Announcements

Updates on campus events, policies, construction and more.

close  

Information for Our Community

Whether you are part of our community or are interested in joining us, we welcome you to Washington University School of Medicine.

close  


Amarasinghe elected to American Academy of Microbiology

Gaya K. Amarasinghe, PhD, the Alumni Endowed Professor of Pathology & Immunology and a professor of biochemistry & molecular biophysics and of molecular microbiology at Washington University School of Medicine in St. Louis, has been elected to the American Academy of Microbiology in recognition of his contributions to the field. The academy is an honorific leadership group within the American Society for Microbiology. Amarasinghe is one of 65 fellows hailing from nine countries elected this year.

Amarasinghe’s research centers on how pathogens affect the immune systems of the hosts they infect. By characterizing the molecular mechanisms active in pathogens and hosts during infection, his work can help identify therapeutic targets to tamp down the negative effects of disease development and progression. Amarasinghe’s lab has recently published findings related to Ebola virus, Marburg virus, respiratory syncytial virus and Rift Valley Fever virus as well as bacteria such as Staphylococcus aureus and Mycobacterium tuberculosis, among other pathogens of global concern. Amarasinghe is also committed to mentoring, training undergraduates, graduate students and postdoctoral fellows in a multidisciplinary approach that includes biochemical analyses and biophysical studies.

Researchers find missing link in autoimmune disorder

Autoimmune diseases, which are estimated to affect more than 15 million people in the U.S., occur when the body responds to immune-system false alarms, and infection-fighting first responders are sent out to attack threats that aren’t there. Scientists have long understood how the false alarms get triggered, but the second step of dispatching the immune response has been a mystery.

Now, scientists at Washington University School of Medicine in St. Louis and the Perelman School of Medicine at the University of Pennsylvania have identified a key component to launching immune activity – and overactivity. The researchers identified a protein in cells that spurs the release of infection-fighting molecules. The protein, whose role in the immune system had not previously been suspected, provides a potential target for therapies that could prevent overreactive immune responses that are at the root of several debilitating illnesses.

Their paper was published online Feb. 12 in Cell and will be appear in print March 20.

The team of researchers, co-led by Jonathan Miner, MD, PhD, an associate professor of Rheumatology and Microbiology and a member of Penn’s Colter Center for Autoimmunity, and David Kast, PhD, an assistant professor in the Department of Cell Biology & Physiology at WashU Medicine, made the discovery by studying a rare autoimmune disease called STING-associated vasculopathy with onset in infancy (SAVI). The condition is extremely rare, occurring in one of every 1 million births. It leads to the immune response attacking tissues in the lungs and limbs of patients, often resulting in death before adulthood.

Studying rare diseases where the root cause of the disease is caused by a single mutation can not only reveal the biological role of the affected gene and the disease-causing disruptions it incites, but also provide insight into more-common conditions.

SAVI is caused by changes to a protein in cells called STING, which ordinarily acts as a molecular watchdog that responds to the presence of viral DNA by activating the component of the cell that generates immune proteins. These immune proteins are then released from the cell to signal to the body’s immune system of the need to attack the viral invaders, and where in the body the immune cells need to go. In SAVI, STING is overactive, triggering constant immune activity that ultimately damages healthy tissue.

In addition to signaling the cell to make the immune-response proteins, called cytokines, the researchers discovered that STING also has a novel role in releasing those proteins from where they are made in the cell. How that release process worked was unknown, but finding a way to control it could be a promising avenue for treating SAVI as well as other autoimmune disorders.

Using immune cells that were sensitive to the disease-causing mutations in STING, the team performed a screen to identify proteins that prevented this sensitivity. One protein, ArfGAP2, stood out, as it seemed to be strongly connected to the final step when the immune response proteins get released.

The team further validated this finding in SAVI cells that did not produce ArfGAP2. Without it, STING could not drive the release the immune proteins.

“It’s like a train station and ArfGAP2 is acting as the conductor, directing which molecules are to be shipped out,” said Kast. “If STING and ArfGAP2 are not working together, the trains are stopped.”

The team reasoned that stopping the never-ending “trains” in SAVI’s constant immune response could be a means of treating the rare disease.

The team tested that idea in a mouse that was genetically modified to have SAVI, but did not produce the ArfGAP2 protein. They found that the lung- and limb-destroying immune response typical of the disease did not occur, which confirmed that if the protein could be neutralized, the overactive immune response could be turned off.

Miner, who initiated the project when he was at WashU Medicine, said that it is a promising target for other conditions that similarly lead to excess immune proteins of the same type. This could include the “cytokine storms” characteristic of COVID-19 or the brain inflammation linked to immune responses in Alzheimer’s disease.

“Diseases like SAVI that are super rare can provide valuable insights,” said Miner, “because if you can figure out how a rare disease mutation is working, you learn something about the normal proteins that all of us have. Then suddenly you’ve opened the doors to all these new avenues of potential therapies for many, many different classes of diseases.”

Obituary: William D. Owens, MD, professor emeritus of anesthesiology, 85

William D. Owens, MD, a highly regarded professor emeritus of anesthesiology and former head of the Department of Anesthesiology at Washington University School of Medicine in St. Louis, died of cancer on Friday, Jan. 3, 2025, while in hospice care at Evelyn’s House in Creve Coeur, Mo. He was 85.

“Dr. Owens shaped the field of anesthesiology through his clinical expertise, teaching and research in clinical outcomes,” said Michael S. Avidan, MBBCh, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology and head of the Department of Anesthesiology at WashU Medicine. “He was a beloved mentor and educator.”

Born in Gerald, Mo., in 1939, Owens received his medical degree from the University of Michigan in 1965. After serving with distinction in the U.S. Navy, he completed residency training at Massachusetts General Hospital and joined the faculty at Harvard Medical School.

Owens joined Washington University in 1973 and rose to full professor in 1981. He served as head of the Department of Anesthesiology and anesthesiologist-in-chief at Barnes Hospital and St. Louis Children’s Hospital from 1982 to 1992. He retired from the university as an emeritus professor in 2004.

As department head, he is credited with expanding and strengthening clinical care and professional training, launching basic and clinical research programs and establishing the anesthesiology critical care and pain management programs at WashU Medicine.

A pioneer in clinical outcomes research and a champion of anesthesia education, his work continues to influence anesthesiology practices worldwide. He held national leadership roles with the American Society of Anesthesiology, the American Board of Anesthesiology, the Academy of Anesthesiology, the Foundation of Anesthesia Education and Research and the World Federation of Societies of Anesthesiologists.

Owens also authored “History of Anesthesiology and the Department of Anesthesiology, Washington University in Saint Louis School of Medicine and Barnes Hospital, 1912–1992,” chronicling the department’s rich history and its contributions to the field.

He is survived by his wife, Patricia, of 60 years; his brother Robert; three children who are all graduates of WashU, Pamela (AB ’88), David (MD ’98) and Susan (MPT ’95); and seven grandchildren.

Memorial contributions may be made to the William D. Owens Anesthesiology Research Fellowship at Washington University School of Medicine.

To read more about his life, see here.

Female sex hormone protects against opioid misuse, rat study finds

The opioid epidemic has claimed more than half a million lives in the U.S. since 1999, about three-quarters of them men, according to the National Institutes of Health. Although men’s disproportionate rates of opioid abuse and overdose deaths are well-documented, the reasons for this gender disparity are not well understood.

A new study in rats by researchers at Washington University School of Medicine in St. Louis suggests that one underlying cause may be biological. Male rats in chronic pain gave themselves increasing doses of an opioid – specifically, fentanyl – over time, while female rats with the same pain condition kept their intake at a constant level, similar to what is seen in people. The behavioral difference was driven by sex hormones, the researchers found: treating male rats with the hormone estrogen led to them maintain a steady level of fentanyl intake.

The findings, published March 10 in the journal Neuron, indicate that differences in how men and women use and misuse opioids may be driven by their hormones, and that a deeper understanding of how sex hormones interact with chronic pain could open up new approaches to addressing the opioid epidemic.

“These data suggest that men may be inherently predisposed to misuse opioids in the context of pain because of their balance of sex hormones,” said lead author Jessica Higginbotham, PhD, a postdoctoral researcher in the lab of Jose Moron-Concepcion, PhD, the Henry Elliot Mallinckrodt Professor of Anesthesiology at WashU Medicine and the paper’s senior author. “We focused on estrogen in this study, but I doubt the effect we saw is due to estrogen alone. It is more likely to be the balance of all the sex hormones in the body that influences risk. Men and women have the same sex hormones, just in different amounts, and our data suggest that females have a more protective balance than males. But if that balance changes, the risk of developing opioid use disorder could change, too.”

Pain’s influence on pleasure from opioids

Most people who misuse opioids take the drugs to relieve pain, but men are more likely to overdose on opioids than women are, even though they suffer less chronic pain, according to data from national surveys. Scientists hypothesize that something other than, or in addition to, chronic pain must be putting men at higher risk of developing problems managing their opioid use.

When a person – or a rat – takes an opioid such as fentanyl, it acts on the brain in two ways. The drug blocks the transmission of pain signals, relieving pain, and it triggers the release of dopamine from the reward center in the brain, creating a feeling of euphoria. Previous work by Moron-Concepcion and members of his laboratory had shown that pain itself affects dopamine levels in the brain, suggesting that opioids and pain may interact to influence dopamine levels.

To understand how pain influences opioid-seeking behavior in sex-specific ways, Higginbotham and Moron-Concepcion studied rats with chronic pain in their paws. They found no difference between males and females in terms of how much pain the animals experienced, as measured by how quickly they drew back their paws when touched. They also found no difference between the sexes in how much pain relief a dose of fentanyl provided, using the same measurement. And yet the males went back for more and more fentanyl over the course of the three-week study, while the females did not.

The researchers discovered an important difference between male and female rats in the amount of dopamine released after a dose of fentanyl. Females produced the same amount of dopamine from fentanyl over the course of the experiment, regardless of whether they were in pain or not. Males that were not in pain responded like females. In contrast, males in chronic pain generated a bigger and bigger dopamine response to fentanyl over time. In other words, pain made the feel-good part of opioids feel even better for males, but not for females.

“We had thought that maybe the males developed a tolerance to fentanyl and needed increasing amounts to relieve the pain, but that wasn’t it,” said Moron-Concepcion, also a professor of psychiatry and of neuroscience. “The males were taking more and more fentanyl to feel that ever-increasing high. In males, but not females, the pain condition itself affected the reward centers of the brain and drove them to take more drugs.”

Estrogen reduces fentanyl use

Further experiments revealed that sex hormones were responsible for the different dopamine responses in male and female rats.

Ovaries are the primary source of sex hormones in females, producing estrogen, progesterone and small amounts of testosterone. The researchers found that female rats whose ovaries had been removed responded to fentanyl like males did, with increasing amounts of dopamine released and an increase in opioid-seeking behavior. In contrast, males that were given estrogen had dopamine responses and opioid-seeking behavior similar to females.  The findings suggest that a drop in estrogen levels with menopause may help explain why older women have higher rates of opioid abuse compared to younger women, Higginbotham said.

“What we can do now is start thinking about how to find the right balance of hormones to prevent opioid use disorder in people with chronic pain,” Moron-Concepcion said. “We haven’t yet looked at the role of other sex hormones such as testosterone or progesterone. Is there a perfect combination of hormones that can reverse the effects of pain on opioid use? That’s something we’d like to find out.”

$4.5 million supports pathbreaking neuroimmunology research

Washington University School of Medicine in St. Louis has received a three-year, $4.5 million grant from the Carol and Gene Ludwig Family Foundation, aimed at advancing research on neuroimmunology and neurodegeneration with the ultimate goal of developing new treatments for Alzheimer’s disease. Administered by WashU Medicine’s Brain Immunology & Glia (BIG) Center, the Carol and Gene Ludwig Initiative in Neuroimmunology Research will support innovative projects led by David M. Holtzman, MD; Jonathan Kipnis, PhD; and Marco Colonna, MD, in addition to other faculty members through a seed grant program.

“This award recognizes exceptionally exciting and innovative work in the area of neuroimmunology at WashU Medicine,” said David H. Perlmutter, MD, the George and Carol Bauer Dean of WashU Medicine, executive vice chancellor for medical affairs and the Spencer T. and Ann W. Olin Distinguished Professor. “This support from the Ludwig Foundation will help to accelerate advances in understanding the interplay between the brain and the immune system and harness that knowledge to identify novel targets for treatment of Alzheimer’s disease and possibly even prevention of dementia. This work is among the finest examples of the secret sauce of collaboration at WashU that brings together physicians and scientists from different disciplines to achieve more than they could individually.”

Holtzman, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology, contributed to understanding the role for the immune system in Alzheimer’s disease, in work published in Nature in 2023. The brain’s resident immune cells – microglia – had been previously implicated in causing injury to brain tissue. The Holtzman laboratory found that microglia interact with another immune cell type — T cells — enabling them to both enter the brain and contribute to neurodegeneration in a mouse model. Their work demonstrated that removing T cells from the brain prevents brain damage and cognitive impairment.

The Carol and Gene Ludwig Initiative in Neuroimmunology Research will support an in-depth study of the processes responsible for activating and recruiting a subset of harmful T cells to the brain to cause disease.

“We know the imbalanced immune response could be involved in causing neurodegenerative disease,” said Holtzman. “A complete picture of the immune players and their interactions will help us identify and test therapeutic targets to interfere with the progression of neurodegeneration.”

Colonna, the Robert Rock Belliveau, MD, Professor of Pathology, in collaboration with the Holtzman lab, will explore innovative therapies that enhance microglia’s ability to engulf amyloid protein plaques that accumulate in the brains of Alzheimer’s patients. In research published in Science Translational Medicine, Colonna and Holtzman previously found that mobilizing microglia by lifting their natural brakes is a promising strategy for removing the noxious plaques that build up and cause cognitive decline in Alzheimer’s. With the funding, they can advance this approach toward therapeutic testing.

Kipnis, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator, studies the interactions between the immune system and the central nervous system. Studies in his lab published in Nature have shown that the drainage system in the brain physically connects the immune system with the central nervous system, opening opportunities to study the neuroimmune interactions during the course of disease and in good health. The new award will support Kipnis’ endeavors to engineer immune cells to prevent or halt neurodegeneration in mouse models of Alzheimer’s.

“These studies have the potential to transform the treatment of Alzheimer’s,” said Kipnis, the inaugural director of the BIG Center. “We aim to develop Alzheimer’s immunotherapies that can be tailored to individual patients, while also expanding this work into other age-associated central nervous system disorders.”

The initiative also will fund seed grants – the Carol and Gene Ludwig Awards for Neuroimmunology Research – that will be administered by the BIG Center’s leadership team. Two applicants will be selected each year for three years, with $200,000 distributed each year.

The Carol and Gene Ludwig Family Foundation previously provided grant funding to WashU Medicine, including support for Holtzman and Kipnis. The charitable, private foundation, established in 2002, invests in organizations that accelerate medical and scientific discovery, enable access to educational and economic opportunities for young people, and enrich and strengthen communities.

“We hope our support helps propel advances in neurodegenerative research,” said Carol Ludwig, co-founder and president of the Carol and Gene Ludwig Family Foundation. “The outstanding work of Drs. Holtzman, Kipnis and Colonna, along with the depth of expertise at WashU Medicine, creates an extraordinary environment for advancing research and cultivating talent in this field.”

Two WashU Medicine projects compete in STAT Madness tournament

Editor’s note: On March 10, the two WashU Medicine projects advanced to the second round of the STAT Madness competition. The first WashU Medicine team is now up against UW Medicine; the second team is competing with the Broad Institute of MIT and Harvard / Whitehead Institute. The second round of voting closes at 4 a.m. ET Saturday, March 15. 

For people who may not follow college basketball but want to share in the March tradition of cheering for a team as it tears through a tournament bracket, Washington University School of Medicine in St. Louis has come through for you. STAT, an online publication focused on medicine, health and scientific discovery, has included two WashU Medicine projects in their annual STAT Madness competition, an elimination-style tournament to select the top biomedical innovation or discovery of the previous year.

Aspiring biomedical bracketologists can see – and vote – for all entrants on the STAT Madness website. The winner of each round is determined by popular vote, and fans can vote once per day. First round voting closes at 4 a.m. ET Monday, March 10, and is open to everyone to participate and vote daily.

The WashU Medicine research team led by neurology professor Nico U. F. Dosenbach, MD, PhD, and Ginger E. Nicol, MD, an associate professor of psychiatry, was selected for its discovery that the psychedelic compound psilocybin, found in magic mushrooms, disrupts a specific region of the brain called the default mode network. The team used intensive MRI scanning on volunteer subjects to measure brain activity before, during and weeks after a controlled administration of psilocybin. The default network – a connected series of brain regions that synchronize their activity when the mind is not focused on another task – was significantly desynchronized during the acute phase of the psilocybin trip, with lingering effects for weeks afterwards.

Psilocybin is believed to have potential as a medication to combat conditions such as depression or post-traumatic distress, and this research is an important step to better understand what it is doing in the brain, and how those effects could have therapeutic value.

In the first round of the bracket, Dosenbach and his colleagues are pitted against a research team from UC Davis.

The second WashU Medicine team was chosen for a phase 1 clinical trial of a cancer vaccine conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine. The study shows promising results for patients with triple-negative breast cancer who received an investigational vaccine designed to prevent recurrence of tumors.

The neoantigen DNA vaccine, developed by a team led by William E. Gillanders, MD, the Mary Culver Distinguished Professor of Surgery, used proteins produced by a patient’s own tumor to train their body’s immune system to attack cells with those proteins. The aggressive triple-negative breast cancer has no other targeted treatment and has a high risk of coming back even if removed surgically. Although the clinical trial was only designed to test the safety of the procedure, 16 of the 18 participants had no recurrence of their cancer even after three years, whereas the average for this form of cancer is 50%.

The Gillanders team is pitted against a group from the Wyss Institute at Harvard University and the Dana-Farber Cancer Institute.

The schedule of voting for each round is as follows:
·      First round: Ends at 4 a.m. ET Monday, March 10.
·      Second round: Ends at 4 a.m. ET Saturday, March 15.
·      Third round: Ends at 4 a.m. ET Thursday, March 20.
·      Fourth round: Ends at 4 a.m. ET Thursday, March 27.
·      Semi-finals: Ends at 4 a.m. ET Wednesday, April 2.
·      Finals: Ends at 9 p.m. ET. Sunday, April 6.

Compound harnesses cannabis’ pain-relieving properties without side effects

Treatment for chronic pain still relies heavily on opioids. While effective, they are highly addictive and potentially deadly if misused. In the quest to develop a safe, effective alternative to opioids, researchers at Washington University School of Medicine in St. Louis and Stanford University have developed a compound that mimics a natural molecule found in the cannabis plant, harnessing its pain-relieving properties without causing addiction or mind-altering side effects in mice.

While more studies are needed, the compound shows promise as a nonaddictive pain reliever that could help the estimated 50 million people in the U.S. who suffer from chronic pain. The study is published March 5 in Nature.

“There is an urgent need to develop nonaddictive treatments for chronic pain, and that’s been a major focus of my lab for the past 15 years,” said the study’s senior author Susruta Majumdar, PhD, a professor of anesthesiology at WashU Medicine. “The custom-designed compound we created attaches to pain-reducing receptors in the body but by design, it can’t reach the brain. This means the compound avoids psychoactive side effects such as mood changes and isn’t addictive because it doesn’t act on the brain’s reward center.”

Opioids dull the sensation of pain in the brain and hijack the brain’s reward system, triggering the release of dopamine and feelings of pleasure, which make the drugs so addictive. Despite widespread public health warnings and media attention focused on the dangers of opioid addiction, numerous overdose deaths still occur. In 2022, some 82,000 deaths in the U.S. were linked to opioids. That’s why scientists are working so hard to develop alternative treatments for pain.

“For millennia, people have turned to marijuana as a treatment for pain,” explained co-corresponding author Robert W. Gereau, PhD, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology and director of the WashU Medicine Pain Center. “Clinical trials also have evaluated whether cannabis provides long-term pain relief. But inevitably the psychoactive side effects of cannabis have been problematic, preventing cannabis from being considered as a viable treatment option for pain. However, we were able to overcome that issue.”

The mind-altering properties of marijuana stem from natural molecules found in the cannabis plant referred to as cannabinoid molecules. They bind to a receptor, called cannabinoid receptor one (CB1), on the surface of brain cells and on pain-sensing nerve cells throughout the body.

Working with collaborators at Stanford University, co-first author Vipin Rangari, PhD, a WashU Medicine postdoctoral research associate in Majumdar’s laboratory, designed a cannabinoid molecule with a positive charge, preventing it from crossing the blood-brain barrier into the brain while allowing the molecule to engage CB1 receptors elsewhere in the body. By modifying the molecule such that it only binds to pain-sensing nerve cells outside of the brain, the researchers achieved pain relief without mind-altering side effects.

They tested the modified synthetic cannabinoid compound in mouse models of nerve-injury pain and migraine headaches, measuring hypersensitivity to touch as a proxy for pain. Applying a normally non-painful stimulus allows researchers to indirectly assess pain in mice. In both mouse models, injections of the modified compound eliminated touch hypersensitivity.

For many pain relievers, particularly opioids, tolerance to the medications over time can limit their long-term effectiveness and require higher doses of medication to achieve the same level of pain relief. In this study, the modified compound offered prolonged pain relief – the animals showed no signs of developing tolerance despite twice-daily treatments with the compound over the course of nine days. This is a promising sign that the molecule could be used as a nonaddictive drug for relief of chronic pain, which requires continued treatment over time.

Eliminating the compound’s tolerance resulted from the bespoke design of the compound. The Stanford collaborators performed sophisticated computational modeling that revealed a hidden pocket on the CB1 receptor that could serve as an additional binding site. The hidden pocket, confirmed by structural models, leads to reduced cellular activity related to developing tolerance compared to the conventional binding site, but it had been considered inaccessible to cannabinoids. The researchers found that the pocket opens for short periods of time, allowing the modified cannabinoid compound to bind, thus minimizing tolerance.

Designing molecules that relieve pain with minimal side effects is challenging to accomplish, said Majumdar. The researchers plan to further develop the compound into an oral drug that could be evaluated in clinical trials.

Undiagnosed diseases clinic expands outreach to underserved communities

For people living with rare and puzzling medical symptoms, getting a diagnosis is often a long and frustrating process punctuated by many tests and few results. The Washington University School of Medicine in St. Louis Undiagnosed Diseases Network (UDN) Diagnostic Center of Excellence was established in 2019 to solve the trickiest medical mysteries in Missouri and nearby states. It is one of 11 sites in the national UDN funded by the National Institutes of Health (NIH). In the past five years, the center’s team of WashU Medicine geneticists, bioinformaticians, and pediatric and adult medicine specialists have taken on 189 such cases and cracked 56 of them, a success rate on par with the national network.

Now, the center is expanding. Buoyed by the renewal of the center’s five-year, $3.8 million grant, the UDN leadership team plans to increase outreach to medically underserved communities and increase capacity from 30 to 50 patients a year. The center has established a collaboration with the St. Louis Integrated Health Network, an organization dedicated to improving the quality, accessibility and affordability of health care. Together, they will work to identify people with mysterious illnesses in underserved communities who could benefit from its advanced diagnostic capabilities and help them access its services.

Because most rare, mysterious illnesses have a genetic component, genetic testing is a key part of the approach at the UDN, along with a thorough clinical evaluation by WashU Medicine pediatricians and other clinicians with expertise in rare diseases. Sometimes, a genetic change is found with unclear significance. In those cases, UDN researchers use simple organisms — specifically, nematode worms (C. elegans) and zebrafish — to study the effects of the genetic change, and ascertain whether it is likely to be the cause of the patient’s symptoms.

Learn about the new Center for Rare, Undiagnosed and Genetic Diseases at WashU Medicine »

Each case is unique and complex, and can take months to years to solve. Obtaining a diagnosis can be critical for guiding care decisions, establishing eligibility for precision medicine therapies and clinical trials, and connecting patients and their families with communities of people living with the same condition. Sometimes the diagnostic odyssey ends without a diagnosis. Those cases are frustrating and disappointing to patients and doctors alike, but at least the patient and his or her family know that everything possible has been done to get them an answer.

Breaking down barriers to genetic testing

An estimated 3 million people in the U.S. live with undiagnosed diseases, defined as medical conditions without a known cause despite extensive efforts to find one. Members of medically underserved communities — typically high-poverty areas where primary care providers are in short supply and access to medical care is limited — find it particularly hard to get a diagnosis.

One reason is that most undiagnosed diseases turn out to be genetic in origin. Genetic testing can be expensive – ranging from a few hundred dollars to over $5,000, depending on the specific test – and it isn’t always covered by insurance. Studies have shown that people who are uninsured or underinsured have less access to genetic testing.

“A patient’s insurance status is one factor that can impact whether they are referred for and receive genetic testing,” said Brett Maricque, PhD, an assistant professor of genetics at WashU Medicine and the leader of the center’s community engagement team. “Where they get their care also matters. Community health clinics have few financial resources to pay for genetic testing. That’s why we’re focused on expanding access to cutting-edge diagnostics, including to those that are underinsured or uninsured.”

Studies also have shown that genetic diseases are less likely to be identified and accurately diagnosed in people of color. This is partly because genetic test results are compared against reference databases to identify the significance of the results. These databases are mostly composed of people of European descent, which means that people of other ancestral backgrounds are more likely to receive inconclusive results.

With such issues in mind — as well as a nudge from the national UDN — director Patricia Dickson, MD, the Centennial Professor of Pediatrics and a professor of genetics at WashU Medicine, assessed the demographics of the center’s patient population.

“We take on the hardest-to-solve cases,” Dickson said. “These are people who have spent years fruitlessly searching for a diagnosis. Admittedly, we don’t always solve them. But everyone deserves the chance to get an answer. It shouldn’t be limited by who you are, where you live or how much money you have.”

Patricia Dickson, MDHuy Mach
Patricia Dickson, MD, the Centennial Professor of Pediatrics and a professor of genetics at WashU Medicine, studies rare genetic diseases called lysosomal storage disorders. She is the director of WashU Medicine’s Undiagnosed Diseases Network (UDN) Diagnostic Center of Excellence.

The assessment revealed that the proportion of rural residents among the center’s patients matched that of the areas the center serves, but the racial, ethnic and income proportions did not. Black and Hispanic patients and those with lower incomes were underrepresented among the center’s patients.

It was Maricque who suggested collaborating with the Integrated Health Network to address the disparities in the patient population. The Integrated Health Network coordinates the four Federally Qualified Health Centers in the St. Louis area, which are government-funded nonprofit clinics that provide primary care services in underserved areas.

“Our whole purpose is to help expand health-care access for people in underserved communities,” said Brittany Jones, the assistant director of clinical and community services and racial equity initiatives at the Integrated Health Network. “For many people, it can be difficult to navigate the health-care system just to get a physical, vaccination or prescriptions, and it’s even more difficult when they have a rare condition that they don’t understand. Many people don’t know what undiagnosed diseases are, or don’t have  a pathway to getting a diagnosis. They may not know how to describe their symptoms in a way that providers understand, and providers do not always provide time and space to listen to patients’ needs, concerns or goals. Our role is to bridge that gap so everyone can get the care that they need and deserve.”

Part of the center’s renewal grant will go toward supporting a full-time staff member at the Integrated Health Network dedicated to helping people with undiagnosed diseases access care. This person will raise public awareness of undiagnosed diseases, help health-care providers improve their communication skills to reduce miscommunication, and facilitate referrals to the WashU Medicine UDN center.

“The goal is to get to where our participant demographics match our region’s demographics, not by turning anyone away, but by doing a better job of finding people who can benefit from our services in communities we’re not currently reaching very well,” Dickson said. “We are fortunate to have a partner in the Integrated Health Network that knows how to sensitively approach communities and engage with them. I’m excited to partner with them and bring this program more fully into the St. Louis community.”

WashU Medicine’s pioneering diagnostics and therapeutics for cancer care

WashU Medicine launches center for rare diseases

Washington University School of Medicine in St. Louis has launched the Center for Rare, Undiagnosed and Genetic Diseases, supported by an $8.5 million grant from Children’s Discovery Institute (CDI), a partnership with St. Louis Children’s Hospital, St. Louis Children’s Hospital Foundation and WashU Medicine. The new center brings together WashU Medicine researchers and the rare disease patient community, creating a collaborative network to drive innovative research and accelerate drug discovery.

“The St. Louis area has a robust rare disease patient population,” said Patricia Dickson, MD, the Centennial Professor of Pediatrics and a professor of genetics at WashU Medicine and the new center’s director. “WashU Medicine has the resources that enable cutting-edge rare disease research. But the two have not connected well. The patient-facing center fosters that connection, helping to deliver more diagnoses and create therapies for rare disease patients.”

Patients in Missouri and surrounding states with unexplained symptoms who have exhausted their community’s diagnostic resources often turn to WashU Medicine for answers. With support from the NIH, the Undiagnosed Diseases Network (UDN) Diagnostic Center of Excellence helps patients who, despite extensive medical evaluation, remain undiagnosed. WashU Medicine joined the network in 2018 and is among 15 clinical sites nationwide with the resources to help solve the toughest cases. Washington University and BJC Healthcare are also a founding center of excellence site for the National Organization for Rare Disorders. Such sites are dedicated to advancing care for patients with rare disease.

In-house genetic diagnostic testing recently launched by the Clinical Genomics Laboratory, a collaboration between the Departments of Pathology & Immunology and Genetics, can rapidly identify genetic variations that may be linked to a patient’s medical condition. Through WashU Medicine’s model organism screening center, co-led by Stephen Pak, PhD, a professor of pediatrics, and Tim Schedl, PhD, a professor of genetics, researchers can then insert those genetic variations into model organisms in the lab to probe their functions and observe whether they lead to conditions similar to those in the patients. The new rare disease center will provide additional funding to support UDN’s expansion of its diagnostic capabilities, helping even more patients whose cases remain unsolved.

Beyond diagnosis, the center also aims to help patients with rare diseases for which there are no treatments. Established resources in WashU Medicine’s clinical research units are partnering with the center to help investigators pursue clinical trials for rare disease. Educational workshops will train researchers in clinical research design, reducing barriers to bringing therapies for rare disease to the clinic.

“The center addresses our gap in translational studies for rare disease,” said Dickson. “Rare disease clinical trials are very different from larger, more-common disease clinical trials. Small patient populations, young participants and invasive therapies are just some of the hurdles that researchers may have to address when designing studies. Creating educational opportunities and a robust infrastructure for translational studies will help researchers overcome such challenges.”

Rare disease clinical trials depend on patients and researchers collaborating. By creating opportunities for WashU Medicine’s rare disease experts and affected families to come together, the center fosters an interconnected ecosystem to help improve genetic diagnostic testing, implement genetic newborn screening, support clinical trials for rare disease therapies and bring new treatments into the clinic.

The new center amplifies a collaborative exchange that is already happening between WashU Medicine researchers and family-founded advocacy groups. Such groups provide essential pilot funds that enable WashU Medicine researchers to secure additional support from larger funders to study and develop diagnostics or therapeutics, Dickson explained. They also help investigators understand patients’ needs to tailor research goals appropriately. More recently, such collaborations have helped create research clinics, which collect data from rare disease patients when they travel from all over the world to seek help from WashU Medicine’s experts. The center will fund such clinics – often lacking stable funding – to facilitate the data collection essential for enhancing the understanding of rare conditions and ultimately develop therapeutics.

The center also supports the annual Rare Disease Day Symposium in February. Now in its third year, the event brings together more than 200 participants, including researchers, patient- and parent- advocates and representatives from rare disease therapeutic companies, to network and learn about rare disease research advances and medical innovations happening at WashU.

“This new center strengthens connections among our vast rare disease research and clinical communities and solidifies collaborations with patients to advance diagnosis and treatment of rare, undiagnosed and genetic disease,” said Gary Silverman, MD, PhD, the Harriet B. Spoehrer Professor of Pediatrics, head of the Department of Pediatrics and executive director of CDI. “It represents a community working together on a shared mission to help patients with often overlooked conditions.”

Study highlights barriers to genetic testing for Black children

Studies have shown that Black children with serious illnesses are less likely than white children to obtain crucial genetic testing necessary to guide treatment decisions, but the reasons for this disparity have not been fully understood. A new study from Washington University School of Medicine in St. Louis focused on children with neurological conditions finds that only 50% of Black patients completed genetic testing within a year of doctors referring patients for such testing, compared with 75% of white patients. The results indicate the disparity is due to differences in the type of health insurance kids have and other barriers to accessing care.

The findings, published Feb. 12 in the journal Neurology, highlight the difficulties that patients — particularly Black patients — face in accessing genetic testing to receive accurate diagnoses, the researchers said. The results are already changing practice at WashU Medicine’s pediatric neurology clinic, where a genetic counselor has been embedded to help address some of the access challenges uncovered by the study.

“For children with neurological conditions, genetic testing is essential to obtaining a diagnosis and guiding treatment decisions. If a physician refers a patient for genetic testing, and the patient is unable to get such testing, that really limits the care that physician can provide,” said co-senior author Christina Gurnett, MD, PhD, the A. Ernest and Jane G. Stein Professor of Developmental Neurology and the director of the Division of Pediatric and Developmental Neurology at WashU Medicine. Gurnett is a pediatric neurologist who sees patients at St. Louis Children’s Hospital. “Having genetic information about a patient’s illness determines which medicine we choose. It determines how we monitor for associated conditions, and what we tell families about what they can expect for their child. Disparities in accessing testing translate into inequities in health.”

Genetic testing is recommended for all children with epilepsy or unexplained global developmental delay/intellectual disability, as well as some children with other neurological conditions. Identifying the specific genetic alteration responsible for a child’s symptoms is critical for guiding care decisions, establishing eligibility for precision medicine therapies and clinical trials, and connecting patients and their families with communities of people living with the same condition. Because many genetic conditions are inherited, having precise information can also help parents understand the risks that any future children will inherit such conditions.

Obtaining a genetic test is not a quick or simple process. It can also be expensive, ranging from a few hundred dollars to more than $5,000, depending on the specific test ordered. The child’s doctor must first recognize that genetic testing is indicated and submit a request for approval to their health insurance company. Next, the health insurance company must review the request and provide authorization for the test. Caregivers then typically need to schedule one or more appointments to actually receive the testing.

Gurnett — along with co-senior author Joyce Balls-Berry, PhD, an associate professor of neurology, and first author Jordan Cole, MD, then a neurogenetics fellow at WashU Medicine — collaborated with WashU’s Center for the Study of Race, Ethnicity and Equity to design a study to investigate genetic testing disparities in pediatric neurology and identify ways to address them.

WashU Medicine is a major provider of specialty pediatric neurology care, with patients traveling from throughout the region and surrounding states for care. The researchers examined the records of all 11,371 outpatients seen by WashU Medicine pediatric neurologists between July 2018 and January 2020. They compared genetic testing requests, insurance denials and test completion rates for 1,718 non-Hispanic Black and 8,883 non-Hispanic white patients. (The numbers of patients from other ethnic or racial groups were too small for reliable statistical analysis.) The researchers also gathered data on diagnoses, the type of genetic test ordered, insurance type (public or private), neighborhood social disadvantage and other factors that may influence access to testing.

Black and white children were equally likely to be referred for genetic testing by their neurologist (3.4% of all patients in both groups), but white children were one-and-a-half times as likely as Black children to have received at least one genetic test within a year of the referral. When the researchers controlled for influences such as age, socioeconomic status, number of visits and diagnoses, the disparity widened and white patients were nearly twice as likely to receive genetic testing as were Black patients.

A bar graph showing the completion rates for genetic testing for Black and white children.Sara Moser
Only half of Black children obtained genetic testing ordered by their neurologists, compared to three-quarters of white children, according to a study by researchers at WashU Medicine. Among all patients, nearly 30% of genetic testing orders remained unfulfilled within a year. WashU Medicine’s pediatric neurologic clinic has added a staff person to address barriers to access.

This disparity was partially due to insurance denials. For both private and public insurance, there was no racial disparity in denial rates. However, more Black children in the study had public insurance, and public insurance was more likely to deny requests for genetic testing. Children with public insurance – regardless of race – were 41% less likely to complete genetic testing requested by a neurologist than were children with private insurance.

Even after accounting for the difference in insurance, Black families faced additional challenges in accessing genetic testing for their children. More than a quarter (27%) of Black patients were unable to get genetic testing for reasons other than insurance denials, as opposed to 15% of white patients. Other factors, such as traveling for multiple appointments, may have also contributed to the difficulties families faced getting genetic testing for their children.

“Our health-care providers are asking for genetic testing for our patients; the disparity is happening once the families try to access testing,” Balls-Berry said. “We don’t know where this is coming from. There are factors we were not able to measure.”

The racial disparities accompany what is already challenging for families of all backgrounds. Among all pediatric neurology patients who were referred for genetic testing, nearly 30% of genetic testing orders remained unfulfilled within a year. To lower the barriers to testing for patients, the WashU Medicine pediatric neurology clinic hired a genetic counselor to address the specific roadblocks uncovered by the study. Trained in communication as well as in clinical genetics, the counselor can answer questions, guide families through the process of obtaining testing and serve as a bridge between families and insurance companies.

“It’s really important that we don’t let genetic testing become something that only well-resourced people have access to,” Cole said. Now an assistant professor at the University of Colorado Anschutz Medical Campus and a pediatric neurologist at Children’s Hospital Colorado, Cole has a larger follow-up study underway with colleagues at WashU Medicine and the University of Colorado. “Our research showed that one of the biggest factors associated with who got genetic testing was race. That is unacceptable. We need to understand better why this is happening so we can address it and ensure that everyone who needs genetic testing has access.”

Ahmad, Fraum named Loeb Teaching Fellows

Fahd A. Ahmad, MD, an associate professor of pediatrics, and Tyler Fraum, MD, an associate professor of radiology, have been named the 2025-27 Carol B. and Jerome T. Loeb Teaching Fellows at Washington University School of Medicine in St. Louis.

The two-year fellowship provides recipients extra time to focus on implementing innovative ideas to enhance the education of medical students and residents. The program was established in 2004 with a gift from Carol B. and Jerome T. Loeb to advance medical education.

“For decades, the Loebs’ generosity has fostered innovation and excellence in our curriculum and demonstrated a steadfast commitment to educating the next generation of physicians and physician-scientists,” said Eva Aagaard, MD, vice chancellor for medical education, senior associate dean for education, and the Carol B. and Jerome T. Loeb Professor of Medical Education at WashU Medicine. “Their dedication is reflected in our students, trainees and alumni who emphasize a holistic and compassionate approach to patient care. The Loebs’ imprint on the health-care field through support of medical education is far reaching and long lasting.”

The Loeb fellowship is also supported by The Foundation for Barnes-Jewish Hospital.

With his fellowship, Ahmad will develop a longitudinal financial well-being curriculum for pediatric trainees. Early in his career, Ahmad recognized the need for financial education among medical trainees. Over the past 10 years, he has led a popular financial education lecture series equipping pediatric and internal medicine residents with skills for long-term financial security, including loan repayment strategies and retirement planning. The fellowship also will help him integrate the curriculum into the residents’ studies and incorporate several educational methods, including workshops and simulations.

“We’re often taught when we pursue careers in medicine that finances and money shouldn’t matter and often hear that physicians shouldn’t manage their finances,” Ahmad said. “It has led to a culture of discomfort discussing financial topics with our peers and trepidation over learning about it. We are harming current and future generations of physicians with this approach, and I hope with this expanded, integrated curriculum, we can do better for our trainees.”

Fraum’s fellowship project aims to revamp the radiologic physics curriculum for resident trainees at Mallinckrodt Institute of Radiology. Understanding radiologic physics is critical for residents because it is the basis for optimizing images, recognizing artifacts, building protocols and minimizing radiation risk.

“Historically, radiologic physics has been a bitter pill for many residents — a necessary but often unpleasant aspect of their training,” Fraum said. “The curriculum I plan to build, in collaboration with several other radiologists and physicists in our department, will incorporate active learning strategies, such as audience participation and case-based formats to enhance resident engagement. Furthermore, it will focus on practical, clinically relevant topics that residents are likely to encounter throughout their careers. Overall, our goal is to make the radiologic physics curriculum cognitively nourishing yet enjoyable — in other words, to transform it from a bitter pill into a gummy vitamin.”