entering a health care environment that can be teeming with viruses and bacteria. For now, Chopra advises older patients to postpone doctor visits that aren’t absolutely essential, like “their annual eye visit. Dental cleaning can be avoided too.” Telemedicine—conducting doctor visits that don’t require hands-on treatment online—can be helpful too, as can e-prescribing, with drugs being delivered straight to patients, sparing them exposure to pharmacies.
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Wayne State researchers receive grant to develop new treatments for Barth syndrome

A team from Wayne State University, led by Miriam Greenberg, Ph.D., professor of biological sciences in the College of Liberal Arts and Sciences, recently received a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health to work on potential new targets for treating Barth syndrome (BTHS). The four-year, nearly $1.5 million award, aims to identify specific metabolites as candidates for new treatments for Barth syndrome and other cardiomyopathies. Barth syndrome is a rare and life-threatening, X-linked genetic disorder that primarily affects males and is passed from mother to son; women who are carriers do not show symptoms of the disorder. Fifty percent of children born to a mother who is a carrier will inherit the defective gene, and all daughters born to an affected man will be carriers. BTHS is caused by a mutation in the tafazzin gene that results in decreased production of cardiolipin, an essential lipid for energy metabolism. According to Greenberg, BTHS causes numerous pathologies, including cardiomyopathy, a disorder of the heart muscle; neutropenia, a reduction in the number of white blood cells; hypotonia, reduced muscle tone; undeveloped skeletal muscles and muscle weakness; delayed growth; decreased stamina; physical disability; and methylglutaconic aciduria, an increase in an organic acid that is characteristic of abnormal mitochondrial function.
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Taking zinc can shorten your cold. Thank a 91-year-old scientist for the discovery

The common cold is a top reason for missed work and school days. Most of us have two or three colds per year, each lasting at least a week. There's no real cure, but studies from the last several years show that some supplement containing zinc can help shorten the duration of cold symptoms by up to 40% — depending on the amount of the mineral in each dose and what it's combined with. Zinc has an interesting back story. It wasn't even acknowledged as an essential mineral for human health until the 1970s. But that changed thanks to the work of Dr. Ananda Prasad — a 91-year-old doctor who, decades ago, had a hunch that led to a better understanding of zinc's role in immunity. Back in the 1960s Prasad was studying a group of young men in Egypt who had not grown to normal heights and remained underdeveloped in other ways, too. Prasad wondered if the problem might be a lack of zinc. When Prasad gave them zinc supplements, the men grew significantly taller. "I couldn't believe it," he says. Prasad had never expected such significant growth. Some scientists challenged his findings, at the time, questioning the idea that zinc deficiency could even occur in humans. "It was controversial," Prasad says. But he pressed on with his research and  began to document the ways zinc influences immunity. Eventually, in the 1970's, the National Academy of Sciences (NAS) declared zinc an essential mineral, fundamental to many aspects of cell metabolism. NAS established a recommended daily allowance, which is the daily amount that's sufficient for good nutrition. Prasad says he felt vindicated by this action. "Absolutely," Prasad told us from his home in Michigan, where he's a researcher and professor at Wayne State University School of Medicine. What came next in his career may be just as surprising. Prasad had demonstrated that zinc had an effect on immunity — so he figured that it might help against a ubiquitous scourge — the common cold.
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Wayne State University launches new Office of Women’s Health

Wayne State University launched its new Office of Women’s Health, a comprehensive approach to improve the health of women overall, through a deep dive into medical research affecting more than half the population of Michigan and the nation, a segment often unintentionally overlooked in research. The Office of Women’s Health marked its official debut with an inaugural symposium Dec. 3 at the university’s McGregor Conference Center that brought together more than 130 researchers from across the university, community and grassroots partnering organizations, and a keynote address from Janine Clayton, M.D. Clayton, the National Institutes of Health’s associate director for Research on Women’s Health and director of the NIH Office of Research on Women’s Health, delivered the address, “Putting Women at Center Stage in Biomedical Research,” the very purpose of the new WSU office. “We have the resources and a wonderful research culture at the university,” WSU President M. Roy Wilson told the attendees. “That, coupled with our concentration on health equity, means we can come together with a focused effort on women’s health.