Siteman Cancer Center’s parent institutions have named two new leaders in radiation oncology.

Kinzel

Dan Kinzel is executive director of radiation oncology at Washington University School of Medicine. Sharon Endicott is director of radiation oncology for Barnes-Jewish Hospital.

They oversee radiation oncology operations at:

• The S. Lee Kling Center for Proton Therapy at Washington University Medical Center;
  
• Siteman Cancer Center-South County in south St. Louis County;
  
• Siteman Cancer Center at Barnes-Jewish West County Hospital in Creve Coeur;
  
• ​Siteman Cancer Center at Barnes-Jewish St. Peters Hospital in St. Charles County.
  

Endicott

Endicott had been Barnes-Jewish Hospital's interim director of radiation oncology since August. As director, she will continue to work with faculty and staff members to promote patient safety, quality assurance and performance improvement throughout the radiation oncology department.

Before she was interim director, Endicott served as technical service manager of radiation oncology at Siteman for five years.

“We have a long history of being a national and international leader in radiation oncology,” Endicott said, “and I look forward to working with my colleagues at Siteman Cancer Center, Washington University and BJC in continuing to provide world-class cancer care to our patients.”

Endicott received a bachelor’s degree in health-care leadership from the University of St. Francis in Joliet, Ill. She is a certified medical dosimetrist and a radiation therapist.​​​​

“I’m excited to be joining the nationally and internationally recognized Department of Radiation Oncology as executive director,” he said. “I’m looking forward to working in collaboration with the team at Washington University, Siteman Cancer Center and BJC to continue the advancement of services and care in our region.”

Kinzel received a master’s degree in business administration from Saint Louis University and a bachelor’s degree in science, marketing and finance from the University of Dayton, Ohio.

Robert Boston

William Gillanders, MD, is developing a vaccine aimed at harnessing the immune system to fight breast cancer. If proven effective as a cancer treatment, the vaccine someday could be used to prevent breast cancer, too.

“There is a metaphor there,” he said. “My goal is to change breast cancer treatment paradigms, to make vaccines a reality for women who are being treated for breast cancer. That’s an ambitious goal but one that I think I can tackle. It’s a career goal; it’s not one that can happen overnight. It’s like preparing for a 100-mile century ride. It is a goal that you have to really work on to make it a reality. Of course, a breast cancer vaccine is much more challenging.”

Your research centers on something many never considered possible – a vaccine for breast cancer. Tell us about your work.

The goal of a cancer vaccine is to harness the immune system to fight cancer. Recent studies confirm that the immune system plays an important role in controlling the growth of cancer. Our vaccine targets a protein, mammaglobin-A, that is expressed in almost all breast cancers. The vaccine trains the immune system to find and destroy cells with this protein. If the vaccine proves effective as a cancer treatment, it may someday be used to prevent breast cancer, too.

How long have you been working on this?

I’ve been interested in mammaglobin biology for more than 10 years. My interest predates my recruitment to Washington University in 2005. At the Medical University of South Carolina, where I was previously on the faculty, we were using mammaglobin as a molecular marker for detecting metastatic breast cancer either in the lymph nodes, bone marrow or peripheral blood. It is one of the best molecular markers for the detection of breast cancer.

A main reason why I chose to come back to Washington University – I was a trainee here in general surgery from 1991-99 – was the opportunity to be part of a multidisciplinary team working to develop breast cancer vaccines. We have a very strong immunology community at Washington University School of Medicine, and I’ve been thrilled with the generosity and willingness of investigators here to collaborate.

Talk about the potential of cancer immunotherapy.

It’s very similar to the story of antibodies for cancer therapy. When antibodies were first identified, the thought was that they’d be the magic bullet. The initial studies with antibody therapy were underwhelming; they were only marginally successful, if that. But we learned a lot in those studies about how and when to use antibody therapies. Now, they’re really a mainstay of modern cancer treatment.

The same is true of immunotherapy. Initially, there was great enthusiasm because of the potential promise, but it’s only because the initial studies were not successful that we were able to learn how to best use immunotherapy. Part of the reason why the enthusiasm has returned is because of the dramatic success of recent immunotherapy trials.

Give us a broad overview of breast cancer vaccine research.

The vaccine landscape has changed quite a bit. Five years ago, there might have been three to five breast cancer vaccine trials nationwide. Now there probably are 20-plus. There’s a growing realization that, if used appropriately, vaccine therapy can be effective.

Is the holy grail a vaccine that could prevent cancer in the first place? Is that the ultimate goal of your research?

That’s right. The holy grail would be a vaccine that could prevent the development of cancer. But several steps must be accomplished before we get there. The first is development of a vaccine that’s safe and very effective. Once we have that, we’ll start to use it in early-stage disease or in women who are at high risk for breast cancer and then, ultimately, in healthy women.

I know there’s a lot of frustration that you can’t just move forward to evaluate these vaccines in healthy women, but the reality is, if you’re going to give an investigational treatment to healthy individuals, you have to have enormous confidence that it is safe and effective. There has to be an appropriate balance between the potential risks of an investigational agent and the benefits.

Switching gears, you’re an active cyclist and a daily bike commuter. How many miles a week do you ride?

I don’t track how many miles or hours I ride, but I ride my bike to work every day. It’s a great way to start and end the day. In the morning, it wakes you up and gets you ready for everything you need to do. And in the evening, it wipes the slate clean so you don’t bring any stress home. I’m very lucky because I have a very pleasant commute. I bike through Forest Park, up and down Wydown Boulevard and through Shaw Park.

Bike commuters tend to take in more of what’s going on around them. What are some things you’ve seen while riding to and from campus?

I’ve seen all kinds of wild animals. There’s a family of foxes that lives around Wydown Boulevard in Clayton. In Forest Park, there’s a mated pair of owls that has baby owls every year. It’s fun to track their progress. We’re just getting into the season now when you’ll be seeing lots of baby geese. There are all kinds of raccoons and other wild animals in the park.

Courtesy of W. Gillanders

Jeanne (top left) and William Gillanders have three children. They are (from left) Teddy, Emma and Ian. "They are very supportive of me and my work, so I’m very, very appreciative of their understanding and patience," William Gillanders said.

That sounds like a relaxing transition to home. Tell us a little about your life there.

I’m very fortunate to have a fantastic family. My wife, Jeanne, is a teacher, so she sets the tone for the kids and the importance of schoolwork. And we have three kids who are growing up very quickly. My daughter, Emma, is a freshman in high school. Our son Ian is in seventh grade, and our other son, Teddy, is in fifth grade. They’re a lot of fun. They are very supportive of me and my work, so I’m very, very appreciative of their understanding and patience. Whenever I travel I miss home quite a bit.

Talk about being a physician-scientist. The two are related, of course, but also very different.

I have one foot in the clinical realm and one foot in the research realm. My goal is to bridge those two worlds, to collaborate with all the great basic scientists here at Washington University School of Medicine and help them move their great ideas into the clinic.

Your father is a physician, too. What medicine did he practice? Was he the inspiration behind what you’re doing today?

Yes, my father is a retired obstetrician-gynecologist, in one of the surgical subspecialties. I remember him talking about surgery when I was younger.

One of the things I’ve enjoyed quite a bit with my father recently is that when he comes to visit he likes to walk. So I set aside my bike and we walk to work together. He’s in his 70s, and he walks fast. That’s really been a great time to bond with him. My father and I have seen some of the wildlife I mentioned earlier. One morning we were visited by a bald eagle that flew right over our heads. It’s an hour-and-45-minute walk, and often as we trek through Forest Park the sun comes up. It’s a great way for my father and me to spend time together.

Another way you’ve combined your work and personal life is through Pedal the Cause, the annual cycling fundraiser for cancer research at Siteman Cancer Center and St. Louis Children’s Hospital. You’ve received grants from the group; you’re a participant in the bike ride.

I’ve been an avid cyclist for many years, and I remember meeting the founder, Bill Koman, before the first Pedal the Cause in 2010. He was very excited about the event, and I share his passion and enthusiasm.

I’ve done every Pedal the Cause so far. Initially, I was captain of the Siteman Cancer Center team. Since then, individuals from that original team have gone on to start eight or 10 new teams. These teams are focused on difference cancers, such as breast cancer, pancreas cancer, lymphoma, head and neck cancer, prostate cancer and other cancers. There’s a lot of enthusiasm for Pedal the Cause, and I’ve had a lot of fun doing it. I just wish that the funding decisions would integrate finishing time into the overall algorithm for deciding on who is funded!

What kind of patients would be helped by your research?

We have two clinical trials in the works. One is already open to patients; the other soon will be. For the open trial, we’re recruiting newly diagnosed patients to study the safety and effectiveness of our mammaglobin-A vaccine. For the other trial​, we will recruit 30 patients. Although it remains to be determined what cancer patients will benefit most from these vaccines, I think there is potential that vaccines ultimately will be used in all stages of the disease.​

Washington University diabetes researcher Carlos Bernal-Mizrachi, MD, shown with a mouse that lacks the ability to process vitamin D in key immune cells. Without adequate vitamin D in those cells, the animals developed diabetes and atherosclerosis.

In recent years, a deficiency of vitamin D has been linked to type 2 diabetes and heart disease, two illnesses that commonly occur together and are the most common cause of illness and death in Western countries. Both disorders are rooted in chronic inflammation, which leads to insulin resistance and the buildup of artery-clogging plaque.

Now, new research in mice at Washington University School of Medicine in St. Louis suggests vitamin D plays a major role in preventing the inflammation that leads to type 2 diabetes and atherosclerosis. Further, the way key immune cells behave without adequate vitamin D may provide scientists with new therapeutic targets for patients with those disorders.

The study appears March 19 in the journal Cell Reports.

Studying mice that lacked the ability to process vitamin D in immune cells involved in inflammation, the researchers found that the animals made excess glucose, became resistant to insulin action and accumulated plaques in their blood vessels.

“The finding that vitamin D helps regulate glucose metabolism may explain previous epidemiological studies identifying an increased risk of diabetes in patients with vitamin D deficiency,” said senior investigator Carlos Bernal-Mizrachi, MD, associate professor of medicine and of cell biology and physiology. “In our study, inactivation of the vitamin D receptor induced diabetes and atherosclerosis, so normalizing vitamin D levels may have the opposite effect.”

In addition, he said inadequate vitamin D turned immune cells into transporters of fat. That may help researchers better understand how diabetes and atherosclerosis are linked and provide new possibilities for therapy.

For years, researchers have been studying vitamin D’s possible roles in inflammation and inflammatory diseases, such as type 2 diabetes and atherosclerosis. By engineering mice without the vitamin D receptor on important immune cells called monocytes and macrophages, the researchers were able to learn how those conditions are linked, according to Bernal-Mizrachi.

Monocytes are white blood cells made in the bone marrow that circulate in the bloodstream. After a few days, they typically move into the body’s tissues where they mature into cells called macrophages.

“Inactivating the vitamin D receptor on monocytes and macrophages promotes inflammation of the liver and in artery walls,” he said. “It also increases the ability of monocytes in the blood to adhere and migrate into blood vessel walls, where they deposit cholesterol and secrete inflammatory substances that lead to diabetes and heart disease.”

He said the findings suggest that getting enough vitamin D may reduce those properties in immune cells, decreasing inflammation and reducing the onset of a combination of heart disease and diabetes, which is often referred to as cardiometabolic disease. In addition, the researchers found that without vitamin D, monocytes carried fat to the walls of blood vessels, which is something that hadn’t been observed previously.

“We knew that when monocytes matured and became macrophages, they would eat cholesterol deposited inside the blood vessel wall,” said co-first author Amy E. Riek, MD, assistant professor of medicine. “But in these experiments, we found that when they don’t have vitamin D, the monocytes, while they’re still in circulation, also eat up cholesterol and carry it in the bloodstream.”

That’s an important discovery, Riek explained, because it’s much easier to find treatments that target something in the blood than it is to target the same cells after they move into the wall of a blood vessel.

“So that provides us, potentially, with a new target for therapy,” she said.

Riek

It also changes the way that scientists think about how lipids are carried into the blood vessel wall to cause plaques. Scientists already knew that LDL, the so-called bad cholesterol, carried fat deposits to the vessel wall. Now this study suggests that when monocytes don’t have enough vitamin D, they can do it, too.

“The monocytes were laden with fat in the absence of vitamin D receptor,” Bernal-Mizrachi said. “And they carried that fat into the artery, so that’s a new understanding of another way fat may get into blood-vessel walls in patients who are vitamin D deficient.”

Interestingly, the problem was reversible in the mice. When the animals that had developed type 2 diabetes and atherosclerosis received bone marrow transplants from mice with healthy vitamin D receptors on their monocytes and macrophages, their inflammation levels decreased, and the animals had lower blood glucose and became more sensitive to insulin.

Currently, Bernal-Mizrachi and Riek are conducting clinical studies in people who have type 2 diabetes, treating them with vitamin D to see whether it can prevent some of the complications of diabetes and inflammation in humans, too.

“As part of that study, we’re actually isolating monocytes from the blood of patients before and after vitamin D therapy,” Riek said. “So we can look at the inflammatory properties of those cells to see whether vitamin D is causing any changes.”

Funded by grants from the National Heart, Lung and Blood Institute (NHLBI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), the Children’s Discovery Institute, and the American Diabetes Association. NIH grant numbers R01HL094818-0, K12HD001459, UL1 TR000448, KL2 TR000450. T32 DK007120 and P60DK20579.

Oh J, Riek AE, Darwech I, Funai K, Shao JS, Chin K, Sierra OL, Carmelier G, Ostlund RE, Bernal-Mizrachi C. Deletion of macrophage vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice. Cell Reports, published online March 19, 2015. 

Robert Boston

During Match Day festivities at the School of Medicine, Justin Krogue carries his son, Miles, while his wife, Marissa, reveals where Justin will receive his residency training. They learned they will relocate to the University of California, San Francisco, where Justin will train in orthopedic surgery. Visit this School of Medicine page for more photos from Match Day. 

The first day of spring, March 20, also happened to be the day medical students across the country found out where they will head for their residency programs, the next stage in their medical careers.

At Washington University School of Medicine, more than 120 students gathered at the Eric. P. Newman Education Center for the much-awaited delivery of envelopes that contained news of where the soon-to-be graduates had matched.

Robert Boston

Allan Jiang celebrates at Match Day, where he learned he will train in psychiatry at Barnes-Jewish Hospital.

Kathryn Diemer, MD, assistant dean for career counseling, called each student to the stage to receive such an envelope. Each student had chosen a song that played as they made their way to the stage. Selections — some serious, some silly — included “Let it Go” from Disney’s “Frozen,” to the “Jeopardy!” theme song, to Green Day’s “Time of Your Life.”

As they approached the microphone to announce their specialties and where they had matched, each student placed $1 in a bin. Tradition has it that the cash goes to the student whose name is called last. The students are called randomly, so the loot goes to the person who had to wait the longest for such big news.

To make it easier for families, however, students with small children were called first.

Katie Ihnen’s family came to the front with her, including her husband, Alex, and children Lucy, Oscar and Harriet. Ihnen happily relayed that she had matched in pediatrics at St. Louis Children’s Hospital.

Robert Boston

Pankaj Pal (right) and her boyfriend, Adam Zuiani, learn she will train in internal medicine at Beth Israel Deaconess Medical Center in Boston.

There was no doubt where student Allan Jiang hailed from as he made his way down the steps, dressed in full Canadian hockey paraphernalia. He had trouble opening his envelope because of the hockey stick he carried and mittens he wore. But after a struggle, he tore into the envelope to learn that he would be staying in St. Louis to train in psychiatry at Barnes-Jewish Hospital.

Overall, 123 medical students matched in 22 specialties in a total of 23 states. Top specialties included internal medicine, pediatrics, obstetrics-gynecology, orthopedic surgery and anesthesiology.

To see more photos from Match Day, visit this School of Medicine page.

Yun Ju Sung, PhD, assistant professor of biostatistics and of psychiatry at Washington University School of Medicine in St. Louis, has received a five-year, $718,950 grant from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) for research titled “Statistical Methods For Genomic Dissection of Cardiovascular Diseases.”

CDC/James Archer

Bacteria that cause many hospital-associated infections are ready to quickly share genes that allow them to resist powerful antibiotics. The illustration, based on electron micrographs and created by the Centers for Disease Control and Prevention, shows one of these antibiotic-resistant bacteria.

Antibiotic resistance is poised to spread globally among bacteria frequently implicated in respiratory and urinary infections in hospital settings, according to new research at Washington University School of Medicine in St. Louis.

The study shows that two genes that confer resistance against a particularly strong class of antibiotics can be shared easily among a family of bacteria responsible for a significant portion of hospital-associated infections. 

Drug-resistant germs in the same family of bacteria recently infected several patients at two Los Angeles hospitals. The infections have been linked to medical scopes believed to have been contaminated with bacteria that can resist carbapenems, potent antibiotics that are supposed to be used only in gravely ill patients or those infected by resistant bacteria.

“Carbapenems are one of our last resorts for treating bacterial infections, what we use when nothing else works," said senior author Gautam Dantas, PhD, associate professor of pathology and immunology. "Given what we know now, I don't think it's overstating the case to say that for certain types of infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we rely on to treat bacterial infections are no longer effective.”

Dantas and other experts recommend strictly limiting the usage of carbapenems to cases in which no other treatments can help.

The study, conducted by researchers at Washington University, Barnes-Jewish Hospital and the National University of Sciences and Technology in Pakistan, is available online in Emerging Infectious Diseases.

The researchers studied a family of bacteria called Enterobacteriaceae, which includes E. coli, Klebsiellapneumoniae and Enterobacter. Some strains of these bacteria do not cause illness and can help keep the body healthy. But in people with weakened immune systems, infections with carbapenem-resistant versions of these bacteria can be deadly.

The Centers for Disease Control and Prevention named carbapenem-resistant Enterobacteriaceae as one of the three most urgent threats among emerging forms of antibiotic-resistant disease. Studies have shown the fatality rate for these infections is above 50 percent in patients with weakened immune systems.

Two genes are primarily responsible for carbapenem-resistant versions of these disease-causing bacteria. One gene, KPC, was detected in New York in 2001 and quickly spread around most of the world, with the exception of India, Pakistan and other South Asian countries. This gene was present in the bacteria that recently contaminated medical equipment in a Los Angeles hospital where two patients died.

A second carbapenem resistance gene, NDM-1, was identified in 2006 in New Delhi, India. It was soon detected throughout South Asia, and most patients infected by bacteria with NDM-1 have had an epidemiological link to South Asian countries.

Dantas and his collaborators were curious about why the two resistance genes seemed to be geographically exclusive. For the study, they compared the genomes of carbapenem-resistant bacteria isolated in the United States with those of carbapenem-resistant bacteria isolated in Pakistan.

Based on the apparent geographic exclusivity of the two resistance genes, the scientists expected to find that bacteria from the two regions were genetically different. Such differences could explain why the two resistance genes weren’t intermingling. But the researchers' results showed otherwise. The bacteria’s high genetic similarity suggests that the antibiotic resistance genes could be shared easily between bacteria from the two geographic regions.

The researchers also sequenced a special portion of bacterial genetic material called plasmids. Most of a bacteria’s DNA is found in its chromosome, but bacteria also have many extra, smaller and circular bits of DNA known as plasmids that easily can pass from one bacterial strain to another. A plasmid is like a bacterial gene delivery truck; it is the primary way antibiotic resistance genes spread between bacteria.

The researchers identified a few key instances in which the plasmids carrying NDM-1 or KPC were nearly identical, meaning they easily could facilitate the spread of antibiotic resistance between disease-causing bacteria found in the United States and South Asia. Recent evidence suggests that this intermingling already may be happening in parts of China.

“Our findings also suggest it’s going to get easier for strains of these bacteria that are not yet resistant to pick up a gene that lets them survive carbapenem treatment,” Dantas said. “Typically, that’s not going to be a problem for most of us, but as drug-resistant forms of Enterobacteriaceae become more widespread, the odds will increase that we’ll pass one of these superbugs on to a friend with a weakened immune system who can really be hurt by them.”

Six researchers at Washington University in St. Louis are being honored as outstanding scientists by the Academy of Science-St. Louis.

University recipients of this year’s honors are faculty members Steven Teitelbaum, Ralph Quatrano, Jennifer K. Lodge, Samuel Achilefu, Charles M. Hohenberg and Gautam Dantas.

Also honored with a Science Leadership Award is the CORTEX Innovation Community, of which Washington University is a valuable member. Other CORTEX members include BJC HealthCare, University of Missouri-St. Louis, Saint Louis University and the Missouri Botanical Garden.

Each year, the academy seeks nominations of outstanding women and men in science, engineering and technology who are known worldwide for their scientific contributions to research, industry and quality of life. Those recognized also have a record of excellence in communicating with the public and/or mentoring colleagues.

The awards, which will be given at a dinner Thursday, April 9, represent recognition by St. Louis’ scientific community, the Academy’s Board of Trustees and members of the Academy of Science-St. Louis.

Teitelbaum

Steven L. Teitelbaum, MD

The Wilma and Roswell Messing Professor of Pathology and Immunology and a professor of medicine at Washington University School of Medicine in St. Louis, Teitelbaum has produced an extensive collection of important discoveries about the cells and regulatory factors that control the renewal of the skeleton, which is regularly demolished and rebuilt to keep it strong.

He also has been a leader in development and adaptation of new techniques for diagnosis and treatment of bone disease. When French physicians developed the first technique for extracting bone samples to diagnose disease, he traveled to France to learn the technique and brought it back to St. Louis.

A strong advocate for scientific freedom, Teitelbaum speaks out often about the potential benefits of stem cells and cloning, and opposes legal prohibitions on the use of these and other scientific tools and techniques.

Quatrano

Ralph Quatrano, PhD

Quatrano will receive the Science Leadership Award, which recognizes distinguished individuals who have played important leadership roles in the development of science and scientists in the St. Louis area.

Quatrano, who will step down as dean of the School of Engineering & Applied Science on June 30, has had a distinguished career that includes leadership positions at several top universities, in industry and in entrepreneurship. He is internationally renowned for his work on the hormonal regulation of gene regulatory networks in model organisms and in crop plants to understand how to better engineer plants to grow in water-scarce environments.

His previous leadership roles at Washington University include that of chair of the Department of Biology in Arts & Sciences, during which time he directed a 10-year research program in plant science between Monsanto and the university. He also was director of the Division of Biology and Biomedical Sciences, as well as dean of the Faculty of Arts & Sciences. He also co-founded MOgene LLC, a St. Louis-based genomic services company.

Lodge

Jennifer K. Lodge, PhD

Lodge, the university’s vice chancellor for research and the associate dean for research at the School of Medicine, will receive a Trustees Award. The honor recognizes outstanding contributions to the Academy of Science-St. Louis in its mission of promoting the understanding and appreciation of science, engineering and technology.

A Washington University graduate, Lodge was named a fellow of the American Association for the Advancement of Science in 2011 and a fellow of the American Academy of Microbiology in 2010. She continues to pursue NIH-funded research on mechanisms of fungal pathogenesis, anti-fungal drug discovery and vaccine development.

Achilefu

Samuel Achilefu, PhD

Achilefu, who also is a professor of radiology, of biomedical engineering and of biochemistry and molecular biophysics, leads a team that has identified a novel molecular agent that specifically targets and remains longer in cancer cells than other current options, providing a unique opportunity to zero in on most tumors, using a single imaging agent.

His team has developed high-tech goggles that help surgeons visualize cancer cells. The cells, which are notoriously difficult to see, glow blue when viewed through the eyewear, helping to ensure that no stray tumor cells are left behind during surgery. His group also is developing a light-based cancer therapy aimed at overcoming the difficulty in reaching tumors in deep tissue with light.

Hohenberg

Charles M. Hohenberg, PhD

Hohenberg, professor of physics in Arts & Sciences, will receive a James B. Eads Award, which recognizes a distinguished individual for outstanding achievement in engineering or technology.

In 1975, Hohenberg designed and built a unique noble gas mass spectrometer, one capable of single atom detection and of analyzing the isotopic structures of samples containing only a few thousand noble gas atoms. Focused laser heating allows the noble gases contained in individual mineral grains to be routinely studied.

Applied to a variety of problems, this instrument has opened up new research in many areas. It has allowed Hohenberg and his colleagues to better delineate early solar system chronology using a precise I-Xe dating method he pioneered. He used it to decipher irradiation records of individual meteoritic grains revealing the active early (T-Tauri) Sun, to determine the ages of lunar craters, to put an upper limit on the mass of the electron neutrino, and to analyze tiny particles from a comet nucleus and the noble gases from the solar wind.

He also has been a key science team member on NASA missions, including the Stardust and Genesis missions.

Dantas

Gautam Dantas, PhD

Dantas, associate professor of pathology and immunology and of biomedical engineering, will receive the Innovation Award, which recognizes a scientist or engineer 40 or younger, who has demonstrated exceptional potential for future accomplishments in science, engineering or technology.

Dantas has used the latest techniques for genetic sequencing and analysis to study the origins and evolution of bacterial resistance to antibiotics. Bacteria can share genes much more easily than higher organisms, and Dantas has pioneered methods that let scientists trace the origin and historic spread of genes that help bacteria survive exposure to antibiotics.

He also is working to use these techniques to predict the future spread of these antibiotic resistance genes and is using that information to advocate against the overuse of these drugs in clinical care and in agriculture.

A new test from Washington University's Genomic Pathology Services will help physicians quickly zero in on genetic mutations that may be contributing to kidney disease.

Many kidney disorders are difficult to diagnose. To address this problem, scientists and clinicians have developed a diagnostic test that identifies genetic changes linked to inherited kidney disorders. This testing is now available nationwide through Genomic Pathology Services (GPS) at Washington University School of Medicine in St. Louis.

To make this possible, the GPS team developed the test with kidney disease specialists, including Joseph Gaut, MD, PhD, a renal pathologist. 

The test employs next-generation sequencing technology to decode genes associated with kidney disease. Using software developed at the university, clinical genomics specialists analyze and interpret the observed genetic alterations to identify disease-related genetic changes, or variants. They then must determine whether a given variant poses clinical risks based on available medical knowledge.

“The variants have to be evaluated on a case-by-case basis, which can be time-consuming and labor-intensive,” Heusel said.

GPS continues to update the kidney test as new links between kidney problems and DNA are identified.

“We stay abreast of the literature, and as new genes become clinically meaningful, we will incorporate those into the test,” said Catherine Cottrell, PhD, medical director for GPS.

The kidney test will check for:

• Alport syndrome, which is characterized by progressive loss of kidney function, hearing loss and eye abnormalities;

• Nephrotic syndrome, which includes symptoms such as protein in the urine, low blood-protein levels, high levels of cholesterol and triglycerides, and swelling;

• Metabolic disorders associated with renal disease and including other systemic abnormalities such as diabetes, amyloidosis and others;

• Complement (immune system) defects related to kidney disease, including atypical hemolytic uremic syndrome.

Physicians interested in kidney genetic testing for their patients may contact GPS, which assists with insurance preauthorization for the service.

For the analysis, physicians submit a blood sample from the patient. GPS analyzes the sample and sends the physician a report outlining the results in four to six weeks.

GPS recommends that physicians make genetic counseling available to patients to help them understand and manage their diagnoses and any health implications for family members.

For more information, contact GPS by phone at 314-747-7337 (toll-free 866-450-7697), email at gps@wustl.edu or visit the website.

Zeynep Yurtsever, a biochemistry graduate student, and Daniel Kober, a microbiology graduate student, both in the laboratory of Thomas Brett, PhD, assistant professor of medicine at Washington University School of Medicine in St. Louis, have received two-year, $52,000 fellowships from the American Heart Association. 

Yurtsever's research is titled “Mechanism of CLCA-mediated Regulation of Ca-activated Cl Channels"; Kober's is titled “Structural and Functional Consequences of TREM-2 Mutants Linked to Neuroinflammation.”

Rao

Davila-Roman

D.C. Rao, PhD, director of the Division of Biostatistics, professor of biostatistics and of biostatistics in genetics and psychiatry at Washington University School of Medicine in St. Louis, and Victor G. Davila-Roman, MD, professor of medicine, of anesthesiology and of radiology, have received a four-year, $1.28 million grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) for a program titled “PRIDE Summer Institute in Cardiovascular Genetic Epidemiology.”

David C. Beebe, PhD, the Janet and Bernard Becker Professor of Ophthalmology and Visual Sciences, died at his home in St. Louis on Friday, March 27, 2015, from complications of amyotrophic lateral sclerosis (ALS). He was 70.

Beebe

A longtime leader in the Department of Ophthalmology and Visual Sciences at Washington University School of Medicine in St. Louis, Beebe headed the Cataract Research Center. His research focused on the early development of the eye and the causes and potential prevention of nuclear cataracts and glaucoma.

Also a professor of cell biology and physiology, he was the recipient of a School of Medicine Distinguished Educator award in 2014. Also last year, he was honored with the creation of an endowed lectureship in his name.

“The Dr. David C. Beebe Lecture celebrates the scientific curiosity, translational research, mentorship and passion that Dr. Beebe brought to our field, as well as the 20 years of service he brought to the department," said Todd Margolis, MD, PhD, the Alan A. and Edith L. Wolff Distinguished Professor and Chairman of Ophthalmology and Visual Sciences. “He made outstanding contributions to research and to the education of young scientists. The department will miss his expertise and the wisdom and insight he provided to his trainees.”

Beebe joined the Washington University faculty in 1995. During his tenure, he was very involved in the Association for Research in Vision and Ophthalmology (ARVO), serving in various capacities over the past 20 years. He served on its board of trustees from 1996-2002, and in 2000 was elected the organization's president. He also served as editor in chief of the ARVO journal Investigative Ophthalmology and Visual Sciences.

Beebe recently was chosen to receive ARVO’s highest service award, the annual Joanne G. Angle Award. His wife will accept the honor on his behalf at the organization's annual meeting in May.

Beebe earned a bachelor’s degree in zoology from the University of Rhode Island and a master’s degree in biomedical sciences at Brown University. He then earned a doctorate in biology at the University of Virginia, where he received the Andrew Fleming award as the outstanding graduate student in biology.

After a postdoctoral fellowship at the National Institutes of Health (NIH), he took a faculty position in the Department of Anatomy at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. He eventually became chairman of the Department of Anatomy and Cell Biology and was chosen by the medical students to receive two Golden Apple Awards for outstanding teaching during his tenure there.

Beebe is survived by his wife of 37 years, Anne-Elizabeth; three children, Peter (Fay Bouman), Colin (Jennifer Sullivan) and Jessica (Philip Quitslund); and four grandchildren.

A memorial service will be held May 16 at the School of Medicine. More details will be available soon.

Memorial contributions may be made to the Dr. David C. Beebe Lectureship Endowment Fund; Department of Ophthalmology and Visual Sciences at Washington University School of Medicine; Attn: Kevin Largent; 7425 Forsyth Blvd., Campus Box 1247; St. Louis, Missouri 63105; or to ARVO.

Rice

Treva K. Rice, PhD, professor of biostatistics and of psychiatry at Washington University School of Medicine in St. Louis, has received a four-year, $1.79 million grant from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) for research titled “PRIDE Coordination Center.” 

The grant is to fund collection of data from summer training programs for junior faculty who are underrepresented in the biomedical sciences and to investigate factors leading to their successful career development.

Pediatric cardiologist Patrick Jay, MD, PhD, and his team showed that with exercise, older mouse mothers genetically predisposed to bear mice with congenital heart defects reduce the risk of such defects to that of younger mouse mothers with the same genetic predisposition.

In people, a baby’s risk of congenital heart defects is associated with the age of the mother. Risk goes up with increasing age. Newborn mice predisposed to heart defects because of genetic mutations show the same age association.

A new study demonstrates that older mouse mothers reduce this risk for their offspring to that of younger mouse mothers through exercise alone, according to researchers at Washington University School of Medicine in St. Louis. The study also suggests that the increased risk of congenital heart defects is tied to the age of the mother and not the age of her eggs.

The study appears April 1 in Nature.

The risk that an infant human or mouse may develop a congenital heart defect results from a complex interplay of genes inherited from both parents and environmental effects experienced by the embryo. Genetic mutations are known to increase a child’s risk of developing a heart that has abnormally formed valves, vessels or chambers, or holes between the chambers. However, many people who have family histories of congenital heart disease or known mutations have normal hearts, and older mothers usually have healthy children.

“Conventional wisdom says this increased risk seen for older mothers results from aging eggs,” Jay said. “Since all of a woman’s eggs were produced when she was an embryo, there’s this notion that over decades the eggs just go bad. But the evidence for this is pretty circumstantial. In humans, you can only show associations. You can’t establish causality.”

To look at the question of aging eggs more carefully, Jay and his colleagues performed a relatively simple experiment, yet one that, to his knowledge, has not been reported previously.

Working in mice genetically prone to relatively high rates of congenital heart defects, the researchers took ovaries from older mothers and transplanted them into younger mothers. Likewise, they took the ovaries of younger mothers and transplanted them into older mothers. They examined the offspring to determine if higher rates of heart defects tracked with the age of the mothers or the age of the ovaries.

“We discovered that the rates track exactly with the age of the mother,” said Jay, also a pediatric cardiologist at St. Louis Children’s Hospital.

In other words, young mice with old ovaries bore offspring with low rates of heart defects, similar to young mice with young ovaries. And older mice, even with young ovaries, bore offspring with higher rates of heart defects, similar to older mice with older ovaries.

“This is exciting from a prevention standpoint,” Jay said. “If there is something about the mother that is contributing to the risk, independent of the ovary, then we have a much better chance of altering that risk than we would if the problem were solely with aging eggs — simply because adults are easier to treat than eggs or embryos.”

In an effort to identify possible drivers of age-associated risk of congenital heart disease, Jay and his team looked at diet.

“We knew that obesity and diabetes contribute to congenital heart disease in people and that the risk of these metabolic conditions goes up as you age,” he said. “So we put the mice on a high-fat diet.”

Despite becoming obese and diabetic, these mouse mothers did not have a greater risk of bearing offspring with increased heart defects. Still thinking that healthy metabolism was likely important for healthy developing embryos, Jay and his colleagues next looked at exercise.

“We gave the mice access to running wheels, like you would find at a pet store,” he said. “And we just let the mothers run.”

This time, the researchers found that risk of heart defects in offspring of older mothers dropped from about 20 percent for sedentary mothers to 10 percent for exercising mothers. They didn’t see a significant effect of exercise in the younger mothers, with rates staying at about 10 percent for them regardless of physical activity.

“In the babies of the old mothers who exercised, the incidence of heart defects goes down, but it does not go below the incidence of the young mothers,” Jay said. “There’s still a baseline level that we didn’t get past.”

Even so, Jay said, cutting rates in half would be significant.

“If you can prevent even one heart defect, that can have a huge emotional and economic impact on a family,” Jay said. “While we’ve gotten very good at treating congenital heart defects, the surgeries don’t cure the patients. Now that so many have reached adulthood, we know they are coming back with heart failure, arrhythmias and other difficult heart problems.”

While Jay said they don’t know how such data might translate into people, they showed that exercise did not have to be life-long to produce a measurable benefit. Older mouse mothers who exercised for at least three months prior to birth saw an effect similar to that seen in older mothers who had exercised since they were the equivalent of teenagers. Jay explained that the benefit was observed with high-intensity physical activity by human standards. Mice like to run and, if given the opportunity, will do so for most of their waking hours.

Still, Jay said, they are pleased to have demonstrated the concept that a treatment or intervention focused on the mother can prevent disease in the offspring that carries the causal mutation.

“I hope this study will change the way investigators think about congenital heart disease,” he said. “Right now, the field is very focused on the embryo — finding genetic mutations and figuring out the biology to see how they affect cardiac development. That research is important and necessary, but this opens up a whole new conversation.”

Sullivan

Louis W. Sullivan, MD, president emeritus of Morehouse School of Medicine and former secretary of the U.S. Department of Health & Human Services (HHS), will speak about health equity and diversity in the health professions in two talks April 9 at Washington University.

His talk, “Efforts to Achieve Health Equity in the Nation,” will be at 8 a.m. in Clopton Auditorium at Wohl Clinic on the Medical Campus as part of grand rounds for the Department of Medicine. At noon in Brown Lounge in Brown Hall on the Danforth Campus, he will give a talk titled “Strategies to Increase Racial and Ethnic Diversity in the Health Professions” as part of the Brown School’s Distinguished Lecture Series.

Sullivan is chairman of the board of the Nation Health Museum in Atlanta. The museum’s goal is to improve the health of Americans by enhancing health literacy and advancing healthy behaviors. He also is chairman of the Sullivan Alliance to Transform the Health Professions.

Sullivan was founding dean of Morehouse School of Medicine, the first predominantly black medical school established in the country. And from 1989-93, he served as secretary of HHS in the administration of President George H.W. Bush.

His visit is sponsored by the Department of Medicine, the Brown School and the Institute for Public Health.

M. Gilbert Grand, MD, has been elected president of The Macula Society.

A clinical professor of ophthalmology at Washington University School of Medicine for 35 years, Grand specializes in diseases of the retina, macula and vitreous with The Retina Institute of St. Louis. He was named the new president of the society at the group’s annual meeting in Scottsdale, Ariz.

Grand

A graduate of Tufts University and Yale University School of Medicine, Grand came to Washington University in 1972 as a resident in ophthalmology and later completed a retina fellowship here.

In addition to the Macula Society, Grand is active in the American Academy of Ophthalmology, the Retina Society, the St. Louis Ophthalmological Society, the American Ophthalmological Society and the American Society of Retina Specialists.

Founded in 1977, The Macula Society is a forum for new research in retinal vascular and macular diseases. Its 444 members are internationally recognized specialists in the diagnosis and management of vitreo-retinal diseases. At the 2015 meeting, Grand presented his most recent research, on vitreo-retinal surgery in patients taking anticoagulant drugs that reduce the ability of the blood to clot.

At the School of Medicine, Grand is a past recipient of the Dr. Neville Grant Award for Clinical Excellence, the Alumni Faculty Award and the Distinguished Alumni Award in ophthalmology.

Tom Kitchen

Beatriz Carreno, PhD, (left) and colleague Michelle Becker-Hapak, both of Washington University School of Medicine in St. Louis, deliver a personalized melanoma vaccine into an infusion bag. The vaccine was given to a patient with advanced melanoma via intravenous administration.

Personalized melanoma vaccines can be used to marshal a powerful immune response against unique mutations in patients' tumors, according to early data in a first-in-people clinical trial at Washington University School of Medicine in St. Louis.

The tailor-made vaccines, given to three patients with advanced melanoma, appeared to increase the number and diversity of cancer-fighting T cells responding to the tumors. The finding is a boost to cancer immunotherapy, a treatment strategy that unleashes the immune system to seek out and destroy cancer.

The research is reported April 2 in Science Express, in a special issue devoted to cancer immunology and immunotherapy. 

In a new approach, the cancer vaccines were developed by first sequencing the genomes of patients' tumors and samples of the patients' healthy tissues to identify mutated proteins called neoantigens unique to the tumor cells. Then, using computer algorithms and laboratory tests, the researchers were able to predict and test which of those neoantigens would be most likely to provoke a potent immune response and would be useful to include in a vaccine.

The vaccines were given to melanoma patients who had had surgery to remove their tumors but whose cancer cells had spread to the lymph nodes, an indicator the deadly skin cancer is likely to recur. These clinical findings set the stage for a phase I vaccine trial, approved by the Food and Drug Administration as part of an investigational new drug application. The trial will enroll six patients.

Robert Boston

Personalized melanoma vaccines developed at Washington University in St. Louis have been shown in a small clinical trial to marshal a powerful immune response against unique mutations in patients' tumors. Pictured are Gerald Linette, MD, PhD, and Beatriz Carreno, PhD, who led the team that developed the vaccines.

Data on the immune response seen in the first three patients is reported in the paper. If additional testing in more patients indicates the vaccines are effective, they may one day be given to patients after surgery to stimulate the immune system to attack lingering cancer cells and prevent a recurrence.

"This proof-of-principle study shows that these custom-designed vaccines can elicit a very strong immune response," said senior author Gerald Linette, MD, PhD, a Washington University medical oncologist leading the clinical trial at Siteman Cancer Center and Barnes-Jewish Hospital. "The tumor antigens we inserted into the vaccines provoked a broad response among the immune system's killer T cells responsible for destroying tumors. Our results are preliminary, but we think the vaccines have therapeutic potential based on the breadth and remarkable diversity of the T-cell response."

It's too early to say whether the vaccines will be effective in the long term, the researchers cautioned. The study was designed to evaluate safety and immune response; however, none of the patients has experienced adverse side effects.

Earlier attempts at vaccines have focused on targeting normal proteins commonly expressed at high levels in particular cancers. Those same proteins also are found in healthy cells, making it difficult to stimulate a potent immune response.

The new approach investigated by the Washington University team merges cancer genomics with cancer immunotherapy.

"This is about as personalized as vaccines can get," said co-author Elaine Mardis, PhD, co-director of the McDonnell Genome Institute at Washington University, where the cancer genome sequencing, analysis and neoantigen prediction were performed. "The approach we describe is fundamentally different from conventional mutation discovery, which focuses on identifying mutated genes that drive cancer development. Instead, we're looking for a unique set of mutated proteins in a patient's tumor that would be most likely to be recognized by the immune system as foreign."

Melanomas are notorious for having high numbers of genetic mutations caused by exposure to ultraviolet light. Biopsy samples of melanomas typically carry 500 or more mutated genes. Using prediction algorithms, the researchers narrowed their search for vaccine candidates by identifying neoantigens that not only were expressed in a patient's tumor but also were likely to be seen by that patient's immune system as "non-self."

Robert Boston

Elaine Mardis, PhD, of the McDonnell Genome Institute at Washington University. The genome sequencing, analysis and neoantigen prediction that led to the personalized melanoma vaccines were performed at the institute.

Biochemical validation of neoantigen peptide expression on the cancer cells' surfaces was performed in collaboration with William Hildebrand's group at the University of Oklahoma Health Sciences Center and provided critical assurance that the vaccine would elicit the most effective T cells to combat the melanoma.

"You can think of a neoantigen as a flag on each cancer cell," said first author Beatriz Carreno, PhD, associate professor of medicine. "Each patient's melanoma can have hundreds of different flags. As part of validating candidate vaccine neoantigens, we were able to identify the flags on the patients' cancer cells. Then we created customized vaccines to a select group of flags on each patient's tumor."

Carreno and her colleagues selected a set of seven unique neoantigens for each vaccine and used specialized immune cells called dendritic cells, derived from the patients, to carry those neoantigens to the immune system. Dendritic cells play an important role in waking up the immune system, reminding T cells to attack the cancer.

After the vaccine infusions, the patients' blood was drawn every week for about four months. By analyzing the blood samples, the researchers could see that each patient mounted an immune response to specific neoantigens in their vaccines. The vaccines also stimulated diverse clones of battle-ready T cells against neoantigens, suggesting this approach also could be used to activate a range of T cells and target them to mutations in other cancers with high mutation rates, such as lung cancer, bladder cancer and certain colorectal cancers.

"Our team has developed a new strategy for personalized cancer immunotherapy," Linette said. "Many researchers have hypothesized that it would be possible to use neoantigens to broadly activate the human immune system, but we didn't know that for sure until now. We still have much more work to do, but this is an important first step and opens the door to personalized immune-based cancer treatments."

Siteman Cancer Center, the only National Cancer Institute-designated Comprehensive Cancer Center in Missouri, is ranked among the top cancer facilities in the nation by U.S. News & World Report. Comprising the cancer research, prevention and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine, Siteman is also Missouri’s only member of the National Comprehensive Cancer Network.

Christopher A. Maher, PhD, assistant professor of medicine at Washington University School of Medicine in St. Louis, has received a three-year, $450,000 Susan G. Komen Career Catalyst Award for research focused on understanding the role of long noncoding RNAs in estrogen-positive breast cancer treatment resistance. Maher's lead mentor is Elaine R. Mardis, PhD, the Robert E. and Louise F. Dunn Distinguished Professor of Medicine.

E. Holland Durando

Beatriz Carreno, PhD, associate professor of medicine, prepares to go on the air with "Science Friday," the syndicated radio show broadcast on National Public Radio affiliates. From a School of Medicine studio, she was a featured guest on the show Friday, April 3. 

In the past six months, Washington University School of Medicine faculty have made four appearances on "Science Friday," the award-winning radio show hosted by Ira Flatow and broadcast on public radio stations nationwide.

On Friday, April 3, Beatriz Carreno, PhD, became the latest when she discussed research involving the use of personalized melanoma vaccines to marshal a powerful immune response against unique mutations in patients’ tumors. The findings the associate professor of medicine talked about stem from early data in a first-in-people clinical trial at the School of Medicine. Visit the Science Friday website to hear the broadcast.

Other recent "Science Friday" shows that focused on Washington University research featured:

• Audrey Odom, PhD, MD, assistant professor of pediatrics and of molecular microbiology, talking March 27 about her research into how the malaria parasite attracts mosquitoes with perfume of sorts;

• Wes Warren, PhD, associate professor of genetics, who went on the air Nov. 14 to discuss an analysis of the cat genome led by researchers at the School of Medicine;

• And, in keeping with Halloween, Sanjeev Bhalla, MD, professor of radiology and chief of cardiothoracic imaging, talking Oct. 31 about a university research team’s scans of three Egyptian mummies. The effort to uncover information about the mummies without uncovering the mummies themselves was a collaboration of the School of Medicine, the university’s Mildred Lane Kemper Art Museum, and the Saint Louis Art Museum.

Over the next several months, construction projects at and near Washington University Medical Center will continue to affect traffic flow and shuttles as improvements to parking and intersections continue.

Follow this link for a map indicating shuttle and other changes. Below is a timeline of upcoming events.

Effective April 20

Duncan/Newstead intersection to reopen, Duncan to close west of Newstead

The intersection at Duncan and Newstead avenues will reopen April 20. Duncan west of Newstead will close as work to upgrade the Metropolitan Sewer District (MSD) storm water line continues. This section of Duncan is expected to be closed for three weeks.

While this section of Duncan is closed, the entrance and exit to the St. Louis Children’s Hospital staff garage on Duncan will be closed. Additionally:

• All who use the SLCH staff garage will have to enter and exit from Newstead.
• The SLCH shuttle stop in the garage will be relocated to the parking lot of 4444 Forest Park Ave. The 4444 building will be open and staffed with a security officer beginning at 4 a.m. Monday through Friday and ending at 1 a.m. each of those days so staff will have the option of waiting inside the building.
  
• Pedestrian access across Duncan will be maintained at all times.

Shuttle depot to close, stops to relocate

Site work will begin for the new administrative office building at 4570 Children’s Place, which will require the closure of the shuttle depot between the Eric P. Newman Education Center and the MetroLink stop. The following shuttle stops will be available until the new building opens in 2017:

• On the south campus, a new stop at West Pavilion (near the patient drop-off area in front of Barnes-Jewish Hospital);
•  On the south campus, the existing stop at Olin Hall Circle on McKinley Avenue;
• At SLCH and north campus, at Wohl Circle;
• On the north campus, the existing stop at the Center for Outpatient Health.

With the addition of shuttle traffic on Children’s Place and Wohl Circle, security will monitor the circle drive in front of SLCH. Cars will not be allowed to park for more than five minutes.

Effective mid-May

Upon completion of the MSD work on Duncan:

• Duncan will reopen to traffic in both directions.
  
• The entrance/exit to the SLCH garage will reopen.
• The Newstead entrance/exit to the SLCH staff garage will close for up to two months as the access road to the new garage is constructed and this entry drive is reconfigured to accommodate the new and existing garages.
• The shuttle stop for SLCH parkers will remain at the 4444 building.
  

Public safety officers will continue to monitor traffic flow and direct vehicles.

Questions regarding shuttles can be directed to Margie Brine, 314-362-0760 or mbrine@bjc.org.