Unroofing relievessymptomsofheartanomaly I By Tracie White diothoracic surgery. MD, clinical assistant professor of car- study, andtheleadauthorisJack Boyd, medication alone. mias andfatigue,thatare nothelpedby symptoms, suchaschestpain,arrhyth- cardial bridgeswhohave incapacitating significant relief forpatientswithmyo- surgical unroofing issafeandprovides Surgery, finds that a procedure called online Oct. 13 in the myocardial bridges. A fifth, published has co-authored four research studies on ger, professor ofcardiovascular medicine, bridge?’” shesaid.Six years later, Schnitt- this patient could have a myocardial than resting on top of the organ. through the muscle of rather the heart runs condition in which a major artery bridge wasfound. The termdescribesa anomaly called a myocardialheart mill. During an autopsy, a little-known onatread attackwhilerunning - heart who hadsuddenlydropped deadofa physics professor atanotherinstitution back,” shesaid.She remembered ayoung tic tests. while examiningthesekindsofdiagnos- puter screen, onethatshe’d seenbefore on the com- curious motion of the heart complaining ofchestpain.She spotteda clinicatStanfordthe heart Health Care diogram of a young man who came to to buildnation’s center firsthadrontherapy Stanford Medicine, VA willcollaborate can be treated effectively. dose that can be delivered and thesize ofthe tumor that neighboring normaltissue. This toxicity limitsboththe cancer cells.But photonbeamscanalsoadversely affect therapy, inwhichbeamsofelectrons are usedtokill Volume 8, No.19Volume 8, other ionstokilltumor tissue. Hadron therapy usesbeamsofcharged particleslike protons, carbonionsand By KristaConger sat in her lab examining the echocar diologist attheSchoolofMedicine, n 2010, Ingela Schnittger, MD, a car Schnittger isseniorauthorofthe “I was thinking, ‘Wow, I wonder if “All ofthesuddenIhadthisflash- Many cancerpatientsare familiarwithradiation inside Stanford medicine Annals of ThoracicAnnals October 24, 2016 24, October Ka - - teryn nign, the study said. ago, butithaslongbeenconsidered be- ered during autopsies almost 300 years It’s acongenitalanomalythatwasdiscov- tomuchofthemedicalcommunity.tery a Ko Bridging continues to belittleunder- Myocardial bridgingremains amys- n /shutterst PublishedbytheOfficeofCommunication&PublicAffairs oc increase cancercure ratesbecauseitcantreat multiple tons, carbon,heliumandotherions—isexpectedto — whichrelies likepro - onbeamsofchargedparticles hadron therapy tocancerpatients.Hadron therapy laboration toestablishthenation’s firstcentertodeliver Palo AltoHealth Care System have announcedacol- k. co Now, Stanford Medicine andthe Veterans Affairs m Moonshot Committee’s report. tive. At theevent, thevicepresident shared the ident Joseph Biden’s CancerMoonshot initia - Oct. 17atthe White House of aspart Vice Pres- Killing tumorswithchargedparticles that both reduces harm and promotes healing.” identify optimalwaystooffertargetedtreatment center embodies this commitment, as we seek to School of Medicine. “Planning for the hadron individual,” saidLloyd Minor, MD,deanofthe to kill tumor tissue. ticles likeprotons, carbon ionsandother personalized healthcare thatistailored toeach ford Medicine iscommittedtoproviding more therapy, while also limiting adverse side effects. tumors orthoseresistant toconventional radio- Hadron therapyusesbeamsofcharged par- The collaborationwasannounced atanevent “Through ourprecision healthvision,Stan“Through - condition is what sent Schnittger along he said. and there isnoagreed-upon treatment,” said. stood andis oftenmisdiagnosed,Boyd That lackofunderstandingaboutthe “It’s nottaughtinmedicalschool, See hadron, page7 author. scholar Andrea Goldstein-Piekarski, PhD, isthe lead of Science. Williams istheseniorauthor. Postdoctoral line Oct. 10intheProceedings of theNational Academies havioral sciences. Leanne Williams, PhD, professorandbe- ofpsychiatry by confirmingitwithcross-validation techniques,” said strong becausewe demonstratedthataccuracyisrobust results are especially depression. tients recover from sants wouldhelppa- whether antidepres- 80 percent accuracy fully predicted with of Medicine success- searchers attheSchool as abuseorneglect,re- early life trauma, such of anysonal history combined withaper- By Tracie White antidepressants willhelp with highaccuracyif Researchers predict A paperdescribingthefindings waspublishedon- “We thinkour Using brainscans diagnosed at Stanford toenroll patientswithun- should it be treated? gerous? Did itcausesymptoms?How to know more: Couldbridgingbedan- her pathofinvestigation. She wanted In 2011, Schnittger designed a study See antidepress ts, page7 See pa Aks ulist unroofing, page6 a bir / shutterst Page 4 hospital. at the children’s encouragement kindness and has found Blue Foster patient, Misty years as a Over her a / shutterst oc oc k. k. co co m m Three individuals to receive medical school’s highest honor By Ruthann Richter notifying her that she would be recog- A distinguished physician-scientist, a lawyer with a nized with the school’s highest honor. long record of public service and a Silicon Valley entre- “Receiving this Dean’s Medal is preneur and philanthropist are this year’s recipients of such an unexpected and reward- the Dean’s Medal, the highest honor bestowed by the ing honor,” said Arvin, who began School of Medicine. her Stanford career as a postdoctoral The 2016 medal recipients are Ann Arvin, MD, the scholar in infectious diseases. “I’m so Lucile Salter Professor of Pediatrics and the university’s grateful for this and for all of the op- vice provost and dean of research; attorney John Levin, portunities I’ve had over these many chair of the Stanford Health Care board of directors; years at Stanford.” Ann Arvin John Levin Sean Parker and entrepreneur and philanthropist Sean Parker. From education to law The medal honors individuals who have made sci- that Stanford Medicine is doing and all the aspirational entific, medical, humanitarian, public service or other Levin was first drawn to Stanford by a program in notions that Stanford Medicine is moving toward.” contributions that have significantly advanced the mis- the School of Education that allowed him to complete Funding research in cancer immunotherapy sion of the school. The medals will be awarded today at a master’s degree in education while teaching at a lo- a ceremony. cal high school. He was then accepted to Stanford Law Parker is a philanthropist and entrepreneur with a re- “This year’s medal recipients have dedicated their School, where he received his law degree in 1973. He cord of launching genre-defining companies and orga- lives, skills and resources to helping solve some of our said he views both teaching and law as a service — a nizations. He is the founder and president of the Parker era’s hardest health problems,” said Lloyd Minor, MD, way to impact society and help others, as well as to cre- Foundation, which focuses on three areas: life sciences, dean of the School of Medicine. “They are also pio- ate opportunities and solve problems. He began a law global public health and civic engagement. Earlier this neers advancing our biomedical revolution in precision partnership in San Francisco, Folger Levin LLP, with year, the foundation announced a $250 million grant to health, making predictive, preventive and proactive care Stanford graduate Peter Folger 38 years ago. The firm launch the Parker Institute for Cancer Immunotherapy possible around the world.” focuses on transactions, dispute resolution and stra- to spur research on the relationship between the im- Focus on pediatric infectious disease tegic advice for businesses, individuals and nonprofit mune system and cancer. Stanford Medicine is one of organizations. the six participating institutions. Arvin has dedicated her career to focusing on infec- Levin has been involved in a wide array of commu- At 19, he co-founded the online file-sharing service tious diseases in children, particularly the varicella zoster nity activities and served on many boards, including a Napster, and at 21 he co-founded Plaxo, an online ad- virus, which causes chickenpox and shingles. Her clini- 10-year term as a Stanford University trustee. In addi- dress book. In 2004, he joined Mark Zuckerberg to cal studies, funded by the National Institutes of Health, tion to chairing the Stanford Health Care board, he is develop the online social network Facebook, and he helped contribute to the development of the chicken- a member of the board of directors of Lucile Packard served as Facebook’s founding president. In 2007, he pox vaccine and the shingles vaccine. She served as the Children’s Hospital Stanford and served as convening co-founded Causes on Facebook, which registered 180 chief of pediatric infectious diseases at Lucile Packard co-chair of the recently concluded Campaign for Stan- million people to donate money and take action around Children’s Hospital Stanford before being named a vice ford Medicine. social issues. provost in 2006. In that capacity, she oversees Stanford’s “The various ways in which I’m involved at Stanford “I’d like to thank Dean Minor and the entire team at interdisciplinary research institutes, university research are great sources of satisfaction to me,” he said. “I tre- Stanford Medicine for this extraordinary recognition,” policies and the Office of Technology Licensing. mendously appreciate and enjoy my many colleagues Parker said. “I’ve been fortunate to work closely with “As I think about my career and where I am now, I around the campus. I have the privilege of meeting and so many scientists and researchers at Stanford whose realize we have a new understanding and new tools to working with the most interesting people, who are fo- immunological research will undoubtedly lead to bet- probe the questions of human health and, in my case, cused on what I consider to be important problems in ter treatments for cancers and allergies. In my opinion, the questions of how viruses take over the human host thoughtful and serious ways. For me to be in a position they deserve all the recognition, and anything I can do and how it is that we have learned to live with them to be in those conversations and to have some small to draw attention to the incredible work that they’re through our immune responses and other mechanisms. impact in the direction of initiatives and decisions and doing — actually saving people’s lives and making this These present an endlessly fascinating set of questions,” programs is just a great joy and privilege. It’s something world a better place — is an incredible honor.” Arvin said. “There’s always the opportunity to do the I don’t feel I should be honored for. I feel quite the op- Parker was ranked No. 5 on the Chronicle of Philan- next experiment and to find out that you were right or posite. I feel quite sincerely that it’s of enormous benefit thropy’s 2014 Philanthropy 50 list. He has won a num- wrong in your hypothesis.” to my life.” ber of awards for his public service activities, including Arvin has won many awards, but she said she was lit- “The award is a happy bonus,” he added, “but I am the 2016 Roger Horchow Award for Outstanding Pub- erally speechless when she received the call from Minor really grateful to be engaged in all the remarkable things lic Service from the Jefferson Awards Foundation. ISM

Five faculty members elected to National Academy of Medicine

Four professors at the School of ceptors and ligands, particularly in the trieval, which Medicine and one at the School of Hu- fields of immunology, stem cell biology aims to make manities and Sciences have been elected and neurobiology. online bio- members of the National Academy of Krasnow is a professor of biochemis- medical data Medicine. try, executive director of the Wall Center sets more ac- Christopher Garcia, PhD; Mark Kras- for Pulmonary Vascular Disease and an cessible and now, MD, PhD; Mark Musen, MD, HHMI investigator. His research exam- reusable. PhD; Thomas Rando, MD, PhD; and ines the development of lung tissue and His research Laura Carstensen, PhD, now number the role of stem cells, the genetic origin focuses on among the academy’s 1,947 members of lung cancer and other lung diseases, intelligent Laura Carstensen Christopher Garcia Mark Krasnow and 146 international members. and the neural circuits that control systems, on- Garcia is a professor of molecular breathing and speech. tology engineering and biomedical and cellular biology and of structural Musen is a professor of medicine and decision support. He is a creator of biology, a Howard Hughes Medical In- of biomedical data science and director Protégé, an open-source framework stitute investigator and a member of of the Stanford Center for Biomedical for building intelligent systems. the National Academy of Sciences. His Informatics Research. He is principal Rando is a professor of neurology research focuses on understanding and investigator for the Stanford Center for and neurological sciences, director manipulating interactions between re- Expanded Data Annotation and Re- of the Glenn Center for the Biology of Aging and deputy director of the Inside Stanford Medicine is Stanford Center on Longevity. At

de the Veterans Affairs Palo Alto Health

i published monthly in July and Stanford Care System, he is chief of the neurol- December and semi-monthly Mark Musen Thomas Rando ns

i the rest of the year. ogy service and director of the Center medicine for Tissue Regeneration, Repair and is produced by Paul Costello Restoration. His research focuses on the ways that these changes influence cog- Office of Communication & Public Affairs Chief communications officer development of muscle tissue, the mo- nitive processing, decision making and Stanford University Susan Ipaktchian lecular control of muscle stem cell dif- health practices. School of Medicine Director of print & 3172 Porter Drive Web communications ferentiation, the functionality of older Established in 1970, the National Palo Alto, CA 94304 John Sanford muscle stem cells and the molecular ba- Academy of Medicine, formerly called Mail code 5471 Editor sis of muscular dystrophy and potential the Institute of Medicine, is recognized (650) 723-6911 Robin Weiss therapies for it. as a national resource for independent, http://med.stanford.edu/news/ Graphic designer Carstensen is a professor psychology, scientifically informed analysis and rec- the Fairleigh S. Dickinson Jr. Professor ommendations on health issues. The Send letters, comments and story ideas to John in Public Policy and founding director of academy’s almost 2,000 active members Sanford at 723-8309 or at [email protected]. the Stanford Center on Longevity. Her are selected on the basis of their profes- Please also contact him to receive an e-mail version of Inside Stanford Medicine. research addresses changes in motivation sional accomplishments and volunteer and emotion across adulthood and the service. ISM 2 October 24, 2016 Inside Stanford Medicine An inflammation test that may predict cardiovascular disease

By Bruce Goldman samples and measured these cells’ responses to stimula- The investigators blended 15 separate cytokine-re- tion by circulating signaling proteins called cytokines. sponsiveness measurements to generate a single number A blood test devised by School of Medicine scientists Many cytokines tend to shift the immune system into called a cytokine response score. This measure, which spits out a single number that strongly predicts the de- high gear. varied considerably among different older adults, was velopment of the world’s most prevalent medical disor- The investigators recorded the extent to which quite stable from year to year for any given individual. der: cardiovascular disease. several different types of immune cells mixed with A higher CRS is better, as it indicates a more-responsive While more research remains to be done, there’s cytokines in a lab dish increased the activation of intra- immune system and lower background inflammation. good reason to suspect that this test could be used to Timothy Archibald Intriguingly, individuals taking fish-oil supplements predict many other diseases of old age, said Mark Davis, had higher scores. (Fish oil is known to have anti-in- PhD, professor of microbiology and immunology. flammatory properties.) No other drug tested showed A paper describing the test was published online this correlation. Oct. 13 in Cell Systems. Davis is the senior author. Lead Cross-referencing cytokine response scores authorship is shared by former postdoctoral scholars Shai Shen-Orr, PhD, who is now an assistant profes- At the suggestion of study co-author Francois Had- sor at Technion-Israeli Institute of Technology in Haifa, dad, MD, a clinical associate professor of cardiovascu- and David Furman, PhD, now a consulting associate lar medicine, the cytokine response score of each of 40 professor at Stanford. older subjects was then cross-referenced against cardio- Mounting evidence suggests that many diseases that vascular-health assessments they underwent up to two become more common with advancing age do so be- years later. These assessments included a comprehensive cause the immune system begins to malfunction, said clinical history and tests of atherosclerotic plaque, arte- Davis, a Howard Hughes Medical Institute investigator rial stiffness and ventricular function. and the director of Stanford’s Institute for Immunity, Of the 40 subjects, 18 were in good cardiovascular Transplantation and Infection. health. Ten had already suffered cardiovascular events, In addition to responding more sluggishly to dan- and seven had sufficient atherosclerosis to be considered gers such as infectious pathogens or incipient tumors, subclinical. Five others had lesser signs of cardiovascular the aging immune system tends to spend its downtime problems and were considered borderline. — periods when it has no imminent challenge to re- The researchers found that cytokine response scores spond to — in a low-grade inflammatory state. Medical were inversely correlated with clinical signs of athero- experts are increasingly convinced that this constantly sclerosis and with two measures associated with the thrumming, systemic, inflammatory activity threatens heart’s ability to relax between beats. Importantly, the diverse tissues throughout the body. borderline subjects also had low cytokine response A better test? scores. The scores’ predictive value exceeded that of CRP tests, the current standard for measuring inflam- Cholesterol testing, a diagnostic mainstay, flags car- mation-based cardiovascular risk. diovascular risk only about half of the time, said Davis, For now, the test to obtain a cytokine response score who is also the Burt and Marion Avery Family Profes- is not available in clinics; it’s too complex and expen- sor. “For too many men experiencing a heart attack or sive. Davis said he and his colleagues want to try to sim- stroke, the first observed hint of cardiovascular risk is plify it and drive down the cost. their death,” he said. “The CRS may be a useful proxy for healthy aging,” Testing for levels of CRP, a circulating protein linked said Davis. “And its predictive accuracy in cardiovascu- to inflammation, has been shown to further enhance lar disease further substantiates the inflammatory un- the prediction of cardiovascular risk, even among pa- derpinnings of that prevalent, age-related condition.” tients with normal cholesterol levels. A CRP reading is The team’s work is an example of Stanford Medi- A blood test developed by Mark Davis and his colleagues may be relatively simple to get, requiring only a blood draw and able to predict the development of cardiovascular disease. cine’s focus on precision health, the goal of which is to relatively straightforward lab tests. anticipate and prevent disease in the healthy and pre- The new test developed by the Stanford researchers is cisely diagnose and treat disease in the ill. more complicated but appears to have superior diagnos- Other Stanford co-authors of the study are former tic value to either the cholesterol or CRP test. Rather cellular substances called STAT proteins. In response to research assistant Brian Kidd, PhD, now at the Icahn than testing circulating inflammatory proteins, it tests this stimulation, STAT proteins are known to undergo School of Medicine at Mount Sinai in New York City; for the response of immune cells themselves to inflam- small chemical changes, causing them to head into a research and development engineer Patricia Lovelace; mation — a signal that appears to be more stable and cell’s nucleus and turn on batteries of genes that stir the research assistant Yin-Wen Huang; Yael Rosenberg-Has- hence a more robust diagnostic. In the study, it was able erstwhile quiescent cell into a frenzy of immunological son, PhD, immunoassay and technical director at the to detect early cardiovascular irregularities in otherwise activity. Institute for Immunity, Transplantation and Infection; asymptomatic individuals. When immune cells from young people were stimu- Sally Mackey, associate director of the Stanford-LPCH The researchers took advantage of data from the first lated with certain cytokines, the activation levels of Vaccine Program; Armaghan Grisar, MD, research fel- three years of what was to become a nine-year longitu- STAT proteins skyrocketed. When the same thing was low at the Stanford Cardiovascular Institute; associate dinal project carried out at Stanford under the direction done to immune cells from old people, STAT-protein professor of microbiology and immunology Holden of study co-author Cornelia Dekker, MD, a professor activity rose a lot less. Maecker, PhD; professor of microbiology and immu- of pediatric infectious disease. In all, 90 adults, divided However, pre-stimulation levels of STAT-protein nology Yueh-hsiu Chien, PhD; professor of radiology into two groups — people younger than 40 and people activation in immune cells from old people were sub- Joseph Wu, MD, PhD; and former associate professor older than 60 — were assessed annually at high resolu- stantially higher than in those from young people, of pediatrics Atul Butte, MD, PhD, now at the Univer- tion with a battery of tests as to the state of their im- suggesting that older people’s immune systems are con- sity of California-San Francisco. mune system, how it varied from year to year within stantly somewhat revved up when they should be at The study was funded by the National Institute of and between individuals and how this related to clinical rest. Allergy and Infectious Diseases, the Ellison Medical markers of inflammation. Still, older people’s pre-stimulation STAT-protein ac- Foundation, the Howard Hughes Medical Institute, the Isolating immune cells tivation levels, and these proteins’ activation in response Israeli Science Foundation, the Stanford Cardiovascular to cytokine stimulation, varied widely between individ- Institute and the Stanford Center on Longevity. For the Cell Systems study, the researchers isolated uals. Some showed few signs of it, while in others it was Stanford’s Department of Microbiology and Immu- several types of immune cells from individual blood pronounced. nology also supported the work. ISM

Two researchers receive funding from BRAIN Initiative P l e as e Two School of Medicine research- ing at 60 institutions. These awards ex- namics in health and disease.” He and give blood ers are among the recipients of the third pand NIH’s efforts to develop new tools his colleagues plan to develop novel algo- Blood type needed: round of grants from the National Insti- and technologies to understand neural rithms for identifying dynamic functional O-, B- and AB- tutes of Health’s BRAIN Initiative. circuit function and capture a dynamic networks in the brain and characterizing More than 100 new awards, totaling view of the brain in action. The initiative network interactions between brain re- To request an appointment, call 723-7831 more than $70 million, are being given was launched in 2014. gions involved in cognitive tasks. or you can make an appointment online. this year to over 170 investigators work- The two Stanford recipients are Vinod Butts Pauly received $393,000 from Menon, PhD, professor of psychia- the NIH’s National Institute of Mental 3373 Hillview Ave., Palo Alto try and behavioral sciences, and Health for a project titled “MR-guided 445 Burgess Drive, Menlo Park, Kim Butts Pauly, PhD, professor of focused ultrasound neuromodulation 515 South Dr., Mountain View radiology. of deep brain structures.” Through the Menon received $387,000 work, she hopes to develop noninvasive http://bloodcenter.stanford.edu from the NIH’s National Insti- technology that combines focused ultra- tute of Biomedical Imaging and sound neuromodulation for therapeutic Bioengineering for a project titled purposes with magnetic resonance im- “Novel Bayesian linear dynami- aging to accurately predict ultrasound cal systems-based methods for dis- intensities and temperatures at the target Kim Butts Pauly Vinod Menon covering human brain circuit dy- site and throughout the brain. ISM Inside Stanford Medicine October 24, 2016 3 Study: Withholding amino acid depletes blood stem cells By Christopher Vaughan ford’s Ludwig Center for Cancer Stem Cell Research open up a new research field of stem cell metabolism A dietary approach to depleting blood stem cells and Medicine, has a particular interest in one kind of and become the basis for a whole range of dietary thera- may make it possible to conduct bone marrow trans- stem cell that may be affected by valine deficiency. If pies,” he said. plantations without the use of chemotherapy or radia- leukemia stem cells are also vulnerable to valine defi- “It also reinforces the importance of a well-rounded tion therapy, according to researchers at the School of ciency, Nakauchi said, it may open the door to a dietary diet to keep all our cells healthy,” he added. Medicine. therapy for these blood cancers. As with bone marrow The other Stanford co-author is postdoctoral scholar The discovery, made in collaboration with research- transplantation, a dietary treatment for cancer would Adam Wilkinson, PhD. ers at the University of Tokyo, may also become a new probably be much less toxic than chemotherapies now This work was supported by the California Insti- way to treat certain cancers without chemo or radiation, being used, he said. tute for Regenerative Medicine, the Siebel Foundation, which can cause severe side effects. The lightbulb Ludwig Cancer Research, the Japan Science and Tech- The researchers showed that a diet deficient in the nology Agency, the Japanese Ministry of Education, essential amino acid valine could effectively deplete The new study came about after Yamazaki was re- Culture, Sport, Science and Technology, and the Japan the population of blood stem cells in mice and allow viewing the scientific literature and found an article in Society for the Promotion of Science. them to be successfully transplanted with blood stem a 1946 issue of Science. It was co-authored by the late Stanford’s Department of Genetics and the Stanford cells from other mice. The researchers also showed that Stanford researcher Arthur Kornberg, who would go on Institute for Stem Cell Biology and Regenerative Medi- human blood stem cells in the laboratory were affected to receive the 1959 Nobel Prize in Physiology or Medi- cine also supported the work. ISM by a lack of access to valine, sug- cine. In his 1946 research, Korn- wing hon films gesting that the same therapeutic berg and his colleagues showed approach may work in humans. “This work could open up that certain types of anemia in rats A paper describing the find- could be treated by giving them ings was published online Oct. a new research field of mixtures of purified amino acids. 20 in Science. The lead author stem cell metabolism.” Yamazaki, Nakauchi and their is Yuki Taya, a former graduate colleagues were intrigued and did student at the University of To- the experiments that Kornberg did kyo. The senior authors are Hiromitsu Nakauchi, MD, not do: testing the effects of the presence or absence of PhD, a professor of genetics at Stanford, and Satoshi specific amino acids on blood stem cells. The research- Yamazaki, PhD, an associate professor at the Center for ers found that in a lab dish, a lack of valine or another Stem Cell Biology and Regenerative Medicine at the amino acid, cysteine, would make the growth of mouse University of Tokyo. blood stem cells impossible. Effects of valine-deficient diet Then, the researchers asked a company to create mouse food that was deficient in only these specific “Bone marrow transplantation is a toxic therapy,” amino acids, and fed the mice this diet for four weeks. said Nakauchi, who is also a member of Stanford’s Insti- They found that the valine-deficient diet, but not the tute for Stem Cell Biology and Regenerative Medicine. cysteine-deficient diet, depleted blood stem cells in the “We have to do it to treat diseases that would otherwise mice. “Unlike valine, cysteine is not an essential amino be fatal, but the quality of life afterward is often not acid, which means that the body can make some of it good.” itself,” Nakauchi said. “All of our valine has to come He added, “Relative to chemotherapy or radia- from our diet, however.” tion, the toxicity of a diet deficient in valine seems to The current dietary method complements other be much, much lower. Mice that have been irradiated work recently reported by Stanford scientists for using look terrible. They can’t have babies and live for less antibodies instead of chemotherapy or radiotherapy to than a year. But mice given a diet deficient in valine clear out blood stem cells in preparation for bone mar- can have babies and will live a normal life span after row transplantation. “The two methods might even be transplantation.” used together to provide an even more effective, gentler The effect of a valine-deficient diet is fairly specific therapy,” Nakauchi said. to blood stem cells, but there seem to be other sorts The mechanism by which amino acid deficiency af- of stem cells that may also be affected, Nakauchi said, fects blood stem cells is unknown, he said, but that will including hair stem cells and some T cells. Other types be the focus of future research. Now that this amino of stem cells may also be affected, but the effects are acid has shown promise as the basis for a dietary ther- not nearly as widespread or extreme as those caused by apy, Nakauchi thinks scientists may find other specific A 1946 paper by the late Arthur Kornberg led Hiro Nakauchi and his chemotherapy or radiation therapy, he said. kinds of stem cells that are affected by the presence or colleagues to discover that removing valine, an essential amino acid, Nakauchi, who is also an investigator at Stan- absence of particular amino acids. “This work could from the diet of mice depleted their blood stem cells.

Common prostate cancer treatment linked to later dementia

By Jennie Dusheck from ordinary patient medical records. gens in prostate cancer pa- the prior dementia history The paper describing the research was tients since the 1940s. In the of the patient, we may want A new retrospective study of patient published online Oct. 13 in JAMA On- United States, about a half- to consider alternative treat- medical records suggests that men with cology. Kevin Nead, MD, DPhil, a resi- million men currently receive ment, particularly in light prostate cancer who are treated with dent at the University of Pennsylvania ADT as a treatment for pros- of a recent prospective study testosterone-lowering drugs are twice as who got his medical degree at Stanford, tate cancer. from the U.K.,” said Shah. likely to develop dementia within five is the lead author. Nigam Shah, MBBS, ‘The risk is real’ That study, published in Sep- years as prostate cancer patients whose PhD, associate professor of biomedical tember in The New England testosterone levels are not tampered with. informatics research at Stanford, is the A 2015 study by the same Journal of Medicine, revealed The study, by researchers at the Stan- senior author. authors found an associa- Nigam Shah that prostate cancer patients ford School of Medicine and the Univer- Testosterone can promote the growth tion between ADT and Al- randomized to either active sity of Pennsylvania Perelman School of of prostate tumors, and so clinicians zheimer’s disease. In the new paper, the monitoring, surgery or radiation therapy Medicine, also demonstrates emerging have used androgen deprivation therapy team expanded their work to include all had the same risk of death from the techniques for extracting biomedical data to lower testosterone and other andro- several other forms of dementia. “When cancer after 10 years. Ninety-nine per- Alexander Raths / Shutterstock.com we published our last paper, a letter to cent of men in the study survived regard- the editor pointed out that Alzheimer’s less of initial treatment. These startling is often confused with vascular demen- results suggest that active monitoring of tia,” said Shah. “So instead of looking for prostate cancer patients may be as good Alzheimer’s and dementia separately, we as early radical treatment and may cause decided to aggregate them into a higher- fewer side effects. level category — all dementias and cog- And because the actual number of pa- nitive decline.” Such aggregation could tients possibly at risk for dementia from minimize the question of misdiagnosis, androgen deprivation therapy is small, it Shah said, and increase the sample size to makes sense when weighing the value of provide more statistical power. prescribing ADT to try to identify which The team looked at deidentified re- prostate cancer patients might be vulner- cords from Stanford Medicine’s clini- able to dementia, said Shah. cal-research data warehouse for nearly The new study adds to a growing 10,000 patients with prostate cancer. Of body of evidence supporting Stanford the 1,829 who received androgen depri- Medicine’s precision health approach, vation therapy, 7.9 percent developed de- the goal of which is to anticipate and mentia within five years, compared with prevent disease in the healthy and pre- 3.5 percent of those not treated with cisely diagnose and treat disease in the ill. ADT. Nead and Shah cautioned that pros- “The risk is real and, depending on See Prostate, page 5 4 October 24, 2016 Inside Stanford Medicine Growing up in a hospital: My 25 years with Packard Children’s

By Misty Blue Foster and hips. For my frequent in- courtesy of misty blue foster like the rest of the applicants can. For most people, the trajectory is clear: When patient stays, my foster mom She just may have to go to the you are a kid and you’re sick, you go to the pediatri- would check me in to the bathroom more often than some cian. If you have a chronic medical condition, as in hospital and then leave. I’d of your other students,” Kennedy my case, you establish a team of pediatric specialists hear other families talking and told the schools. who can provide for your health issues on a consis- laughing and soothing their It paid off. Today I am a li- tent basis throughout your childhood. As you get children in the neighboring censed vocational nurse at the older, you work with these specialists to transition rooms as I sat alone, with only Veterans Affairs Palo Alto Health your care to a new team of doctors who are better the sounds of the beeping Care System where I work in the suited for treating adults. and whirling of the machines medical specialty clinics, caring For me, however, this hasn’t been the path. I am for company. This experience for patients in the cardiology, 30 years old, and I am still an active patient at Lu- taught me to advocate for my- urology and neurology units. I cile Packard Children’s Hospital Stanford. My con- self and to ask questions so I also work in Blind Rehabilita- ditions are so complex that they require the care of could be part of the decisions tion Services with veterans who specialists who have been with me since early child- for my own care. have lost their vision due to dis- hood. Beyond my medical care, these specialists Growing up at Packard ease or blast injuries, and I am have been committed to me in a bigger way: They Children’s pursuing my master’s degree in courtesy of misty blue foster public health at San Jose State My nurses and doctors University. were impressed by my precoc- I’ve paved the way for my- ity and concerned about my self, and I hope that through my lack of parental support, so work as a nurse I will be able to they went above and beyond Foster with William Kennedy, a Stanford urolo- pay forward the extraordinary and gave me what felt like a gist who cared for her. care I’ve experienced throughout family. They were some of the my life. I’ve always said, “You first adults in the world who respected my voice and can’t always control what you are given in life, but made me feel safe, welcome and deserving of a good you can control what you do with it.” I’m striving chance in life. for that every day. ISM One nursing assistant in particular, Petie Cote, now retired, would visit with me for hours after her Misty Blue Foster is a licensed vocational nurse at the shifts ended. She would bring me my favorite snacks Veterans Affairs Palo Alto Health Care System. and take me on walks around the hospital. Today, Petie remains a huge part of my life. She and her late courtesy of misty blue foster husband gave me away at my wedding in 2006, and I even call her “Mom.” Foster at age 6 during a stay at Packard Children’s. I also have Packard “grandparents.” I met Grandpa Dave Olsen when, as a volunteer, he came have become my family, which is something I truly to read stories to me, something he dedicated him- did not have until I found myself in the hospital. self to after losing his own grandson to cancer. I ex- Finding my voice plained to him that I was alone, and he assured me, “I’ll be your grandpa.” He kept true to his promise, Born 3 months premature to a heroin-addicted and in the years that followed we stayed close, shar- mother, I was diagnosed with spina bifida and cloa- ing holidays and life’s milestones. cal exstrophy, a rare birth defect of the abdominal Pursuing my dreams wall in which the organs are outside of the body. These conditions come with a host of related medi- As I got older, I expected to phase out of the cal complexities, which led to frequent, unplanned children’s hospital. When I was in my 20s and mar- hospitalizations throughout my childhood. ried, I started to see adult specialists. But I always My mom spent much of my early years in and came back to Dr. William Kennedy [a professor of out of prison, where she passed away when I was urology] and his team at Packard Children’s. They just 5 years old due to health issues from her years knew my story and my medical history, and they of drug abuse. After her death, I was permanently were able to treat my congenital complexities, which placed in foster care, and this was the beginning of a adult specialists have struggled to navigate. Also, I’ve long, painful chapter of my life. I spent 14 difficult always felt this was a place where my voice was re- years in the system. During this time, I was deprived spected, no matter how big my dreams became as I of the medical care that I needed at home, and I thought about my future outside the hospital walls. was exposed to gangs, homelessness, drugs, alcohol Thanks to the care and encouragement I received and neglect, including extremely unsanitary living at Packard Children’s, I was inspired to pursue my conditions. dream of becoming a nurse. When administra- As a result, I developed frequent infections that tors reviewed my nursing school application and often required hospitalization. Over the years, I doubted whether I was physically capable of such a have had more surgeries than I can count to main- demanding job, my doctors convinced them other- Foster with Petie Cote, a retired nursing assistant at Packard tain function in my bowels, bladder, spine, pelvis wise. “She can walk, talk, think and do everything Children’s, after Foster’s Skyline College graduation ceremony.

Prostate The new retrospective study of pa- record studies offer powerful ways to testing associations they knew were not continued from page 4 tient records took only a few weeks, said identify hypotheses about efficacy and true, calibrating their approach. Shah. “We are working to make such safety that are worth further testing in Retrospective studies of patient medi- tate cancer patients who are receiving studies as simple as a Google search,” he clinical trials, said Mahaffey, who is vice cal records aren’t meant to replace ran- ADT shouldn’t make changes to their said. “We were down chair of clinical domized clinical trials, said Shah. “If we medications without talking to their to weeks in this one, “I was surprised at research in Stan- had infinite funding, we’d do a trial for physicians. and our current ef- ford’s Department everything. But we don’t have that,” he Cheaper and faster forts, which are how ubiquitous the of Medicine. said. “These cheap, few-week studies can funded by the Dean’s effects on all types of But the lack guide us where to point our clinical trial “I was surprised at how ubiquitous Office, have gotten of randomization dollars.” the effects on all types of dementia were, us to close to two to dementia were.” in health record Other Stanford-affiliated co-authors but I would definitely not alter clinical three days.” studies means the are medical student Greg Gaskin; senior care based on our results,” Nead said. In contrast, a prospective, random- results can be misleading, cautioned scientist Cariad Chester; and associate He added that he would like to see a ized clinical trial to study the same Mahaffey. “This work is important,” he professor of vascular surgery and of car- prospective, randomized clinical trial question would probably require thou- said, “but there are a number of exam- diovascular medicine Nicholas Leeper, to establish whether ADT can be more sands of patients, years to complete and ples of such retrospective studies where MD. firmly linked to an increased risk of de- many millions of dollars, said Kenneth the results have been completely wrong.” This research was supported by the mentia and to help identify what kinds Mahaffey, MD, a Stanford professor of Shah said the approach his team used National Library of Medicine and the of patients might be vulnerable to that medicine who was not involved in the minimized the chance of being wrong. National Institute of General Medi- increased risk. He anticipates that check- study. For example, the authors matched pa- cal Sciences. Stanford’s Department of ing for dementia risk in people treated Studies of existing patient health re- tients who received ADT and those who Medicine also supported the work. with ADT will be part of future ran- cords are far cheaper and faster than did not according to how sick they were. Shah has three pending patents on domized, clinical trials that have a larger “gold standard” randomized, clinical They also explicitly and empirically effective ways to mine electronic health focus. prospective studies. And patient health quantified the chance of being wrong by records data. ISM Inside Stanford Medicine October 24, 2016 5 ious.’ They get belittled, not taken seriously, and they sleep deprivation — anything that drives up the heart Unroofing get really depressed.” rate would also cause ischemia.” continued from page 1 Unroofing Prior to surgery, study participants filled out the Se- attle angina questionnaire, a three-page survey describ- chest pain and examine them in the catheterization Unroofing the myocardial bridge entails cutting ing their symptoms and ranking their quality of life. laboratory using diagnostic-imaging techniques, such through the heart muscle to uncover the tunneled ar- Then six months after the surgery, they filled out the as angiograms, to visualize the arteries of the heart and tery, thus relieving compression on the artery caused by survey again. its chambers. the bridging. This is a comprehensive survey often used in cardiac “Sometimes we saw myocardial bridging on the an- The surgery is known to be effective, Boyd said. research to ask how much pain the patient has, how fre- giogram,” she said. “Then we’d use an intravascular ul- However, concerns that healthy heart mus- quently they have it, how much it limits trasound to see them more clearly.” cle could be damaged during the operation their life. Since then, 150 participants in this ongoing study have slowed its adoption. “At Stanford, we Results showed that the average rank- have been diagnosed with myocardial bridges. Research use new imaging techniques to map the ing of quality of life prior to surgery by has involved measuring blood flow and blood pressure bridge muscle very precisely, and we per- the patients was 25 percent. After surgery, in the bridging vessel. Schnittger and her colleagues form the unroofing with conservative surgi- that figure jumped to 78 percent. were able to show that compression of the heart muscle cal techniques to safeguard the healthy heart “Our patients come back after surgery can reduce or cut off blood flow in the artery, result- muscle,” he said. so grateful,” Schnittger said. “They have ing in serious problems, including angina, myocardial In the past, the surgery was done only as suffered for so long — finally they’ve ischemia, acute coronary syndrome, left ventricular a treatment of last resort, Schnittger said. found doctors who understand them. dysfunction and malignant ventricular arrhythmias. “You took a patient very, very occasionally Ingela Schnittger “One patient, a mother of five, was so For some, symptoms are severe to surgery when everybody had tossed their symptomatic before surgery she had ar- hands up,” she said. “Stanford probably did ranged her whole life around her symp- “It hadn’t before been proven with blood-flow stud- no more than one surgery a decade in the past.” toms. She didn’t play with her children outside; she ies that circulation got impaired enough to cause isch- But with Schnittger and her team, including study couldn’t even pick them up at the playground. She was emia, inadequate blood flow and oxygen to the heart co-author Jennifer Tremmel, MD, assistant professor of basically housebound. She couldn’t do laundry or go muscle,” Schnittger said. cardiovascular medicine, and Ian Rogers, MD, clinical grocery shopping. After surgery, she could do all those Most patients with the condition remain asymp- assistant professor of cardiovascular medicine and of things — laundry, play outside with her children, go tomatic. Some have minor symptoms that can be pediatric cardiology, helping to guide the surgeries, the for a walk. It’s a life-changer. controlled with medication, such as beta blockers number performed at Stanford Medicine has increased “Our team wants to spread the word, to educate the and calcium-channel blockers. substantially. More than 80 have medical community that this is a real thing,” she added, But a small portion have se- been performed at SHC and Lucile noting that a myocardial bridge clinic has been estab- vere symptoms that greatly af- “Many of these patients Packard Children’s Hospital Stan- lished at Stanford Health Care. fect their daily lives. Some are have these heartbreaking ford in the past five years. The work is an example of Stanford Medicine’s focus left homebound. Many make For the new study, the research- on precision health, the goal of which is to anticipate repeated trips to emergency stories to tell.” ers examined 50 adult patients who and prevent disease in the healthy and precisely diag- rooms complaining of heart- between 2011-15 underwent the nose and treat disease in the ill. attacklike symptoms, only to get sent home with no unroofing procedure because of severe symptoms that Other Stanford co-authors are postdoctoral scholar answers. medication had failed to manage. The first 35 were Vedant Pargaonkar, MD; resident David Scoville, MD; “Many of these patients have these heartbreaking performed using a heart-lung machine for life support. Takumi Kimura, MD, PhD, Shigemitsu Tanaka, MD, stories to tell,” Schnittger said. “They can’t hold a job, The last 15 were performed off-pump on a beating PhD, and Ryotaro Yamada, MD, PhD, all members of they can’t travel, they can’t take care of their families. heart. the Stanford University Cardiovascular Core Analysis Most cardiologists are completely at a loss. They know Studying the condition in the lab Laboratory; Michael Fischbein, MD, PhD, associ- myocardial bridges exist, but they have been taught ate professor of cardiothoracic surgery; and R. Scott they are benign and never cause problems. “We studied the patients’ hearts comprehensively in Mitchell, MD, professor emeritus of cardiothoracic “When these patients go to the ER, and they go the lab, proving there was ischemia when we simulated surgery. there a lot, all the cardiology tests come back normal. a stress test by infusing drugs that increased the heart Stanford’s departments of Medicine and of Cardio- They’re told, ‘Here’s a little Valium. I think you’re anx- rate,” Schnittger said. “Increased heart rate, anxiety, thoracic Surgery supported the work. ISM

o b it ua ry Radiologist, pianist F. Graham Sommer dies at 70

By Jennie Dusheck Academy of Radiology Research’s Dis- bachelor’s degree in physics from the support composers under age 35 and tinguished Investigator Award. His ge- University of Victoria and a medi- to promote the creation of new musi- Frank Graham Sommer, MD, a nial personality helped create a warm, cal degree from McGill University in cal works, will launch in 2017 professor emeritus of radiology at the collegial and professional environment Montreal. He joined the faculty at Besides his work and his music, School of Medicine and an accom- in the medical school’s Department Stanford in 1979. Sommer enjoyed biking, skiing and plished pianist, died Oct. 2 of amyo- of Radiology, said colleague Michael A ‘Renaissance radiologist’ windsurfing, as well as playing tennis, trophic lateral sclerosis at his home on Federle, MD, a professor of radiology. golf, racquetball and squash. the Stanford campus. He was 70. “He always lived life to the fullest,” Sommer had wide-ranging interests Federle called him a “tremendous An expert in ultrasound imaging said Federle. in his field, humorously characterizing athlete.” In a typical experience play- and other radiological imaging tech- Sommer was born in Victoria, Brit- himself as a “Renaissance radiologist.” ing golf with Sommer, said Federle, niques, Sommer received the 2016 ish Columbia, in 1946. He earned a He studied and promoted improved Sommer would show up to tee off, imaging techniques and is known for having already taken a 20- or 30-mile courtesy of McGill University his work on ultrasound and imaging mountain bike ride. “Then he’d walk blood flow in the kidneys. 18 holes of golf.” “He was a driven man,” said his Leclair said Sommer planned ev- wife, Denise Leclair. “He had such a erything he did carefully, carrying his hungry mind; it drove him.” research habits into his daily life. In But he didn’t conform to the ste- 1995, when Sommer and Leclair had reotype of the super-focused, socially just met, she recalled: “We were mak- inept scientist, she said. Sommer was ing a recipe of salmon in filo dough.” adventurous, thoughtful, kind, gener- It was his habit to make a recipe many ous and charming, she said. He was times, slightly altering the recipe each also very logical and a careful plan- time until he thought it was perfect, ner, she said. “But then he would say she said. But Leclair impulsively de- something, and it would just stop the cided to throw some blackberries in- conversation and make you laugh.” side the filo dough with the salmon. When not at work, he would often “He was astounded!” Leclair laughed. play the piano for audiences at Filoli, And he never forgot that she had done an estate in Woodside that’s open to that, often bringing it up in later years. the public, and at restaurants and se- In addition to Leclair, Sommer is nior centers — favoring classical, pop- survived by a sister, Anne Axford, of ular and ragtime music. West Vancouver, British Columbia. A Sommer recently pledged $1 mil- celebration of his life will be held at lion to McGill University to fund a 1 p.m. Oct. 28 at Alta Mesa Funeral An expert in ultrasound imaging and other radiological imaging techniques, F. Graham Sommer Canada-wide competition for com- Home, 695 Arastradero Road, Palo was also an accomplished pianist and would perform at restaurants and senior centers. posers. The competition, intended to Alto. ISM

6 October 24, 2016 Inside Stanford Medicine Leslie Williamson a person’s life, the researchers said. “For Antidepressants those whose amygdala is affected by early continued from page 1 life stressors, they have different ways of responding to treatments and perceiving MRI scans and questionnaire the world,” Goldstein-Piekarski said. “Currently, finding the right antide- For example, a child experiencing pressant treatment is a trial-and-error abuse by a caregiver learns to be hy- process because we don’t have precise pervigilant and very aware of both the tests,” Williams said. “For some people negative and positive emotions coming this process can take years. As a result, from that person in order to avoid fu- depression is now the leading cause of ture adverse events, Goldstein-Piekarski disability.” said. As a result, the amygdala becomes For the trial, the researchers con- hypersensitive to these emotions. And ducted brain scans on 80 participants that’s useful at that time. with depression. Participants lay in a “Unfortunately, sometimes the amyg- functional MRI machine while viewing dala maintains this hypersensitive trajec- images of happy faces and fearful faces tory in later life, but it changes slightly,” on a screen in front of them. Each face Andrea said. “As an adult, they lose out triggered brain circuits involving the on that ability to respond to the more amygdala, an almond-shaped structure positive emotions.” linked to the experiencing of emotions. By using functional MRI to examine The scans were conducted both be- the “emotional brain” — the network fore and after an eight-week treatment or circuit of the brain that responds to period with three commonly used an- emotions — the researchers quantify tidepressants: sertraline (Zoloft), es- how early childhood trauma affected the citalopram (Lexapro) and venlafaxine brain. (Effexor). Participants also completed Those participants whose emotional a 19-item questionnaire on early life brain retained the capacity to respond stress, which assessed exposure to abuse, well to positive emotions — the happy neglect, family conflict, illness or death faces in the fMRI test — had good (or both), and natural disasters prior to chance of recovering with antidepres- the age of 18. sants, the researchers said. The researchers analyzed the pretreat- “For those patients who have lost this ment imaging and the questionnaire capacity, putting them down an anti- to predict how the individual patients depressant path is likely to cause more would respond immediately after the heartache,” Williams said. “That’s when eighth week. “Our predictions were cor- you would consider other types of treat- rect,” Goldstein-Piekarski said. ment. First, treat the effects of the child- Using a statistical analysis called pre- hood trauma through methods such as dictive modeling, study results showed trauma-informed psychotherapy, and that participants exposed to a high level then consider antidepressants.” Leanne Williams and her colleagues say that using functional MRI scans and a questionnaire can help of childhood trauma were most likely to Recommendation: Order brain scan predict which patients are likely to be helped by antidepressants. recover with antidepressants if the amyg- dala was reactive to the happy faces. The researchers say results from this Those with a high level of childhood study could be useful for physicians who depressant treatment is recommended patient’s suffering continues while the trauma whose amygdala showed low usually provide the first line of treatment depending on the varying levels of child- disease progresses. reactivity to the happy faces were less for patients with depression. They envi- hood trauma and brain-scan results from The work is an example of Stanford likely to recover with antidepressants. sion the integrated clinic of the future in patients. Medicine’s focus on precision health, the “We were able to show how we can which physicians ask about childhood “We interacted with a lot of pri- goal of which is to anticipate and pre- use an understanding of the whole per- trauma and order a five-minute brain mary care providers during this study vent disease in the healthy and precisely son — their expe- scan to help deter- — about 200 of them,” Williams said. diagnose and treat disease in the ill. riences and their mine the best line “The practitioners themselves like the Other Stanford co-authors of the brain function and “We can now predict who of treatment. idea of a scan. They want to know who study are postdoctoral scholar Erin the interaction is likely to recover on “If we are is likely to benefit from antidepressants, Green, PhD; Trisha Suppes, MD, PhD, between the two thinking about and when they should refer for specialist professor of psychiatry and behavioral — to help tailor antidepressants in a way trying to get this psychiatric services including psycho- sciences; Alan Schatzberg, MD, profes- treatment choices,” that takes into account right the first time, therapy. Currently, there is nothing to sor of psychiatry and behavioral sciences; Williams said. “We it’s useful to con- help them make that decision.” and Trevor Hastie, PhD, professor of can now predict their life history.” sider the option of Today, if the first line of treatment statistics. who is likely to re- ordering a scan,” doesn’t work, patients spend an aver- The study was funded by Brain Re- cover on antidepressants in a way that Williams said. “It’s already done for so age of two to three years going through source Pty. Ltd. and by grants from the takes into account their life history.” many other things — a broken leg, a a trial-and-error period before getting National Institute of Mental Health. Effects of childhood trauma heart problem, a potential tumor.” treatment that helps, Williams said. She Williams has received consulting fees The study also provides a table that added that by that time, the disabil- from Brain Resource Pty. Ltd. Childhood trauma can change both the researchers say could ultimately be ity burden has increased tremendously, Stanford’s Department of Psychiatry the structure and function of the amyg- used by practicing physicians to de- with lost productivity of up to $14,000 and Behavioral Sciences also supported dala in ways that can affect the rest of termine the threshold at which anti- a year per employee, not to mention the the work. ISM

Stanford Medicine and explore ways to continue taking cancer. Hadron veterans’ health care into the 21st century. The state-of- “Lucile Packard Children’s Hospital and Stanford continued from page 1 the-art hadron center would not only improve the lives Medicine have long been at the vanguard of pediat- of those affected by cancer, but further demonstrate ric care and scientific discovery to improve the lives of Unlike photons or electrons, which release energy along VA’s ability to partner on pioneering innovation and children,” said Christopher Dawes, president and CEO the length of their path, the charged particles deliver exceptional health care.” of Lucile Packard Children’s Hospital Stanford and most of their damaging energy in one burst inside the Goal of improving survival rates Stanford Children’s Health. “Planning for the hadron tumor. They are more effective at damaging DNA in- center, which provides proton and heavier charged par- side of cancer cells, and some studies have suggested The technology could bring hope to patients suffer- ticle therapy, is no exception. It will change the way we they can effectively incite an immune response against ing from currently incurable tumors. fight cancer and reduce late toxicity in pediatric and the tumor. Charged particle beams can also be shaped “Currently it is not possible to effectively treat young adult patients.” to treat tumors of various sizes and shapes. large-volume tumors or metastatic disease with con- The center also will be used to conduct research and There are about 10 carbon-based hadron therapy ventional radiotherapy due to concerns about toxicity,” clinical trials to validate the potential of hadron therapy centers in the world, but none in the United States. said Quynh Le, MD, professor and chair of radiation in cancer patients and to miniaturize the technology The center is expected to be located on the grounds oncology at the School of Medicine and the Katharine (in collaboration with the SLAC National Accelerator of the VA-Palo Alto. If all goes well, the collaborators Dexter McCormick & Stanley McCormick Memorial Laboratory) to make it more affordable and accessible hope to begin treating cancer patients in about four Professor. “I believe particle beam therapy will trans- for cancer patients around the world. years. form the care of cancer in this country. We will have “We at Stanford Medicine have been working on “Hadron therapy represents a new way forward in the potential to cure patients with radio-resistant tu- this for several years and are thrilled that we will have cancer care,” said David Entwistle, president and CEO mors. In addition, we hope to also use this approach to the opportunity to work with the Palo Alto VA to bring of Stanford Health Care. “Stanford Medicine is hon- boost the survival and decrease the toxicity experienced the nation’s first hadron therapy system to Stanford,” ored to collaborate with the VAPAHCS to bring this by patients with large-volume metastatic disease. Our said Sridhar Seshadri, vice president for cancer services therapy to our patients, giving them unprecedented ac- goal is to improve the survival of patients who are cur- at Stanford Health Care. “We believe that Stanford cess to the latest cancer science and treatment.” rently considered incurable.” Medicine has the innovative spirit and the expertise to VA Secretary Robert McDonald said, “We are ex- In addition to treating veterans, physicians at the refine, test and validate this technology for the benefit cited to further expand our current partnership with center would also treat nonveterans and children with of our patients.” ISM Inside Stanford Medicine October 24, 2016 7 p eo p le Mark Cullen tapped to be senior associate dean for research By Ruthann Richter real sea change.” assembled health, environmental and other records to He said he also hopes to spur the “development of study the environmental and psychosocial causes of Mark Cullen, MD, director of the Stanford Center true team science,” in which researchers from diverse disease in the workforce. In the process, they began to for Population Health Sciences, has stepped into a new disciplines inside and outside the medical school work understand many issues, such as how early life impacts role as senior associate dean for research at the School together on complex problems that impact the risk of disease later in life, and how a of Medicine. human health and longevity. person’s health may be affected by major Cullen will share the responsibilities of the job with “I’m talking about building groups that life changes, such as financial setback. The Harry Greenberg, MD, the current senior associate include, for instance, geneticists and soci- work contributed to important occupa- dean for research, until June 2017. Greenberg will stay ologists and clinical scientists and engineers tional health reforms and helped validate on after that time in a newly created position of associ- — people whose fundamental way of ask- the field of data science. ate dean for research. ing questions is different,” he said. “If we Cullen and Greenberg will serve as “Dr. Cullen came to Stanford in 2009 to serve as are going to answer questions like, ‘What co-principal investigators for the school’s chief of medical disciplines and quickly earned a repu- happens after the moment of conception research activities as part of the National tation as a compassionate clinician, respected mentor that changes your chance of getting disease Institutes of Health’s Clinical and Trans- and collaborative colleague,” Lloyd Minor, MD, dean or being healthy?’ we will need many disci- lational Science Award consortium until of the School of Medicine, said in announcing the ap- plines. Without such diverse teams, we will Mark Cullen May 2017. Cullen will serve as the sole pointment Oct. 5. never understand how social networks do or lead investigator following the grant’s A population scientist and public health expert, Cul- don’t contribute to our health. We will not renewal. len said one of his goals is to build the stature of Stan- understand how living in a complex, urban environ- In announcing the appointment, Minor also praised ford’s program in quantitative sciences, or what he calls ment impacts the way people survive, or why and how Greenberg, a professor of medicine and specialist in the dry-lab sciences. they develop chronic disease and what we might do to viruses affecting the gastrointestinal tract, liver and re- Promoting dry-lab sciences change that. These are questions that require many in- spiratory system. He has had led the school’s research tellectual inputs.” enterprise since 2002. “One of my major ambitions in the new job is to Big data pioneer “Throughout his tenure, Dr. Greenberg has been advance the science culture,” said Cullen, who is also a champion for increased collaboration across the re- a professor of medicine. “I want people to accept the Cullen has been a pioneer in big data; long before search spectrum and across disciplines around the uni- potential of dry-lab research to be an equal partner with the practice became popular, he was using large collec- versity,” Minor said. “He played a key role in helping to what’s historically been fantastic at Stanford, which is tions of data to study human health. In the late 1990s, expand PI waiver privileges to clinician-educators and the laboratory sciences, and to recognize that in fact while at Yale University, he began a longstanding rela- postdoctoral fellows, and I have deeply appreciated his without quantitative science we will never be a great sci- tionship with Alcoa, America’s largest aluminum pro- wise counsel and many contributions to Stanford Medi- ence institution. That culture shift would represent a ducer, in which he and his colleagues from various fields cine and the university.” ISM

Sylvester named an associate dean for maternal and child health

By Erin Digitale dean of the School of Medicine. “He is ciate dean for maternal and child health. His laboratory and clinical research an accomplished clinician, mentor and He will emphasize building on the ex- focus on understanding the biology of Karl Sylvester, MD, has been ap- researcher who will bring his expertise isting infrastructure of Spectrum Child disease in premature and newborn ba- pointed associate dean for maternal and in all of these arenas to the job of ad- Health and ensuring an efficient collabo- bies. Sylvester has established a network child health–research at the vancing scientific investiga- ration with colleagues and stakeholders of academic children’s hospitals and in- School of Medicine. tion in child and maternal at Stanford Health Care and the medical vestigators to discover and test specific An associate professor of health.” school. molecular diagnostics of newborn dis- surgery and of pediatrics, Working in concert with “Karl will assist in developing the eases, such as necrotizing enterocolitis Sylvester takes over the po- co-senior associate deans necessary infrastructure resources to fa- and sepsis. He is widely published on the sition from Mary Leonard, for research Mark Cullen, cilitate translational and clinical research clinical care of necrotizing enterocolitis MD, who is now chair of MD, and Harry Green- in Lucile Packard Children’s Hospital and on his group’s findings on biomark- the Department of Pedi- berg, MD, Sylvester will Stanford for all pediatric investigators ers of disease. atrics. He joins three other focus on aligning the pedi- across the School of Medicine and uni- Sylvester earned a medical degree associate deans for maternal atric and maternal research versity,” Stevenson said. from Jefferson Medical College in and child health who rep- portfolios of the School Sylvester is also medical director of Philadelphia and completed his clini- resent faculty affairs, global Karl Sylvester of Medicine. He will also Packard Children’s Pediatric Trauma cal training at the University of Penn- affairs and obstetrics. serve as a co-leader of Spec- Program, and since 2013 he has been ex- sylvania, Yale-New Haven Children’s “We are delighted to welcome Karl trum Child Health along with Leonard ecutive director of the hospital’s Program Hospital and the Children’s Hospital of to his new role,” said Lloyd Minor, MD, and David Stevenson, MD, senior asso- for Fetal and Maternal Health. Philadelphia. ISM

of note Sex and Gender in Alzheimer’s Disease grant from the two researchers in 2017, recognizes academic leadership Alzheimer’s Association. The grant provides $250,000 that has improved the well-being of children. Stevenson reports on significant honors and awards for faculty, staff and students over three years. She will investigate whether there are will travel to Iowa to accept the award in April. He is a sex differences in the way risk factors interact to affect neonatologist who specializes in neonatal jaundice and the development of Alzheimer’s disease. the prevention of preterm birth. Tandy Aye, MD, was promoted to associate profes- Josef Ruzek, PhD, was appointed professor of psy- Chi-Ho Ban Tsui, MD, was appointed professor of sor of pediatrics, effective Aug. 1. She is a pediatric en- chiatry and behavioral sciences, effective June 1. He di- anesthesiology, perioperative and pain medicine, effec- docrinologist whose research and clinical work focuses rects the Dissemination and Training Division of the tive Aug. 1. ISM on how blood glucose values and sex hormones affect U.S. Department of Veterans Affairs National Center children’s brains. for Post-Traumatic Stress Disorder . Alistair Boettiger, PhD, was appointed assistant Chiara Sabatti, PhD, was promoted to professor of professor of developmental biology, effective Sept. 1. biomedical data science and of statistics, effective Aug. His research uses single-molecule microscopy to under- 1. She develops statistical methods to uncover the mo- stand how noncoding sequences in the genome interact lecular basis of disease, using large heterogeneous data physically to shape genome structure and regulate gene sets. expression. David K. Stevenson, MD, the Harold K. Faber Pro- Joachim Hallmayer, MD, was promoted to profes- fessor of Pediatrics and senior associate dean for ma- sor of psychiatry and behavioral sciences, effective July ternal and child health, will receive the 2017 Frank H. 1. His research focuses on the genetics of autism and Morriss Jr. Leadership Award from the University of narcolepsy, as well as on the genetics of disorders such Iowa Carver College of Medicine. The honor, given to Tandy Aye Alistair Boettiger as 22q11 deletion syndrome and Turner syn- drome that can cause neuropsychiatric problems. Ramasamy Paulmurugan, PhD, was pro- moted to associate professor (research) of radi- ology, effective Aug. 1. His research focuses on developing new therapies for triple-negative breast cancer, a form of cancer that lacks three types of receptors and has no targeted therapies available for treatment. Natalie Rasgon, MD, PhD, professor of psy- chiatry and behavioral sciences, has received a Joachim Hallmayer Ramasamy Paulmurugan Natalie Rasgon Chiara Sabatti David K. Stevenson 8 October 24, 2016 Inside Stanford Medicine