New medstudentsarrivefromnearandfar California. announced her home town: Weitchpec, of Medicine’s whitecoatceremony and to themicrophone during theSchool Volume 11, No.16 W By MandyErickson causing deadlylungdisease, study shows Inflammation maytriggersilentmutation, sure in the lungs. adeadlyformofhighbloodpres hypertension, - nary genetic defectthatcausessuddenonsetcasesofpulmo- something assimpletheflu,maywakeupasilent that inflammationinthelungsofrats,triggered by By Tracie White includesthefollowing sentences:The affirmation ofhumanity. “Ipledgetodevotemylifetheservice Thecare ofmypatientswillbefirstconsideration.” New medicalstudentsread on theStanford Affirmation Aug. 23atthewhitecoatceremony, andKnowledge. heldnext totheLiKaShingCenterforLearning “It’s akindofone-twopunch,” saidAmy Tian, PhD, Researchers attheSchoolofMedicine have found pelt, Melissa Eidman strode up abalone shellearringsandamink earing ared dress, abasketcap, INSIDE STANFORD MEDICINE September 9, 2019 9, September CHINGYUNSONG/SHUTTERSTOCK.COM tion to care for its residents. she plans toreturn tothe Yurok- reserva but onceshe’s afullytrainedphysician, loom. Eidman grew upinSacramento, traditional garb;thepeltisafamilyheir- tors, the Yurok Tribe. Her accessories are western corner, is the home of her ances- “I’m excited andhonored tobewear- Weitchpec, inthestate’s- farnorth 30% survival rate. rate. 30% survival of the disease is lung transplantation, but it has only a of America. The onlyavailable cure forsevere forms according tothePulmonary Hypertension Association are hospitalized with the disease in the United States, climbing aflightofstairs.About 200,000peopleayear simple daily activities,suchasweakened toperform ing, fatigueandchestpain. It canleave patients too sion, adebilitatingdiseasethatcausesdifficultybreath- hypertension.”in pulmonary the scientificunderstandingofrole ofinflammation tions deadly,” Nicolls said.“It advances the alsofurther ‘second hits’ can render ordinarily silent genetic muta icine, is the senior author. and criticalcare med- professor andchiefofpulmonary published Aug. 29inCirculation. Mark Nicolls, MD, to this terrible disease. ” sudden you getabacterialorviralinfection,anditleads thismutation,andallofthe be healthyandcarrying ofthelungs. hit isinflammationinthearteries You can “Basically, the first hit is the mutation, and the second andcriticalcare.senior research scientistinpulmonary PublishedbytheOfficeofCommunication&PublicAffairs - There hyperten isnoknown causeofpulmonary research isimportant forunderstandinghow“This Tian istheleadauthorofstudy, whichwas white coatsattheAug. 23ceremony out- long haul,” she said. community college.“It’s beenquitea dergraduate afterspendingyears ata Stanford isn’t: She transferred as an un- it. The coatisnew, butforEidman, which hadhernameembroidered on ing it,” Eidman saidofthewhitecoat, See Ninety medicalstudentsdonned HYPERTENSION, page6 - who holdsthe Violetta bance of our gut bacteria,” he said. to vaccination — directly induced through the distur mune response inhumans —inthiscase,ourresponse of the effects of broad-spectrum antibiotics on the im Medicine. immunology attheSchoolof ogy and of microbiology and dran, PhD, professor ofpathol- or vaccines, said Bali Pulen viously unencountered germs lenges, suchasexposure topre- able torespond chal- tonew leave theimmune systemless teria by antibioticsappearsto of the flu vaccine. ics mayreduce theeffectiveness By BruceGoldman according toscientists affected by gutbacteria, Response tofluvaccine A new studyinhealthyadultssuggeststhatantibiot- A new The studywas publishedSept. 5in Cell. Pulendran, “To our knowledge, this is the firstdemonstration The depletionofgutbac- STEVE FISCH planet,” Dean the mostaccomplishedpeopleon said Alexander overwhelming senseofaccountability,” bility thatthewhitecoatcarries—“an “But tangible.” this coat makes it all very Samson Peter ofSan Mateo, California. has been abstract for a long time,” said high school.” cago. “It’s somethingI’ve aspired tosince medical student from Sudan and Chi- feels really surreal,” saidIbtihal Elfaki, a to getusedwearing thewhitecoat.“It and 8% who are LGBTQ. who were bornoutsidetheUnited States under-represented inmedicine,34% with 26%whoidentifyasanethnicity the mostdiverse inStanford’s history, other places. The classof2023isamong stan, Venezuela andEngland, among City, California,aswell asfrom Kazakh- York; Houston; andnearby Redwood from them.” towardness to run crises and not away stethoscope, you’re showing your willing- mony. you receive “When your coat and medicalstudentsattheircerethe new - Alumni Association. scopes, giftsfrom theStanford Medicine programs. the beginningofstudents’ respective put on white coats. The events marked in the physician assistant program also studentsearlier that afternoon, 28 news and Knowledge. In aseparateceremony side theLiKaShing CenterforLearning Diverseclass “By allaccounts, you are among They alsofelttheburden ofresponsi- ideaofbeingamedicalstudent “The Many students said they would need The medical students hail from New All studentsalsoreceived stetho- Lloyd Minor - See See CEREMONIES, page4 Bali Pulendran Page 5 health care. add value to initiatives that spotlights magazine Medicine of issue The new BACTERIA, page7 Stanford , MD, told

- - Researchers enhance neuron recovery in rats after blood flow stalls

By Jonathan Wosen Amid the damage, levels of a microRNA known port cells known as astrocytes moved into the dam- as miR-181a soar. In an earlier study, the researchers aged region. Typically, astrocytes sit above and below Researchers at the School of Medicine report in a blocked miR-181a with a molecule designed to stick to the neuron-containing layer of the CA1 and support new study that they found a way to help rats recover and inactivate the microRNA. They found that block- the metabolism and connectivity of their neuronal neurons in the brain’s center of learning and memory. ing miR-181a before reducing the flow of blood to the neighbors. They accomplished the feat by blocking a molecule that brains of rats stopped neurons from dying. To figure out what the astrocytes were up to, the controls how efficiently genetic instructions are used to “If you want to find a therapy for an injury, one scientists tracked them with fluorescent molecules that build proteins. approach is to look for disruptions that occur in cells labelled astrocytes green and neurons red. When they If the approach described in the study could be ap- and try to reverse them. The first step was asking, ‘Is re- looked under the microscope, they found cells that plied to humans, it may one day help versing the increase in this specific microRNA glowed yellow — meaning the cells expressed both patients who’ve suffered a stroke, cardiac protective?’” Stary said. green and red markers. These yellow cells were found arrest or major blood loss and are thus at But while the prior findings were encour- at higher levels in rats in which miR181a had been higher risk of memory loss. aging, they didn’t reflect how such an inter- blocked. In the study, published online Aug. 19 vention would probably be used in a clinical The observation strongly implied that some of the in eNeuro, researchers induced extremely setting; it’s more likely that a patient would astrocytes were beginning to turn into neurons. While low blood pressure — as would happen receive a microRNA blockade after an injury. the researchers are planning further experiments to con- when the heart stops beating — in rats. To test whether miR-181a blockade helped firm the finding, astrocytes have been shown to turn These rats lost neurons in a specific region rats recover hippocampal neurons, the re- into neurons in other animal models of brain injury. of the hippocampus critical to learning searchers decreased the rats’ blood pressure Whether this phenomenon occurs in humans after and memory, but the researchers im- Creed Stary dramatically by siphoning off much of their loss of blood flow to the brain has not yet been fully proved the animals’ recovery of the cells blood and reinfusing it 10 minutes later. Simi- established, but if verified, it could open a new realm of by injecting a molecule that blocks a microRNA: a short lar drops in blood pressure can occur in people during astrocyte-based gene therapies for survivors of cardiac molecule that tweaks gene activation by preventing the cardiac arrest, after a major loss of blood or during cer- arrest and stroke. conversion of genetic blueprints into proteins. Interest- tain surgeries. The researchers next plan to verify whether block- ingly, the scientists found that a microRNA blockade The blood pressure drop caused nearly 95% of neu- ing miRNA-181a helps the rats recover their memory, potentially causes astrocytes — cells that support neu- rons in a region of the hippocampus known as CA1 learning and other cognitive abilities linked to the hip- rons and make up 50% of cells in the brain — to turn to die off. By around two months after the procedure, pocampus. If so, the approach is one step closer to into neurons. those neurons bounced back to nearly aiding recovery from brain The findings demonstrate that neurons, with some 50% of normal levels. injuries in which blood flow assistance from their astrocyte neighbors, recover in a The researchers then tested the ef- “There’s currently no gets cut off. region of the hippocampus not known to have a local fects of a microRNA blockade by in- “This paper shows that stem cell population that can replenish lost neurons. jecting the blocking molecule directly treatment to improve you can effectively augment Enhancing this recovery in humans could help those into the hippocampus of rats either brain function in patients the normal recovery the who’ve suffered a temporary loss of blood flow to the two hours or seven days after the brain tries to do on its own brain. animals experienced a drop in blood with heavy blood loss, by blocking this specific mi- “There’s currently no treatment to improve brain pressure. These rats had significantly cardiac arrest or stroke.” croRNA across injury models function in patients with heavy blood loss, cardiac arrest higher neuronal recovery than those and across species, something or stroke,” said Creed Stary, MD, PhD, assistant profes- injected with a control molecule that of a holy grail for a gene sor of anesthesiology, perioperative and pain medicine. didn’t target any known microRNAs. In earlier studies, therapy,” Stary said. “It points toward blocking the “This is the first study to show that the natural process the researchers showed they could deliver the blockade microRNA being a protective agent itself, but also pro- of post-injury hippocampal recovery can be substan- intravenously, making it well-suited for clinical use. vides insight to identify new therapeutic gene targets, tially improved with a pharmaceutical microRNA-based Solving a puzzle opening the possibility for combinatorial or adjuvant therapy.” pharmaceutical therapies.” Stary is the study’s senior author. Lead authorship But the fact that there was any recovery was puzzling. Stary is a member of Stanford Bio-X and the Wu Tsai is shared by postdoctoral scholar Brian Griffiths, PhD, The hippocampus is one of the few brain regions that Neurosciences Institute at Stanford. and senior research scientist Yi-Bing Ouyang, PhD. harbors neural stem cells, which can form new neurons Other Stanford co-authors of the study are research Under (low blood) pressure in adults, but not in the CA1 region the researchers associates Lijun Xu, MD, and Xiaoyun Sun, MD; and were studying. Rona Giffard, MD, PhD, professor emerita of anesthe- When fresh blood stops flowing through the brain, “If you don’t have new neural stem cells and you siology, perioperative and pain medicine. cellular waste piles up, and neurons starved of oxygen don’t have any evidence of cell division, then how are This study was supported by the American Heart As- and glucose eventually die. This can occur when a per- CA1 neurons being repopulated?” Stary said. sociation and the National Institutes of Health. son has a stroke, loses a significant amount of blood or The researchers had one important clue: When CA1 Stanford’s Department of Anesthesiology, Periopera- suffers a cardiac arrest. neurons were at their nadir, specialized neuronal sup- tive and Pain Medicine also supported the work. ISM

Mildred Cho to co-lead new coordinating hub for biomedical ethics

By Patricia Hannon genomics. Cho said the mission of the ELSI with a new web portal for ELSI con- The effort will be led by Mildred center is to build a community around tent that will be identified, collected The Stanford Center for Biomedical Cho, PhD, associate director of the conducting, sharing and using ELSI re- and shared. Cho expects that content Ethics has been chosen by the National Stanford Biomedical Ethics Center, and search, and to make that collection of to come from such sources as scientific Human Genome Research Institute to Sandra Soo-Jin Lee, PhD, chief of the material accessible and understandable and academic research, news stories and help develop a coordinating hub for in- Division of Ethics and faculty in Colum- to experts and the public. commentary, scientific journals, laws formation on the ethical, legal and social bia University’s Department of Medical Almost 30 years after the and legal briefings. implications of genetic research. Humanities and Ethics. The Hastings launch of the International Through such data collec- The new Center for ELSI Resources Center, a bioethics research organiza- Human Genome Project, tion, the center’s leaders hope and Analysis is being funded with a $7.1 tion, and Harvard University, which which aimed to map the to gain a better understand- million award, the institute announced houses the Personal Genetics Educa- human genome, many ethi- ing of gaps in knowledge and Aug. 14. ELSI is an abbreviation for the tion Project, will collaborate on the new cal and legal concerns still to communicate those gaps to ethical, legal and social implications of center. surround genetic research, researchers. They also hope to Cho noted. Yet there’s no help influence scientific inves- Inside Stanford Medicine is central repository where tigation by facilitating collab- published monthly in July and people grappling with such orations between researchers Mildred Cho STANFORD December and semi-monthly issues can easily find ethical and by holding a separately

INSIDE the rest of the year. or policy guidance, or pub- funded biennial congress to MEDICINE lished research, or connect with experts bring them together. is produced by Susan Ipaktchian who can help guide them. But central to center’s aim is to share Office of Communication & Public Affairs Director of print & Web communications “I think it should be easier for peo- ELSI knowledge with people who might Stanford University ple who are writing legislation that has not be aware it’s available, and to tailor School of Medicine John Sanford 455 Broadway, 4th floor Editor to do with consumer genetic testing, the information for specific stakeholders Redwood City, CA 94063 Robin Weiss or the release of data from Ancestry. — policymakers, medical professionals, Mail code 5471 Graphic designer com, to be able to find experts who are journalists, teachers, the general public (650) 723-6911 knowledgeable about the implications of and even scientists themselves. This is http://med.stanford.edu/news/ data collection by genomic companies,” important, Cho said, because ELSI con- said Cho, professor of pediatrics and of tent draws from a number of disciplines, Send letters, comments and story ideas to John medicine. including philosophy, sociology, psychia- Sanford at 723-8309 or at [email protected]. try, economics and politics. Please also contact him to receive an e-mail Filling a void version of Inside Stanford Medicine. “We’re going to try to develop new The center is poised to fill that void methods for synthe- See ETHICS, page 3 2 SEPTEMBER 9, 2019 INSIDE STANFORD MEDICINE 5 questions On using ‘real-world data’ to inform clinical care an occasional feature in which an expert answers five questions on a science or policy topic Electronic health records have paved the data science and of surgery at the School of Medicine. So she and a team of scientists set way for a new approach to biomedical research: the analysis of real-world data. The term up a case study to determine how accurately algorithms trained on real-world data can “real-world data” comes from the idea that EHRs aren’t just health histories of single predict the answer to medically relevant questions. In the case study, Hernandez-Boussard individuals; they’re a trove of information that can help guide clinical decisions, from and a team of scientists posed a simple question: How well can an EHR-trained algo- diagnosis to treatment. rithm predict if a patient has a cardiovascular condition? In 2016, the 21st Century Cures Act became federal law. It helped bring about a In a paper published Aug. 15 in the Journal of the American Medical Informatics new focus on harnessing real-world data in medicine, as opposed to letting clinical trials Association, Hernandez-Boussard, lead author of the study, shows that the answer is very be the sole guiding source. Today, doctors and scientists are increasingly turning toward well — and also not so well. It turns out the accuracy of the prediction depends on how algorithms trained on EHRs to guide diagnoses and determine treatment options for the data is organized and gathered. patients. Science writer Hanae Armitage spoke with Hernandez-Boussard about the value of The problem is that EHRs can be quite messy, making data extraction complex, said real-world data, how it fits into the current clinical care landscape and what her study Tina Hernandez-Boussard, MD, PhD, associate professor of medicine, of biomedical revealed about harnessing this immense dataset.

What’s the most important contribution of real- note different diseases. We tend to think of this data different health care settings from different geographical world data to medical decision-making? 1 as more regularly curated, and therefore more accurate, locations. These diverse datasets are important to ad- HERNANDEZ-BOUSSARD: It’s really the generalizability but our case study showed us that the most rich infor- dress the generalizability of the technologies. that’s key; pulling from real-world data provides infor- mation is actually in the clinical narrative text, or un- mation that’s representative of the way most the popu- structured data — for example, the free text notes that a Why is there an increasing trend toward using real- lation receives their care. Real-world data doesn’t have clinician takes during a patient visit. 4 word evidence instead of, or in conjunction with, strict inclusion or exclusion criteria, so it means that So in our study we found that we were more accu- the clinical trial data to inform medical decisions? any clinical assertions made with that data can apply to rately able to identify different aspects of the population HERNANDEZ-BOUSSARD: There are a handful of rea- a typical patient seeking routine care. — like diseases or procedures they’d had done — when sons. First, clinical trials are pricey — we’re talking Very often “gold standard” clinical trials are looking using just the unstructured data. So for example, we millions and millions of dollars — and they only en- at a particular drug for a particular disease, and patients wanted to see if we could identify the pop- compass a very small portion of the popula- can end up excluded if they have conflicting comorbidi- ulation of patients who had coronary artery tion. Real-world data repurposes EHRs to ties, some of which can be quite common. So say, for disease. When we used structured data we guide clinical care at a fraction of the cost. example, there’s a trial for a cancer drug; it might ex- could do so with 80% accuracy. But when The second big criticism of clinical trials is clude a patient who has hypertension or diabetes. But we use the unstructured data, that jumped that they’re often not broadly generalizable. in reality, the patients with hypertension and diabetes up to 95%. The patients that are included in trials often might be the ones who really benefit from the drug. When we think about how clinicians do not fully represent the range of patients And so looser inclusion and exclusion criteria enables and patients interact, the clinician is an that could benefit from a new drug or therapy. us to see how this drug works, or doesn’t work, in much active listener and note taker, capturing Third, these clinical trials are highly con- broader populations and subpopulations of patients. much of their conversation in written nar- trolled. Patients come in for an appointment rative form. That’s where they’re likely able Tina Hernandez- or treatment and in, say, exactly two weeks Your team set up a case study to evaluate real- to provide the most details about the pa- Boussard they must come back for a follow-up or their 2 word data in the context of cardiovascular medi- tient, as opposed to structured data, which next dose of medication. But that’s not really cine. What did the study investigate and what were the fall more into the numbers and codes cat- the way that patients receive care. In reality, most significant takeaways? egory. So we end up getting richer, more accurate infor- patients aren’t always able to stick to a regimented cal- HERNANDEZ-BOUSSARD: With our case study, we set mation when we just analyze free text. endar. Maybe they’re on vacation and need to wait three out to see if and how real-world evidence could be weeks until they schedule their next appointment. used to guide clinical assertions, such as identifying a What were the limitations of using real-world data patient with a particular disease or guiding treatment 3 in your case study? How do you think real-world evidence can best fit options. It seems reasonable to expect that real-world HERNANDEZ-BOUSSARD: I would say that the technol- 5 into a clinical care context? data could help inform those clinical assertions, but this ogy to actually run the algorithms that harness real- HERNANDEZ-BOUSSARD: Clinical trial data still pro- data largely comes from electronic health records and world data is, in many ways, a limiting factor. For this vides the highest level of certainty for guiding clinical insurance claims. They’re not intended to guide care for study, we used state-of-the-art artificial intelligence care. But if, for example, you run a clinical trial, and others; they’re meant to capture information for billing technologies. And to be able to harness real-world data end up with a very low representation of a specific sub- and patient history purposes, and they’re really complex effectively is a key part, but not everyone has access to population, how would you know how well that drug and messy. So, any data we pull out of them has to be it or the expertise to conduct that kind of analysis. The works in that subpopulation? And that’s where we think done with great caution. We wanted to assess how ac- second limitation is actually having access to data on real-world data could fill in a gap. curately EHR-based algorithms are when predicting a a large scale while being compliant with privacy laws. We’re not suggesting that real-world evidence should cardiovascular condition. While we were able to conduct our study with the data replace clinical trials by any means — clinical trials are In general, we saw that people using this EHR data set from Verantos, a collaborator on the study, data silos still held as the gold standard. Instead, we see it as more are mostly accessing something called “structured data,” are a very real problem, and it’s not always easy to gain of a hybrid situation, with patient care benefiting from which are things like vitals and medical codes that de- access to such a large amount of data that encompasses both sides. ISM

Ethics Applications for Chan Zuckerberg Biohub continued from page 2 ing David Magnus, PhD, director of the Center for Biomedical Ethics fellowships open to residents, clinical fellows and the Thomas A. Raffin Professor sizing different kinds of knowledge of Medicine and Biomedical Eth- The Chan Zuckerberg Biohub, a medi- diatric pulmonary medicine at the Stanford that typically aren’t combined,” ics. In addition, researchers from cal research organization that collaborates School of Medicine. “The CZ Biohub Phy- Cho said. UC-San Diego and Case Western with Stanford, UC-Berkeley and UC-San sician-Scientist Fellowship Program aims to The center’s collaborators bring University will be involved. Francisco, is offering two- to three-year re- change that by providing medical doctors a wealth of expertise to the project, Cho said a number of new peo- search fellowships for medical residents and who have limited research experience with with much of the team’s work be- ple also will be brought in to work clinical fellows. the opportunity to pursue a basic research ing conducted virtually, rather than on the Stanford campus in various Biohub fellows will conduct research path, gain expertise and cultivate their pas- at a single roles, includ- under a faculty mentor at one of the three sion for advancing medical knowledge.” location. ing to build campuses or at a Chan Zuckerberg Biohub The program will award about six fel- Lee, a for- “We have the opportunity the web portal lab in San Francisco. They will also learn lowships per year. Applicants must hold an mer senior and develop about medical economics, grant writing, MD degree but not a PhD, and be enrolled research to have our fingers on the the backbone career development and ethics, as well as full-time in a medical residency or clini- scholar at pulse of ELSI research.” of its technol- various biomedical and clinical research cal fellowship at Stanford or UCSF. They Stanford’s ogy, website and subjects. will need to commit to at least two years Center database. The goal of the fellowship is to equip at 75% time with CZ Biohub and spend for Biomedical Ethics, and other “We have the opportunity to young doctors to incorporate research into at least 20% of their time seeing patients. Columbia faculty members who have our fingers on the pulse of their careers. The number of physician- The fellowship will begin July 1, 2020. specialize in ethics, genetics and ELSI research and understand scientists is in decline, largely because of The Biohub is accepting applications biomedical informatics will work where the field is going and where financial pressures on academic medical until Oct. 1, 2019; awards will be an- at their campus to build the ELSI it needs to go,” Cho said. centers. nounced in December. Fellows can expect community. They also will partner Cho also leads the Center for In- “Despite their important role in bio- to be paid a salary similar to the one they with Columbia’s Graduate School tegration of Research on Genetics medical discovery, fewer physicians are are receiving for their residency or current of Journalism to assess how journal- and Ethics at Stanford. It was estab- dedicating their professional lives to re- fellowship. Applicants can find more infor- ists might use the portal, and what lished in 2004 as one of several Hu- search,” said David Cornfield, MD, the mation and apply at https://www.czbio- tools and information they would man Genome Research Institute’s program’s co-director and a professor of pe- hub.org/psfp. ISM find useful in their reporting. Centers for Excellence in ELSI Other Stanford researchers will research and is based at Stanford’s contribute to the project, includ- Center for Biomedical Ethics. ISM INSIDE STANFORD MEDICINE SEPTEMBER 9, 2019 3 New adult hospital to host community open house Sept. 14-15 The new Stanford Hospital will officially open its food trucks and family activities. first and foremost our community’s hospital.” doors to patients in the fall, but on Sept. 14 and 15, “We are thrilled that our vision of expanding our Open house visitors will be able to take part in a local residents can get a sneak peek as part of a two-day world-class academic medical center has come to 50-minute multimedia experience of the new facility. community open house featuring a multimedia experi- fruition,” said David Entwistle, president and CEO They’ll have the opportunity to learn about the ro- ence and a health- and wellness-inspired street fair with of Stanford Health Care. “The new Stanford Hospital is bots that deliver supplies throughout the building, the

BRYAN HAUX/SKYHAWK PHOTOGRAPHY technology-rich patient rooms and operating suites, the safety features, original art and rooftop gardens. Ex- perts also will be on hand to answer questions about the building’s design and construction and the advanced patient care technologies. “The community open house events will be a once- in-a-lifetime opportunity for the general public to go behind the scenes of the new hospital before it opens,” said Maggie Pringle Grauer, chair of the Stanford Medi- cine Community Council. “We are creating an experi- ential tour that will give visitors a firsthand look at the delivery of modern medicine.” In the promenade between the original Stanford Hospital and the new building, there will be a street fair with interactive activities for all ages. Booths will feature demonstrations of the latest telehealth and virtual real- ity tools used in surgery and patient care. There also will be health and nutrition advice, a larger-than-life game of Operation, Stanford’s therapy dogs, face painting, a treasure hunt, balloons, live music and a teddy bear tri- age area, where kids can care for the stuffed animals and take them home. Visitors will also have the chance to view the Stan- ford VOICES digital mural project, a mosaic of more than 4,000 drawings completed by patients, staff and community members. The community open house will run 9 a.m.-5 p.m. Sept. 14 and 9 a.m.-3 p.m. Sept. 15. It’s free and open to the public, but pre-registration is required. Sign up at www.stanfordhealthcares.com. Free parking is available at the Stock Farm Parking Garage, with shuttle access to Local residents can get a sneak peek of the new Stanford Hospital at a community open house scheduled for Sept. 14-15. the hospital entrance. ISM

STEVE FISCH looking forward to the years ahead. Ceremonies “I’m eager to get back to being with pa- continued from page 1 tients,” said physician assistant student Alex Topmiller, who worked at a dermatology Noonan, a student in the physician assistant clinic before arriving at Stanford. “I can’t wait program. for the clinics.” ISM Speakers at both ceremonies acknowledged the students’ competitiveness, but cautioned that they must set that tendency aside if they are to learn and grow during their time at Stanford. “Now is the time to work together and help each other out,” Zachary Stone, a third-year PA student, said at the physician assistant ceremony. Kimberly DeBruler, a third-year medical student, warned the new MD students that they would fail along the way. She also encour- aged them to reach out to students who appear to be struggling. “Check on each other. Text that person who didn’t make it to the party, or who stopped coming to class,” she said. Compassion and science Faculty speakers reminded the students that caring for patients calls for compassion as well as scientific knowledge. Abraham Verghese, MD, professor of medicine and a bestselling author, told the physician assistant students that he learned the difference between heal- ing and curing from his own physician as- sistant when he was practicing in El Paso, Texas. When the physician assistant took him to the home of a young man dying of AIDS, he asked, “What are we doing here?” She re- sponded, “We’re not here to do anything. We’re just here to be with the patient.” He realized that their visit signaled to the patient that his caregivers would not abandon him. In the days before there was an effective treatment for AIDS, he said, “We could heal when we could not cure.” Arturo Molina, MD, president of the Stan- ford Medicine Alumni Association, described the relationship between physician and patient as “sacred.” He told the medical students that they would need to practice empathy. “You will see patients who have had their dreams shattered by illness,” he said. “They will remind you not to take anything for granted.” At the receptions after the ceremonies, as (Clockwise from top left) Dean Lloyd Minor addresses the new medical students. First-year medical students with Iris Gibbs (fourth from right), associate the new students started feeling more com- dean of MD admissions. New students in the physician assistant program participated in a white coat ceremony earlier in the day on Aug. 23. fortable in their new garb, they said they were 4 SEPTEMBER 9, 2019 INSIDE STANFORD MEDICINE Stem cell researcher Irving Weissman awarded Albany Prize NORBERT VON DER GROEBEN By Krista Conger for a wide range of diseases including leukemia, non-Hodgkin lymphoma and Irving Weissman, MD, director of severe combined immunodeficiency (also Stanford’s Institute for Stem Cell Biology known as “bubble boy” disease). and Regenerative Medicine, will receive The two will be presented with the the 2019 Albany Medical Center Prize in prize at a Sept. 25 ceremony in Albany, Medicine and Biomedical Research for New York. his pioneering work in stem cell and can- “Dr. Weissman’s groundbreaking cer biology, including the identification work in advancing our understanding of blood-forming stem cells and their of blood-forming stem cells and cancer role in blood cancers, as well as the dis- has transformed many aspects of mod- covery of a “don’t eat me” signal on the ern medicine,” said Lloyd Minor, MD, surface of many cancer cells that protects dean of the Stanford School of Medicine. them from being eliminated by the im- “The discovery of the ‘don’t eat me’ signal mune system. on cancer cells promises to lead to novel Weissman is a professor of pathol- clinical applications that will improve hu- ogy and of developmental biology at the man health. We congratulate Dr. Weiss- Stanford School of Medicine and is the man on this well-deserved recognition.” director of the Ludwig Center for Can- Adult stem cells are unique in that cer Stem Cell Research at Stanford. He they can both self-renew and make will share the $500,000 prize with Bert progenitor cells that give rise to all the Vogelstein, MD, who is the Clayton specific cell types in a particular tissue Professor of Oncology and Pathology at of the body. In 1988, Weissman was Johns Hopkins University’s Sidney Kim- the first to identify and isolate in mice mel Cancer Center and the director of the hematopoietic, or blood-forming, the Lustgarten Foundation Pancreatic stem cells that form all the cells of the Stanford’s Irving Weissman will share the 2019 Albany Medical Center Prize in Medicine and Biomedical Cancer Research Laboratory at Johns blood and immune system. In 1992, he Research with Bert Vogelstein of Johns Hopkins University for discoveries in stem cell and cancer biology. Hopkins. and his group found the human blood- Vogelstein is known for discovering forming cells. He and his group have that a protein called p53 functions as since painstakingly traced the cellular blood and solid cancers. Overexpression syndrome, occur in blood-forming stem a tumor suppressor and that its inacti- steps leading from a stem cell to each of CD47 is also implicated in fibrotic cells, apparently hitchhiking in these self- vation is critical to the development of of the many types of mature blood and diseases such as scleroderma and surgi- renewing cells to form disease clones. It’s many human cancers. He was also the immune cells in humans, and identified cal adhesions. Recently, Weissman iden- a fantastic feeling to join the group of first to demonstrate in colorectal cancer those that go awry in many blood dis- tified additional “don’t eat me” signals, highly accomplished past recipients of that disease progres- eases and cancers. each of which is expressed by particular the Albany Prize.” sion is a multistep The prize will be Weissman also types of cancers. The Albany Prize is funded by a $50 process resulting identified a mole- “I’m especially honored to share this million gift from New York City philan- from the sequential presented at a cule called CD47 award with Bert Vogelstein, whose work thropist Morris Silverman. It has been accumulation of Sept. 25 ceremony that exists on the I have followed for many years and awarded since 2001 to encourage and mutations in specific surface of nearly greatly admire,” said Weissman, who is recognize extraordinary and sustained cancer-associated in Albany, New York. every human can- the Virginia and D.K. Ludwig Profes- contributions to improving health care genes. Together, cer cell and pro- sor for Clinical Investigation in Cancer and promoting biomedical research with Weissman and Vogelstein transformed tects them from attack by immune cells Research. “Inspired by his earlier work translational benefits for better patient the understanding of cancer biology, can- called macrophages. An antibody target- on colon cancer, we were able to show care. In 2015, Karl Deisseroth, MD, cer genomics and disease initiation and ing CD47, which the researchers have that nearly all stepwise mutations that PhD, Stanford professor of bioengineer- progression, paving the way for earlier termed a “don’t eat me” signal, is in clin- lead to the development of leukemia and ing and of psychiatry and behavioral sci- diagnosis and more effective treatments ical trials in people with several types of blood diseases, such as myelodysplastic ences, received the award. ISM

Stanford Medicine spotlights efforts that add value to health care

By Patricia Hannon anonymous patient records to provide the ultimate Print copies of the magazine, which is also online consult when a physician is stumped by a patient’s at http://stanmed.stanford.edu, are being sent to Eugene Celis can name many family members condition, symptoms or treatment options. subscribers. Others can request a copy at (650) 723- who died before the age of 60 from heart disease or • Initiatives to battle physician burnout at Stan- 6911 or by sending an email to medmag@stanford. complications from diabetes, and that worried him. ford are aimed at increasing professional fulfillment edu. ISM But Humanwide, a yearlong pilot project at Stanford for doctors by improving their work experiences and that integrated detailed health data about him with building efficiency to promote better team-based care, helped Celis see his way toward a teamwork and work-life integration. different future. • A new emergency protocol at Stan- The project is emblematic of the initiatives ex- ford Hospital drastically cuts down on plored in the latest issue of Stanford Medicine maga- the time it takes to give stroke patients zine, which features ways that Stanford Medicine’s a lifesaving treatment that can mean the focus on value is addressing the needs of patients and difference between walking and not walk- clinicians. ing, and between living alone and relying In a letter introducing the issue, Lloyd Minor, on caregivers. MD, dean of the Stanford School of Medicine, writes • When the director of a key outpatient that shifting the focus of health care to detect disease clinic at Lucile Packard Children’s Hospi- earlier, strengthen patient-provider relationships and tal Stanford set out to determine whether deploy the latest health technology enhances value in it was possible to increase patient capacity medicine and demonstrates the power and promise of without compromising care, she turned to precision health. Stanford mathematicians for help. “Personalized medicine means we can modify care • Biobanks aren’t new, but a 2017 high- down to an individual’s genome,” he writes. “And a tech revamp of Stanford’s biobanking ap- better understanding of the social determinants of proach is bridging the gap between the latest health — everything from our behavior to our envi- biomedical research and patient care. ronment — means we have the opportunity and duty • Delivering bad news to patients and their to treat each person individually.” families is about the toughest part of a phy- The stories in this issue touch on projects that are sician’s job, but a new virtual reality training aimed at doing just that: program gives them tools that can help. • In the Humanwide project, clinicians and pa- Also in this issue, read about how the vi- tients worked together — using information from sion of a mesa in a scientist’s dream changed genetic screenings, at-home digital monitoring de- the course of research into hypertrophic cardio- vices and detailed wellness assessments — to better myopathy, a deadly heart condition. And learn prevent, predict and cure disease. about how scientists see promise in a study show- • The Stanford Clinical Informatics Consult ser- ing that use of the hormone vasopressin helps vice harnesses a trove of health data from millions of children with autism improve their social skills.

INSIDE STANFORD MEDICINE SEPTEMBER 9, 2019 5 o b it ua ry James Trudell, who helped make anesthetics safer, dies at 77

By Tracie White PhD in organic chemistry at Stanford in 1969. His early work eventually led him to what was While a student at Stanford, he studied under Carl a new approach 30 years ago: the use of molecular James Trudell, PhD, a Stanford Medicine chemist Djerassi, PhD, a chemistry professor at the time, modeling to study receptor sites, the binding struc- who spent 50 years hunting down molecular clues to who later became known as the father of the birth tures on the surface of cells involved in how drugs help make anesthetic drugs safer for patients, died control pill. They remained lifelong friends. Be- cause unconsciousness. He began collaborating with July 29 at his home in Woodside, California, with fore starting graduate school, Bertaccini in the early 1990s, his wife by his side. He was 77. Trudell served two years on the “It was important to him using this research to help cre- The cause was complications from acute myeloid aircraft carrier USS Randolph ate new anesthetics with fewer leukemia. as a photo and electronics of- that his basic research side effects, including liver Trudell was a professor of anesthesiology, periop- ficer during the Vietnam War. would make people’s toxicity and lowering blood erative and pain medicine at the School of Medi- He joined the Anesthesiol- pressure. cine, where he could be seen for most of his career ogy Department at Stanford lives better.” “Our research, the molecu- bicycling to his lab in the Grant Building. His many in 1969, just four years after lar mechanism of how anes- decades of research advanced the understanding of it was created. He initially studied the molecular thesia works, is a small niche in the world, but he how anesthetics work to limit pain and contributed mechanisms that made halothane, one of the first played a key role,” Bertaccini said. to the ongoing pursuit to make newer, better anes- modern-day general anesthetics, toxic to the liver. At At times, during their long collaboration, the two thetics with fewer dangerous side effects. the time, there were only 12 faculty members in the scientists would delve into the metaphysical ques- “He was very obviously fascinated with under- department; today there are 200, Pearl said. Trudell tions surrounding their search to understand how standing, as a chemist, how molecules work,” said met Lin, his future wife, when she came to work as a people become unconscious to begin with — what Ron Pearl, MD, professor and chair of anesthesiol- postdoctoral scholar in in his lab. scientists refer to as “the human off switch,” Bertac- ogy, perioperative and pain medicine and the Dr. Lin describes her husband as the consummate sci- cini said. “It’s a metaphysical question, this idea that Richard K. and Erika N. Richards Professor, who entist, for whom chemistry was more than just a job. all human beings have the same ‘off switch.’ What worked with Trudell since 1985. “How exactly do “He was a true scientist at heart,” Lin said. “He happens to the human soul when you are anesthe- they interact? How can we make them do things we followed his research wherever it took him. He was tized? These drugs are used thousands of times a day want them to do and not do things we don’t want never discouraged by any failure. He would just take throughout the world. People wake up and they are them to? It was important to him that a break and go to one of his many hob- still there. We know it works; we just don’t know his basic research would make people’s bies, and come right back to his work. “ how it works.” lives better.” Trudell was also an accomplished He continued: “Jim probably knows the answer Trudell’s fascination with chemistry athlete who enjoyed a variety of activi- now and is laughing at us.” began early in life when his parents gave ties, from rock climbing, paragliding and Trudell’s dogged pursuit toward solving these him a chemistry kit at the age of 9. His running marathons in his earlier years to mysteries continued throughout his illness. He passion for the work never waned, con- bicycling and sailing throughout his life. worked from his laptop while at the hospital under- tinuing until the day he died, with a lap- “We expected him to live to 100,” said going chemotherapy and a bone marrow transplant, top computer and molecular modeling longtime friend and Stanford colleague Bertaccini said. research papers still open on his desk, Edward Bertaccini, MD, professor of an- “His contributions continued to flow as we just said his wife, WeiQi Lin, MD, PhD. James Trudell esthesiology, perioperative and pain med- had spoken and set up calculations during the week “For 50 years, Dr. Trudell’s innovative icine. “This guy was in the best shape all before he died,” Bertaccini said. research played a major role in advancing the field of of his life. He was windsurfing up until 15 years ago Trudell co-authored more than 170 papers. He anesthetics and improving patient safety,” said Lloyd and always riding his bike.” was a member of Stanford Bio-X and the Wu Tsai Minor, MD, dean of the School of Medicine. “More Study of drug metabolism Neurosciences Institute at Stanford. than just an exceptional scientist, he also strength- In addition to Lin, Trudell is survived by his ened the Stanford Medicine community by serving Trudell’s early work involved studying how drugs brother Ronald Trudell and his sister Cher Trudell, as a caring mentor and thoughtful collaborator to so metabolize within the human body. After figuring both of Michigan. many.” out how the drug halothane causes liver failure, he Per his wishes, Trudell’s ashes were scattered out- Native of Michigan examined the same problem in other anesthetics. side of the Golden Gate Bridge, on the San Fran- Along the way, he discovered that anesthetics work cisco Bay, on an outgoing tide. Donations in his Trudell was born in Iron Mountain, Michigan, through specific protein interactions rather than in- memory may be made to the Department of Anes- in 1941. He graduated magna cum laude from the teractions with lipids, the fatty molecules in tissues, thesiology, Perioperative and Pain Medicine at Stan- University of Michigan before going on to earn a as was believed at the time. ford. ISM

STEVE FISCH Hypertension researchers hypothesized that an inflam- tor of medicine; research assistants Petra continued from page 1 mation-producing pathway may provide Dahms, Allen Tu, Eric Shuffle and Yesl the second “hit” that triggers the muta- Kim; biostatician Peter Maguire; Hassan Pulmonary hypertension occurs when tion to cause the disease in certain pa- Chaib, PhD, director of laboratory oper- the arteries that transport blood from the tients. To test the theory, the researchers ations; Roham Zamanian, MD, associate heart to the lungs mysteriously thicken developed a rat model with a mutation professor of medicine; Michael Snyder, and become increasingly clogged, in the BMPR2 gene. They followed the MD, professor and chair of genetics; and thereby weakening the heart, which rats for a year, and found that the ani- Marlene Rabinovitch, MD, professor of has to pump extra hard to get blood to mals remained healthy. Yet when the rats pediatric cardiology. flow through the body. After diagnosis, were injected with a virus carrying the Researchers at the University of most patients face a prognosis of just a 5LO enzyme that triggered temporary Michigan, Virginia Commonwealth few years of life before they die of heart lung inflammation, they developed pul- University, the Université Paris-Sud and failure. Some patients are born with the monary hypertension. Mark Nicolls is the senior author of a study that the Université Paris-Saclay also contrib- disease, but often it strikes in later life. “At first, the rats with this mutation found that a simple viral infection in the lungs uted to the study. Treatment is limited to vasodilators, were healthy, running around the cage,” of rats can become a lethal form of pulmonary This work was funded by the Na- drugs that cause the smooth muscle cells Tian said. “Then we administered the hypertension if a common mutation is present. tional Institutes of Health and the Vera of the diseased blood vessels in the lungs virus into their lungs, which stimulated Moulton Wall Center. to relax, permitting more blood to flow the production of inflammation in the died, the damage to the endothelial cells Nicolls and Tian are co-inventors on through. These drugs help to extend sur- vessels of the lung, and they got really in the lining of the blood vessels contin- a patent titled “Treatment of Pulmo- vival and relieve some symptoms, but sick.” ued. The cells become the bad player, nary Hypertension with Leukotriene they are not a cure. Thus, scientists have The lung inflammation caused by the and they continued to proliferate the Inhibitors.” been searching for virus usually lasts inflammation.” Nicolls is a member of the Stanford other therapies. only a few weeks These results indicate that limiting Cardiovascular Institute. Past research and, in humans, can potential environmental causes of lung The Stanford Department of Medi- has shown that “It’s a kind of also be caused by inflammation in patients with a genetic cine also supported the work. ISM the majority of one-two punch.” environmental trig- risk for pulmonary hypertension may patients with the gers, such as a severe help prevent the development of the dis- inherited form of flu or bacterial infec- ease, the study said. pulmonary hy- tion or even hiking Other Stanford co-authors of the pertension, which is also the most lethal, to high altitudes. However, in the ge- study are Xinguo Jiang, MD, PhD, TAKE PART IN carry a mutation in the gene BMPR2. netically susceptible rats, the virus led to project leader; Yon Sung, MD, clinical CLINICAL RESEARCH Whether the mutation plays a role in permanent inflammation, damaging the assistant professor of pulmonary and causing the disease has been unclear. Sur- lung vessels and causing a lethal form of critical care medicine; medical student Stanford Medicine research- prisingly, 80% of people with the mu- pulmonary hypertension. Ting-Hsuan Wu; Peter Kao, MD, PhD, ers are recruiting participants tation don’t get the disease and remain “Asthma, a bad flu, temporary types associate professor of pulmonary and of all ages for a variety of clinical trials. perfectly healthy, Nicolls said. of lung injury from bacterial or virus in- critical care medicine; research scientists They need people with specific health fections — all can be 5LO-mediated,” Aiqin Cao, PhD, and Lingli Wang, MD; conditions, as well as healthy participants. A hypothesis For more information about clinical trials at Tian said. “This type of inflammation research assistant Patrick Zhang; former Stanford, visit clinicaltrials.stanford.edu. Based on previous research into in- normally has a pretty short life span. But postdoctoral scholar James Chappell, flammation in the lungs, the Stanford in these rats, even after the injected virus PhD; Shravani Pasupneti, MD, instruc- 6 SEPTEMBER 9, 2019 INSIDE STANFORD MEDICINE o b it ua ry Stanley Schrier, founding member of hematology division, dies

By Tracie White ure in the Department of Medicine,” hematologists. matology as a medical student,” Gotlib said Robert Harrington, MD, chair of “He was larger than life, a maestro said. “He was able to translate blood Stanley Schrier, MD, a founding the department, which houses the he- of hematology,” said Ranjana Advani, smears at the microscope into what pa- member of the Division of Hematol- matology division. “He was considered MD, professor of medicine and the tients were experiencing at the bedside. ogy at the Stanford University School a ‘doctor’s doctor,’ as well as an excep- Saul A. Rosenberg, MD, Professor in He had a boyish sense of wonder that of Medicine whose research advanced tional investigator, educator, mentor Lymphoma, who worked with Schrier never faded.” the field of red blood cell biology, died and leader.” for 30 years, first as a fellow and later a He also knew how to entertain his Aug. 16. He was 90 years old. Early appetite for science colleague. “He shaped my career from students, using his wit and storytelling Schrier continued to treat patients day one and continued to be a mentor skills to teach both a love of research and conduct research until just two Schrier grew up in the Bronx, New till the very end. He was like a father and how to show compassion for pa- months before his death, said Ravi Ma- York, where as a child his mother rec- figure. He’s going to live in my heart tients, Gotlib said. jeti, MD, PhD, professor of medicine ognized his love for science and encour- forever.” “He liked to sit down with his pa- and chief of the hematol- aged him to attend the Bronx Schrier’s research focused on the tients, not stand, and maintain eye con- ogy division. High School of Science, study of the biology of red blood cells. tact, maybe hold their hands,” Gotlib “He had a full clinic where he was admitted in In 1982, he began a more than 20-year said. “He taught us it’s OK to shed a up until July,” Majeti said. 1943, said his wife, Barbara study of thalassemia, a hereditary blood tear as long as you show you’re going “He was beyond a legend. Klein. disease widespread in Mediterranean, to be there with your patient through It’s so sad to think he’s “His parents were immi- African and Asian countries and among their journey. It’s hard for me to believe gone.” grants from Hungary,” Klein the most common genetic diseases in that future fellows won’t have the ben- Schrier was known not said. “They were poor but the world. efit of interacting with Stan. However, only for his research skills, rich in spirit. His mother saw He conducted research projects in we can sustain his legacy by nurturing but as a compassionate, she had a really bright son.” Israel, Italy and Thailand — countries what he imbued in all of us — excel- caring physician to thou- As an undergraduate, he with high rates of thalassemia — and lence in patient care, teaching and Stanley Schrier sands of patients during transferred from New York was involved with the American Soci- scholarship.” his 60 years at Stanford University to the University ety of Hematology’s volunteer outreach Schrier received numerous teach- and for his talent for teaching and of Colorado-Boulder after spending a programs in Uganda, Peru and Cam- ing awards, including the Albion Wal- training physicians and scientists. summer with relatives in Denver and bodia. He also served as president of ter Hewlett Award from the School “Dr. Schrier’s contributions to the falling in love with the mountains, she the American Society of Hematology of Medicine and the Walter J. Gores field of hematology and to Stanford said. in 2004 and helped initiate the orga- Award from Stanford University. Medicine are immeasurable,” said Schrier graduated from Johns Hop- nization’s doctor volunteer programs to In his spare time, he enjoyed making Lloyd Minor, MD, dean of the School kins School of Medicine in 1954, then improve care for various hematologi- wine with his son, David, and traveling of Medicine. “Not only was he instru- attended the University of Michigan cal disorders in developing countries. with his first wife, Peggy Schrier, who mental in developing Stanford Medi- and the University of Chicago for ad- He was editor of UpToDate, an online died in 2001, and their children, and cine’s hematology division, but he also ditional training. He served in the medical information service for physi- later with Klein and their grandchil- served as a trusted physician, innovative military as a member of the Commis- cians, and he had research grants to dren. He rode his bicycle to work at researcher, and committed mentor. We sioned Corps of the U.S. Public Health study anemia in elderly people when he Stanford until he was in his 80s. will miss Dr. Schrier’s unique and con- Service, conducting research into treat- died. In addition to Klein, he is survived tagious passion that inspired so many.” ments for Korean vivax malaria. The Sharing the patient’s journey by his two daughters, Rachel Schrier of Schrier joined Stanford as an in- malaria project sparked Schrier’s inter- San Diego, and Leslie Schrier of Foster structor in 1959, the same year the est in studying blood, his wife said. It was his passion for his work that City, California; his son, David Schrier school moved from San Francisco to When he arrived at Stanford, he spilled over into his teaching style and of San Carlos, California; and two the Palo Alto campus. He became a was one of just four members of the drew many into the field of hematol- grandchildren, Andres and Emilia. professor of medicine in 1972, then an division of hematology. In 1968, he be- ogy, said Jason Gotlib, MD, professor Private graveside services were held active emeritus professor in 1999. came division chief, a position he held of medicine at Stanford. Aug. 19 in Colma. A memorial event is “Stan Schrier was a remarkable fig- for 27 years, mentoring generations of “He made me fall in love with he- being planned. ISM

ROBERT KNESCHKE/SHUTTERSTOCK.COM Bacteria such as new viral strains represented in the seasonal flu continued from page 1 vaccine — than to those the immune system remem- L. Horton Professorship, is the senior author. Lead bered seeing before, Pulendran’s team recruited another authorship is shared by Stanford postdoctoral scholars 11 similarly aged participants for the 2015-16 season. Thomas Hagan, PhD, and Mario Cortese, PhD; and But this time, they selected only individuals whose low Nadine Rouphael, MD, PhD, associate professor of level of flu antibodies indicated low prior exposure to medicine and infectious disease at Emory University. the virus or to the vaccine itself. None of the new re- Inspired by a mouse study cruits had gotten flu vaccinations for at least the past three years. Five individuals got broad-spectrum anti- The idea that the trillions of bacteria inhabiting the biotics, as in the previous year. The other six served as human gut play a role in our health is far from new, but controls. All 11 got vaccinated. it hasn’t been rigorously proved. Hard data in humans Again, gut-bacteria counts in individuals who re- has been sparse, with causal evidence coming mainly ceived antibiotics plummeted, as in the previous year. from studies in mice. But this time there was a big change in levels of an anti- The new study was inspired by a mouse study that body subtype most responsible for countering the influ- Pulendran and his colleagues conducted in 2011. Those enza virus: This subtype failed to burgeon in the blood investigators found that mice raised from birth to have in response to the vaccine. Notably, the deficit in this Decimating levels of intestinal bacteria with antibiotics reduced germ-free intestinal tracts failed to mount as strong an antibody subtype correlated strongly with post-antibi- the immune system’s responsiveness to a seasonal influenza immune response to vaccination as their normal coun- otics decreases in total gut bacteria as well as in flagellin, vaccination, a study found. terparts. So did mice given antibiotics or bioengineered the bacterial protein, in volunteers’ stool samples — a to lack an immune sensor for flagellin, the chief protein proxy for microbial abundance in the gut. constituent of the threadlike flipper that bacteria use for Signs of inflammation to lose this resilience when confronted with a vaccine swimming around. containing new pathogenic elements of which they have “The question was, does this have any relevance to The recipients of the antibiotics exhibited many little or no prior memory.” humans?” Pulendran said. To try to answer this ques- signs of systemic inflammation — the same immu- The findings, Pulendran said, imply that when next tion, he and his associates conducted a study involving nological signature Pulendran has observed among season’s flu strain comes along, you want your gut-resi- 22 adults ages 18 to 45: During the 2014-15 flu season, people ages 65 and older after an influenza vaccina- dent microbes to be in full bloom in order for your im- 11 took broad-spectrum antibiotics over five days and tion in a prior study. The degree to which antibiotics mune system to rise to the occasion. Pulendran offered got a flu vaccine on day four; 11 others took no antibi- recipients’ immune systems exhibited this bodywide, some advice. “Get your annual flu shot,” he said. “The otics but got the flu vaccine on day four, as well. aging-associated systemic inflammation mirrored the greater your inventory of immune memory to influenza The antibiotics lowered the gut-bacterial population extent of depletion, in participants’ blood, of a series of strains bearing any resemblance to the one that’s com- by 10,000-fold. The resulting loss of overall diversity metabolites whose generation requires gut-bacterial as- ing over the hill, the more likely you’ll be able to deal was detectable for up to one year after the antibiotics sistance. These metabolites, called secondary bile acids, with it, even if your gut microbes are in short supply.” were taken. Still, 30 days after vaccination, vaccine- are known to dial down inflammatory processes in the Pulendran is a member of the Stanford Institute for induced increases in antibodies capable of preventing immune system. Intestinal bacteria fashion them from Immunity, Transplantation and Infection and a faculty influenza infection were comparable among the two primary bile acids initially produced in the liver. Levels fellow of Stanford ChEM-H. groups. of one important secondary bile acid, lithocholic acid, Other investigators at Emory University, as well as But the participants in this experiment tended to plunged by 1,000-fold in the bloodstreams of antibi- researchers at the Ragon Institute, the University of have pretty high levels of those antibodies to begin otic recipients, and was inversely correlated with the Chicago, Georgia State University and the Food and with, suggesting they’d already had some exposure to amount of inflammation. Drug Administration contributed to the work. the flu strains represented in the current or prior sea- “The study indicates that when it comes to respond- The work was funded by the National Institutes of sons’ vaccines. ing to vaccination against a previously encountered in- Health, the Soffer Endowment and the Violetta Horton To see if low counts of gut bacteria might pose a fectious pathogen, our immune systems are remarkably Endowment. greater obstacle to the immune system’s ability to re- resilient even in the face of the most severe depletion of Stanford’s departments of Pathology and of Micro- spond to previously unseen elements in a vaccine — our intestinal bacteria,” Pulendran said. “But they seem biology and Immunology also supported the work. ISM INSIDE STANFORD MEDICINE SEPTEMBER 9, 2019 7 p eo p le Melissa Bondy named chair of Epidemiology and Population Health Dept. Melissa Bondy, PhD, has been ap- ciplinary efforts to improve the health Prevention and Population Sciences advisory board for several NCI-desig- pointed chair of the Department of of individuals and populations through at Baylor College of Medicine’s Dan nated cancer centers. Last year, she re- Epidemiology and Population Health, the study of the distribution, determi- L. Duncan Cancer Center, ceived the visiting scholar formerly known as the Department of nants and control of illness and impair- where she focused much of award from the NCI Divi- Health Research and Policy. ment,” said Lloyd Minor, MD, dean of her research on understand- sion of Cancer Epidemiol- The appointment takes effect Oct. the School of Medicine. “We’re thrilled ing heredity patterns and ogy and Genetics. 1. that she has joined our faculty. Her ca- genetic susceptibilities in “My goal will be to try Bondy, who comes to Stanford from reer has exemplified the core tenets of brain and breast cancer. to find ways to genuinely Baylor College of Medicine, also will precision health.” “I’m excited to con- influence and improve serve in the newly created role of asso- Bondy earned a PhD in epidemiol- tinue my work at Stanford, the way we evaluate and ciate director for population sciences at ogy at the University of Texas School of and to further develop and inform health at a popu- the Stanford Cancer Institute. In that Public Health. Before coming to Stan- expand this new depart- lation level,” Bondy said. role, she will spearhead the research ford, she spent nearly two decades at ment,” Bondy said. “Part “To do that, we will har- enterprise of the institute’s population Baylor College of Medicine. In 2001, of that will be building an Melissa Bondy ness integrative epide- sciences program, which is designed she became director of the Childhood outstanding educational miology, with a focus on to reduce the burden of cancer and Cancer Epidemiology and Prevention program and increasing the number of genomics and digital approaches to improve outcomes for patients with Center, a joint center of Baylor College doctoral and postdoctoral students that monitor population health. I also look cancer. of Medicine, MD Anderson Cancer we bring in.” forward to collaborating not only with “Dr. Bondy is a renowned cancer Center and Texas Children’s Hospi- Bondy serves on the National Can- those in the department, but with re- epidemiologist whose leadership will tal. Ten years later, she took on a new cer Institute’s board of scientific advis- searchers from across the School of elevate Stanford Medicine’s multidis- role as the associate director of Cancer ers and is a member of the external Medicine and around the campus.” ISM

of note reports on significant honors and awards for faculty, staff and students

CHRISTOPHER ALMOND, MD, was promoted to pro- fessor of pediatrics, effective May 1. He directs clini- cal research in the Pediatric Advanced Care Therapies Program at Lucile Packard Children’s Hospital Stan- Christopher Almond Manual Amieva Leah Backhus Alistair Boettiger Leslie Mateo ford. His primary research interests are in multicenter clinical trials and learning health networks in pediatric heart failure, ventricular assist device support and car- $50,000 a year for up to three years to promote inclu- aims to optimize and individualize treatment for gyne- diac transplantation. sivity in laboratories and increase diversity in the life cologic cancers to improve disease control and quality MANUEL AMIEVA, MD, PhD, was promoted to pro- sciences. of life for patients. fessor of pediatrics and of microbiology and immunol- CATHERINE CURTIN, MD, was promoted to professor SHIVAANI KUMMAR, MD, professor of oncology and ogy, effective July 1. He specializes in treating pediatric of plastic and reconstructive surgery, effective July 1. radiology, was awarded the 2019 David R. Gandara infectious diseases. His research focuses on under- She specializes in peripheral nerve surgery and upper Lectureship on Developmental Therapeutics from the standing how bacteria colonize our skin and gastroin- limb reconstruction. Her research focuses on reducing UC-Davis Comprehensive Cancer Center. The award is testinal epithelium, and how that can lead to infection pain and improving function for people with peripheral for visionary leadership in developmental therapeutics and disease. nerve injury, and improving upper limb function for for cancer. LEAH BACKHUS, MD, associate professor of car- people with spinal cord injury. ROBBIE MAJZNER, MD, was appointed assistant pro- diothoracic surgery, received the Dr. Dwight C. Mc- LISA GIOCOMO, PhD, assistant professor of neurobiol- fessor of pediatrics, effective June 1. His research focuses Goon Award from the Thoracic Surgery Residents ogy, received a scholars award from the Vallee Foun- on optimizing chimeric antigen receptor T cell thera- Association for her commitment to teaching and men- dation. The $300,000 grant is for basic biomedical pies to treat neuroblastoma, sarcomas and brain tu- toring. She also received the Levi Watkins Innovation research. Giocomo researches the neural mechanisms of mors, particularly for pediatric cancer patients. and Leadership Development Scholarship from the cognition, specifically navigation. PHILIP PIZZO, MD, the David and Susan Heckerman Thoracic Surgery Foundation. The Watkins award in- JEREMY HEIT, MD, PhD, was appointed assistant Professor and professor of microbiology and immu- cludes $5,000 to cover travel expenses incurred for the professor of radiology, effective June 1. His research nology, received the New York Academy of Medicine’s purpose of learning new thoracic surgery techniques. uses neuroimaging techniques to study diseases affect- John Stearns Medal for Distinguished Contributions in ALISTAIR BOETTIGER, PhD, assistant professor of ing the blood vessels and blood supply to the brain, Clinical Practice. The award is for extraordinary, career- developmental biology, and LESLIE MATEO, a graduate with the goal of developing new minimally invasive long contributions to the clinical practice of medicine. student in developmental biology, were awarded a Gil- treatments for these diseases. ELSIE ROSS, MD, assistant professor of surgery, was liam Fellowship for Advanced Study. They will receive MARIE HOLLENHORST, MD, PhD, clinical instructor awarded a K01 grant from the National Institutes of of pathology, was awarded an early- Health. The five-year, $162,000-per-year grant will career scientist grant from the National support her study of artificial intelligence to enable Blood Foundation. The two-year, early identification and treatment of peripheral artery $75,000 grant will support her research disease. to understand how the sugar molecule BIRGITT SCHUELE, MD, associate professor of pathol- CMP-Neu5Ac is made and how it regu- ogy, was awarded a $100,000 grant from the Neuke- lates platelet number and function, with rmans Family Fund. The grant supports her research the goal of illuminating fundamental into neuronal microcircuits in Parkinson’s disease. aspects of platelet biology and develop- SHARON SHA, MD, associate professor of neurology ing effective therapies for bleeding and and neurological sciences, was appointed to the Al- Catherine Curtin Lisa Giocomo Jeremy Heit clotting disorders. zheimer’s Prevention and Preparedness Task Force for K.C. HUANG, PhD, was promoted the State of California. The task force presents recom- to professor of bioengineering and of mendations to the governor on how local communi- microbiology and immunology, effec- ties, private organizations, businesses, government and tive June 1. His research investigates families can prepare for the rise in the number of cases the physical mechanisms of cell growth of Alzheimer’s disease. and the ecological principles underly- KATHERINE TRAVIS, PhD, was appointed assistant ing microbial community assembly and professor (research) of pediatrics, effective July 1. Her function. research uses advanced neuroimaging techniques to ex- ELIZABETH KIDD, MD, was promoted amine how white matter structures of the brain con- to associate professor of radiation oncol- tribute to reading and language skills in children, with ogy, effective Aug. 1. Her clinical focus the goal of identifying and developing interventions for Marie Hollenhorst K.C. Huang Elizabeth Kidd is treating gynecologic cancer and per- children who are at greatest risk of learning difficulties. forming brachytherapy. Her research ISM

Shivaani Kummar Robbie Majzner Philip Pizzo Elsie Ross Birgitt Schuele Sharon Sha Katherine Travis 8 SEPTEMBER 9, 2019 INSIDE STANFORD MEDICINE