Medicine SPRING 2013

medicine SPRING 2013

A NEW ROLE FOR A NEW TIME 12

ENDING THE BIG SLEEP putting the brakes on one woman’s endless sleeping

TRANSFORMING MEDICINE IN ANOTHER GEORGIA Emory internist Ken Walker is on a mission

THE HEALING HORMONE using progesterone to mitigate brain injury in stroke and brain tumor patients THE NEW DEAN 12 Christian Larsen has been a college student, medical student, clinician, and

contents faculty member, all at Emory. Now he takes on the deanship of the medical school.

2 EMORY MEDICINE medicine SPRING 2013 3 8 18

Editor DEAN’S MESSAGE 2 Kay Torrance IN BRIEF 3 Art Director Peta Westmaas ENDING THE BIG SLEEP 8 Graphic Designer Linda Dobson Emory doctors put the brake on one woman’s endless sleeping Director of Photography and found a new treatment for a widely misunderstood condition Jack Kearse By Quinn Eastman Production Manager Carol Pinto A NEW ROLE FOR A NEW TIME 12 Executive Director, Health Sciences Creative Services Emory transplant surgeon Christian Larsen steps up as dean Karon Schindler and has big plans to integrate the health sciences. Associate Vice President, Health Sciences Communications By Rhonda Mullen Vince Dollard TRANSFORMING MEDICINE IN ANOTHER GEORGIA 18 Dean, Emory University School of Medicine Six thousand miles away from Emory, internist Ken Walker Christian Larsen is helping to transform medicine. Please send address changes and letters to the editor to: By Dana Goldman Editor, Emory Medicine Emory University THE HEALING HORMONE 22 School of Medicine 1440 Clifton Road, NE, Suite 150 Donald Stein finds vindication in his long-held belief that Atlanta, GA 30322 progesterone is more than just a female hormone. Phone: 404-727-6799 Email: [email protected] By Martha Nolan McKenzie Email for class notes: [email protected] CLASS NOTES 24 Visit us online at emorymedicinemagazine.emory.edu Emory Medicine is published by the School of Medicine, a component of the Woodruff Health Sciences Center of Emory University, emoryhealthsciences.org. Articles may be reprinted in full or in part if source is acknowledged. Persons not on the mailing list can order a one-year sub- scription by sending a check for $20 (made out to Emory University) to the editor. © Fall 2012. 212019-2 (Not the) Dean’s Message

In our backyard, a home-grown talent

This space usually is reserved for a few words from the dean, but as this issue marks a transition in leadership of the School of Medicine, please allow me to borrow it to introduce our new dean, Dr. Christian Larsen. I take considerable pride in the fact that Dr. Larsen (Chris) is an alumnus of Emory. He graduated from Emory College in 1980 and from the medical school in 1984, and he completed postgraduate training at Emory, and also at Stanford and Oxford, in surgery and transplantation. I am proud too that Chris decided to pursue his career at Emory. He joined the faculty in 1991 and became founding director of the Emory Transplant Center in 2001 and chair of surgery in 2009. Dur- ing his time here, he has earned great respect not just for remarkable accomplishments (see article on page 12) but also for his collaborative spirit and ability to lead by example. Because he has seen Emory from so many perspectives—as student, resident, teacher, researcher, surgeon, and administrator—no one knows more about the school’s strengths, challenges, and potential in all its missions than Chris Larsen does. Nor is anyone better suited to help shape the school’s culture to meet present and future needs. At Emory and at other academic medical centers throughout the country, we are facing unprecedented change that will significantly affect all of our missions. We are facing financial constraints and changes in national policy that will impact the new discoveries needed to improve health as well as training for the next generation of health professionals. For our medical school to thrive, we need a visionary leader who can approach this new environment with creativity and in an integrated fashion, one who has the courage to do more with less by focusing on areas where we can have the most impact, one who can bring together teams of professionals to solve these big challenges. That person is Chris Larsen, our new dean of medicine, vice president of health center integration in the Woodruff Health Sciences Center, and chair of the board of the Emory Clinic. With his passion and dedication to service, he epitomizes the principles of our benefactor Mr. Robert W. Woodruff. He is the right leader for this time.

S. Wright Caughman Executive Vice President for Health Affairs CEO, Woodruff Health Sciences Center Chairman, Emory Healthcare

2 EMORY MEDICINE In Brief

$8.3M grant for Autism Center of Excellence links Atlanta partners Who gets CPR?

new Autism Center of Excellence (ACE), funded by Residents living in high-income an $8.3 million grant from the National Institutes white and high-income integrated of Health (NIH), will create a comprehensive neighborhoods were more likely to Aresearch effort among the Marcus Autism Center at receive bystander CPR during an out- Children’s Healthcare of Atlanta, the medical school’s of-hospital cardiac arrest than arrest Department of Pediatrics, and Yerkes National Primate victims in low-income black neighbor- Research Center at Emory. The ACE is one of only three such cen- hoods, according to a publication in ters nationwide and brings together more than 25 researchers and phy- the Oct. 25 issue of the New England sicians in eight laboratories in the three Atlanta institutions, along with Journal of Medicine. Arrest victims in low- collaborators at Florida State University. income white, low-income integrated, and The ACE will study risk and resilience for autism in infants and high-income black neighborhoods were also toddlers and develop new screening programs in early infancy. The less likely to receive bystander CPR. ACE also will create new community-based health care for infants and In an effort to look at future CPR train- toddlers with autism spectrum disorders (ASD). ing processes, researchers from Emory The first two ACE research projects will focus on social visual University, the University of Colorado, and engagement and social vocal engagement in ASD, building on earlier several other institutions wanted to better research first conducted by ACE director and Georgia Research Alliance understand the effects of different neigh- scholar Ami Klin and collaborators Warren Jones and Gordon Ramsay, borhoods on the probability of receiving both of Emory’s Department of Pediatrics. Eye-tracking studies of social bystander CPR in out-of-hospital cardiac engagement and biological motion in adolescents, toddlers, and infants arrests. More than 300,000 out-of-hospital have already uncovered factors that are predictive of ASD in the first six cardiac arrests occur in the United States months of life. each year. Recent work with social visual engagement compared typical Using surveillance data submitted from infants and infants at risk for ASD. Marcus Autism Center will fol- 29 U.S. sites to the Cardiac Arrest Registry low these infants from birth with new tests of social visual and vocal to Enhance Survival (CARES), the research- engagement measured through “growth charts” comparing normal ers looked at data from 2005 through social engagement and deviations in the first year of life. 2009. Out of 14,225 usable cardiac arrests Another research project, at Yerkes Research Center, registered in CARES, bystander CPR was will study behavior in rhesus macaques, connecting provided to 4,068 patients. eye-tracking behavioral studies of social visual The CARES program was developed by engagement and growth charts of social engage- Emory’s Department of Emergency Medicine ment along with genetics, behavioral, and brain and has been funded by the Centers for imaging studies in nonhuman primates. Disease Control for the past eight years.

SPRING 2013 3 In Brief Overcoming ‘original sin’

cientists studying flu vaccines have identi- range of hosts, such as pigs and birds, and because its genome fied ways to overcome an obstacle called is flexible, says Joshy Jacob, an Emory microbiologist. “original antigenic sin,” which can impair “Original antigenic sin is really a reflection of the immuneS responses to new flu strains. agility of the influenza virus,” he says. “OAS becomes a factor Original antigenic sin (OAS) occurs when the immune when the new circulating strain is a ‘drifted’ version of what system encounters one viral strain and then a related came before. The old antibodies can’t neutralize the new one, but can only respond by making antibodies new virus, and that helps the new virus survive.” against the first strain, resulting in a less effective Jacob and colleagues demonstrated that com- defense. bining the immunization with a vaccine addi- Researchers at the Emory Vaccine Center have tive allows mice to respond better to the live demonstrated in experiments with mice virus. The adjuvant is a squalene oil-in- that OAS can be overcome by using a water emulsion. Squalene is a vaccine vaccine additive or by repeated immuni- additive licensed in European countries zation with the second viral strain. since the 1990s but is not approved for The findings could be important use in the United States. in vaccination of people with weaker “It appears that the adjuvant is mak- immune systems, such as those with ing the immune responses to the first chronic infections, young children, viral strain broader, so that a wider or the elderly. range of antibody-producing cells are The influenza virus has become so able to respond to the second strain,” widespread because it can infect a wide Jacob says.

Two Emory hospitals awarded top 10 status by University HealthSystem Consortium

The University HealthSystem Consortium (UHC), national quality measurement system available an alliance of 119 academic medical centers and for teaching hospitals. 291 of their affiliated hospitals, ranked Emory “The main reason these rankings are University Hospital (combined with Emory important is that they are indicative of our University Orthopaedics & Spine Hospital) significant improvements in achieving high second and Emory University Hospital Midtown survival rates, infection rate reductions, sixth in the 2012 UHC Quality Leadership Awards. substantial reduction of ventilator-acquired This is the first time UHC has had two hospitals pneumonia, and many other quality, safety, from one health care system rank in the national efficiency, and patient service indicators,” top 10. The UHC rankings are traditionally looked says John Fox, president and CEO of upon as providing the best, most non-biased Emory Healthcare.

4 EMORY MEDICINE Immune system compensates for ‘leaky gut’ in IBD susceptibility

ew research could clarify how inflamma- ed certain types of immune cells. They found that CD4+ T tory bowel diseases (IBDs) develop. immune cells are needed to produce signals that encour- “Our study results suggest that when there age production of the antibody IgA, which limits incur- isN a chronically leaky intestine, defects sions by bacteria in the intestine. in the immune system need to be pres- “In normal mice, immune cells JAM-A deficient mice ent for the development of IBD,” says such as CD4+ T cells and IgA-producing Emory pathologist Charles Parkos. have a “leaky gut,” mean- B cells do not play a big role in DSS- “Breakdown of the intestinal barrier can ing that chemicals and triggered colitis,” Denning says. occur as a result of intestinal infections “But if the mice have a preexisting bacteria can cross more or stress. The normal response involves leak, the immune system plays an several components of the immune sys- easily from the insides important role.” tem that help to heal the injury while of the intestines to the While defects in the production controlling invading bacteria. When of IgA alone do not result in colitis, rest of the body. this normal response is defective and the presence of a chronically leaky gut there is a leaky barrier, the risk of devel- along with an IgA deficiency results in oping IBD is increased.” increased susceptibility to abnormal intestinal inflam- Parkos and his colleague, pediatrics researcher Tim mation. During intestinal inflammation, the amount of Denning, have been studying mice that are deficient in a JAM-A in the epithelium can decrease, further weakening protein called JAM-A (junctional adhesion molecule A). the intestinal barrier. JAM-A is an important regulator of the epithelial bar- “There is a ‘chicken or the egg’ question with respect rier in the intestine. Denning describes JAM-A and other to whether inflammation or alterations in the intes- “tight junction” molecules as forming a seal between epi- tinal barrier come first,” Parkos says. “Many thelial cells like a zipper, which keeps bacteria away from people with IBD report that their first severe the rest of the body. episode was brought on by a stressful event or JAM-A deficient mice have a “leaky gut,” meaning that an intestinal illness, and it is possible chemicals and bacteria can cross more easily from the that these events serve as a trigger that insides of the intestines to the rest of the body. Passage of starts a vicious cycle of altered barrier bacteria across the intestinal wall and into the body can and inflammation.” cause inflammation and disease. JAM-A deficient mice —Quinn Eastman have more bacteria in the liver and lymph nodes and are more susceptible than regular mice to a chemical treatment (DSS) that induces colitis. “This is a situation that may be analogous to first degree relatives of people with Crohn’s disease,” Parkos says. “Some of these people have increased intestinal per- meability, which suggests that they are more susceptible to developing disease, but they don’t get sick. Gut perme- ability also transiently increases in normal people based on what we eat and drink, yet disease doesn’t occur. We think that immune compensation is what protects the body under these conditions.” The researchers wanted to dissect which types of immune cells were responsible for this effect so they treated JAM-A deficient mice with antibodies that deplet-

SPRING 2013 5 In Brief New lead on drugs Study clarifies benefits of against Parkinson’s coronary stents

disease Who should get stents to keep Mavromatis says. “I think FFR will once-clogged coronary arteries play a bigger role in evaluating and Emory scientists have identified a compound open? Someone who is having a treating coronary artery disease, that boosts the survival of neurons threatened by heart attack certainly should, and as it can direct stenting much more

Parkinson’s disease. The compound, bis-3-cog- the life-prolonging @A:; precisely than angi- nitin, could be a starting point for finding drugs benefits have been ography toward clini- Researchers used that delay Parkinson’s disease progression. demonstrated in several cally important coronary In mice, bis-3-cognitin could protect neu- studies. But results have a technique called artery disease, improv- rons from damaging toxins and from devel- been more ambiguous fractional flow ing outcomes and sav- oping motor problems when it was given for patients who have reserve (FFR) to ing money.” together with the toxin. stable angina. decide if someone The FFR procedure Zixu Mao, an Emory pharmacology An Emory study by costs several hundred with stable angina researcher, and his colleagues had been Kreton Mavromatis, dollars but is significant- studying MEF2D, a protein vital for the sur- director of cardiac should receive a ly less expensive than vival of neurons. Mao’s previous research catheterization at the stent or medical a coronary stent. Habib had shown that MEF2D is altered in the Atlanta VA Medical therapy with drugs Samady, director of neurons of people with Parkinson’s disease. Center, showed patients such as aspirin interventional cardiology with stable angina who at Emory, also has been The MEF2D protein is sensitive to cellular and statins. received stents along an advocate for the use changes, such as oxidative stress, which can @A lead to neuron damage in Parkinson’s. with medical therapy of FFR to select who “For years, we had been talking about were less likely to be hospitalized would benefit from a coronary stent. looking for drugs that enhance MEF2D,” Mao than those receiving only medical “At Emory, we are sometimes says. “The challenge was how to set up a therapy, 4% versus 13%, respec- asked to reevaluate patients who screening system.” tively. have been slated for coronary Bis-3-cognitin appears to have been a In the study, researchers used artery bypass surgery at another good catch. Cognitins are a family of com- a technique called fractional flow hospital where recommendations pounds derived from tacrine, the first drug reserve (FFR) to decide if someone are made based on angiography approved by the FDA to treat the symptoms of with stable angina should receive alone,” says Samady. “When we Alzheimer’s disease. Tacrine was eventually a stent or medical therapy with evaluate these cases using FFR, we discontinued because of liver toxicity and drugs such as aspirin and statins. are sometimes able to recommend other side effects. Conventionally, X-ray coronary angi- courses of treatment that involve Bis-3-cognitin could protect cells in ography is used to assess the need fewer stents or even medical culture by increasing MEF2D levels. It also for a stent. FFR involves introducing therapy. Occasionally, based on FFR protected against the toxin MPTP, which a pressure sensor via guidewire into data, we send our patients for an kills neurons. the coronary artery, to measure how endoscopic or ‘minimally invasive’ “We think MEF2D is not the only target much blood flow is being blocked. bypass and stent the remaining of bis-3-cognitin,” Mao says. “It is a potent Some cardiologists have narrowings.” antioxidant, but MEF2D is required for the criticized the results, noting that the A large, multi-center study neuroprotective activity—we found that if benefits of stenting didn’t reduce called ISCHEMIA is starting that you knock down MEF2D in cell lines, the deaths and heart attacks. will address the coronary stent protective effects are much weaker.” “It is important to recognize versus medical therapy issue in a He adds that bis-3-cognitin also appears that reducing symptoms of angina more definitive way. Both Emory and to avoid the acute toxicity problems of and the chance of hospitalization is the Atlanta VA Medical Center are tacrine. a tremendous benefit to patients,” participating.

6 EMORY MEDICINE New gene for Alzheimer’s risk identified

esearchers of the Icelandic population for ApoE E4, a percentage that is have identi- higher in other countries. People who carry the variation and fied a genetic do develop Alzheimer’s disease do so roughly three years ear- variationR that may lier than non-carriers. Although rare, the variant is important indicate an increased because it adds to a growing list of genes linked to Alzheimer’s risk for late-onset disease, and it provides clues to causal mechanisms. Alzheimer’s disease. “First, the results demonstrate that certain rare genetic The finding is a result variants can have a strong influence on Alzheimer’s disease of a collaboration between risk for individuals carrying those variants,” says Allan deCODE genetics in Levey, director of Emory’s Alzheimer’s Disease Research Iceland and Emory Alzheimer’s researchers. They read the Center and chair of neurology. “Second, since the TREM2 entire genomes of 2,261 Icelanders. gene is expressed in microglia and other immune cells The new variant increases risk by about a factor of three, where it triggers production of inflammatory cytokines, the an effect that is similar in scope to that of the most com- finding provides growing evidence that chronic inflamma- mon genetic risk factor for Alzheimer’s, ApoE E4. However, tion is relevant for the development of the disease, and that the new variant, called TREM2, is rarer: it is found in one in modulating TREM2 signaling and microglial function is a every 160 people in Iceland, compared with more than 17% potential therapeutic strategy.”

Targeting inflammation to treat depression

esearchers at Emory molecule in inflammation that has have found that a medi- been shown to be elevated in some cation that inhibits depressed people. inflammationR may offer promise Study participants all had major for people with difficult-to- depression and were moderately treat depression. resistant to conventional antidepres- Prior studies have suggested that sant treatment. Each participant was depressed people with evidence of assigned either to infliximab or to a high inflammation are less likely to non-active placebo treatment. respond to anti-depressant medica- When investigators looked at the C-reactive protein. tions and psychotherapy. This study results for the group as a whole, no “The prediction of an antide- was designed to see whether block- significant differences were found pressant response using a simple ing inflammation would be a useful in the improvement of depression blood test is one of the holy grails treatment for people with difficult- symptoms between the drug and in psychiatry,” says Andrew Miller, to-treat depression or only those placebo groups. However, when senior author of the study and the with high levels of inflammation. the subjects with high inflamma- Timmie Professor of Psychiatry and The study employed inflix- tion were examined separately, they Behavioral Sciences. “This is espe- imab, used to treat autoimmune exhibited a much better response cially important because the blood and inflammatory diseases such as to infliximab than to the placebo. test not only measured what we rheumatoid arthritis and inflam- Inflammation in this study was mea- think is the root cause of depression matory bowel disease. Infliximab sured using a simple blood test that in these patients but also is the tar- blocks tumor necrosis factor, a key is readily available and measures get of the drug.”

SPRING 2013 7 How Emory doctors put the brakes on one woman’s endless sleeping and found a new treatment for a widely misunderstood condition

8 EMORY MEDICINE Ending the big sleep

By Quinn Eastman • Illustration by Christiane Beauegard

leep was consuming Anna Sumner’s life. The Atlanta attorney S routinely slept 16 hours every day, and it never felt like quite enough. She needed multiple alarms to wake up and could sleep through a phone ringing or someone shaking her. When she came to Emory Sleep Center in 2005, she told doctors there that she “craved” sleep all the time.

“It came to the point when faced with a choice between But along the way, Rye discovered the scientific community sleeping and eating, I would rather sleep,” she recalls. “But wasn’t as convinced as he was about his discovery. when I did sleep it was not restorative.” Sumner’s care team had considered and ruled out com- The ‘Sumner stupor’ mon causes of sleepiness, such as sleep apnea and narcolepsy. Sumner says her sleep demands increased in high school. The typical drugs of choice to combat sleepiness, prescription While she was studying at Princeton, her parents in Missis- stimulants, didn’t help. This was a type of sleep disorder that sippi became more concerned because she’d spend much of they did not know how to treat. her holidays at home asleep. During law school, a flexible “It required a shift in thinking,” says neurologist David schedule allowed her to conceal her sleep requirements. As Rye, who has led the effort to understand Sumner’s mysteri- an attorney, she says she never missed a critical legal appoint- ous condition. “Usually if people are having trouble staying ment, although the strain became difficult to bear. Over the awake, the conventional thought is that their brains are defi- years, she kept a list of “things I slept through,” like a friend’s cient in excitatory monoamines, like histamine or dopamine, wedding she had traveled across the country for. She man- and are in need of a jolt from these wake-promoting neu- aged to keep a sense of humor about her situation, joking rochemicals. In Anna’s case, giving her extraordinary doses with her brothers about the “Sumner stupor.” of stimulants was like trying to drive a car with the parking When Sumner came to Emory’s sleep clinic, Rye and brake on. We needed to release the brake, rather than push his team diagnosed idiopathic hypersomnia and prescribed the gas harder.” her stimulants, such as modafinil and amphetamines. These Sumner’s condition would lead Rye and his team on one drugs proved beneficial for a while. However, the increas- of the most demanding—and rewarding—scientific journeys ing doses needed to sustain the effect made Sumner feel they’ve had. In the end, they were able to put a name to her “twitchy,” elevated her blood pressure, and suppressed her condition and track down the world’s first treatment for it. appetite. And she began experiencing crashes. Unpredictably,

SPRING 2013 9 she would sleep for 30, even 57 hours at a stretch. hand in emergency departments for benzodiazepine overdos- “That was the scary part,” she says. “If I went to bed, I es. When Jenkins added the flumazenil on top of Sumner’s didn’t know if I’d fall off the map and wake up two days later.” sample, it nearly reversed the effects. That led to the question: She took a leave of absence from her job, and her mother would it accomplish the same feat in Sumner? had to move in with her to wake her so she could eat. “We had never had a patient quite like her before,” says The eye-opening moment former Emory nursing sleep specialist Kathy Parker, who is Flumazenil is known to provoke seizures in people going now at the University of Rochester. “I thought to myself that through benzodiazepine withdrawal, so the team decided to she’s going to sleep her life away if we don’t do something.” give Sumner the drug in Emory University Hospital’s epilepsy unit over the course of two days in June 2007. Sumner oc- Hey, GABA cupied herself with “the world’s most boring video game,” a Parker made a chart of all the signaling molecules in the psychomotor vigilance test that measured her alertness by brain, checking off each one as she and Rye tried different timing how fast she could react to numbers on a screen. The drugs to alter Sumner’s brain chemistry. With the list of team monitored her vital signs and brain waves. When the untried neurotransmitters growing very short, they decided dose reached two milligrams, she exclaimed, “I feel alive!” to look at the brain chemical GABA (gamma-amino butyric “The best way to describe it is that my eyes opened, after acid), an amino acid that calms the nervous system for sleep. being half-closed for so long. It was as if a force grabbed my Sleep-promoting circuits in the brain are thought to use eyelids and pulled them upwards,” she says. GABA. Barbiturates and benzodiazepines, such as Valium and For the researchers gathered around, the moment was Ambien, make neurons respond more strongly to GABA. dramatic as well. Parker enlisted anesthesiology researcher Andrew Jen- “In a matter of days, we went from a biophysical experi- kins, who has been studying since the 1990s how GABA af- ment in the lab to having a real impact on a patient’s life,” fects brain cells, to look at Sumner’s cerebrospinal fluid CSF( ). Jenkins says. “It was certainly one of the highest points in He found a normal level of GABA in her CSF, but her CSF my career.” contained a substance with an amount of GABA-enhancing As exciting as the test result was, the drug’s effect wore activity comparable to someone undergoing oral surgery or a off after a few hours. Since flumazenil rapidly metabolizes colonoscopy who had received a strong sedative. (He did not if swallowed whole, it is usually given intravenously, but find any synthetic benzodiazepines in herCSF .) Sumner would need a formulation that was more convenient. The mystery substance appeared to be working with Parker wanted to reformulate the drug, but it was only ap- her GABA to tamp down her brain’s activity, like an ever- proved to counter overdoses, and there was little supply of the present sleeping pill. But neither Jenkins nor Rye could drug. It had not been manufactured since 2004. figure out what the substance Parker worked with the FDA to secure a compassionate- was in her CSF. use exemption for Sumner and with drug patent holder “Sleep and anesthe- Roche to tap the last flumazenil supply, held in Roche’s labo- sia may share some fea- ratory in Switzerland. Parker also worked with a compound- tures in common, but ing pharmacy to develop a 6-milligram flumazenil lozenge they’re not the same for Sumner to put under the tongue throughout the day. thing,” Jenkins says. Sumner discovered that having the level of flumazenil in her “You don’t wake up system swing too drastically made her nauseous or groggy. feeling satisfied Along with the lozenges, a flumazenil-containing cream ap- after general plied to her forearms before bedtime helped her wake up in anesthesia.” the morning. Jenkins Sumner reported that this regimen finally worked, with wanted to see few side effects. She could drive, something that didn’t feel if the substance safe when sleep was such an overpowering urge. She could was similar to a watch entire television shows for the first time in years. In benzodiazepine short, she had her life back. and tested it against flumazenil, Finding others…and skepticism an antidote kept on His success with Sumner led Rye and his team to examine

10 EMORY MEDICINE CSF samples from other patients who had experienced daytime sleepiness. The sleepiness was severe enough that some had applied for disability and others needed leaves of absence from school or work. Sleep apnea and other conditions that cause daytime sleepiness had been ruled out. “Even when they’re ostensibly awake, these patients report that they feel as if they are walking around in a fog,” Rye says. “They have the reaction times of someone who has Neurologist David Rye, researcher Andrew Jenkins, and patient stayed up all night, all the time.” Anna Sumner. Rye found enhanced GABA activity similar to that in Sumner in their CSF samples. He tested Sumner and six others in a clinical study on the effects flumazenil could have on wake up sleep deprived healthy people? If so, could truck their alertness, measured by a psychomotor vigilance test. drivers, airplane pilots, and medical residents use it to stay Flumazenil improved reaction times and perceived alertness awake? Presented with this idea, Rye threw cold water on it. in all seven, although their responses were not uniform. “We are not the first to think that if you muck around When Rye wrote up the results of his clinical study, his with GABA, you can wake people up,” he says. “The military quest to get his paper published proved to be as long as find- tried out flumazenil on sleep-deprived recruits years ago and ing a treatment for Sumner. A number of journals turned seems to have abandoned it.” him down, citing skepticism about his results. The journals’ Several studies with flumazenil indicate that for most goodwill had been tainted by a similar, but bogus, study in people it has no stimulant effects, even if it has now been Italy in the 1990s. shown to restore alertness in a handful. Rye says this variabil- The Italian neurologists reported that they had identi- ity may have something to do with a patient’s sensitivity to fied patients experiencing a “recurrent stupor” because their sleep deprivation, possibly genetic—his hypersomnia patients bodies produced benzodiazepine-like substances. It was later often have a close relative with similar experiences. revealed that the Italian patients were being given the benzo- Although flumazenil has helped Sumner, it may not be a diazepine drug Ativan covertly. practical long-term treatment for others. The supply of the Rye’s study was finally published in the Nov. 21, 2012, drug is limited. Sumner has about a year’s supply left, and issue of Science Translational Medicine, but not before he no manufacturers so far have expressed interest in taking and Jenkins went to great lengths to show that the unknown up flumazenil. substance was not an artificial benzodiazepine drug taken Rye’s other hypersomnia patients are taking the antibiotic by the patients. Using the latest technology, they scoured clarithromycin. (Sumner says she will probably transition to patients’ CSF samples for benzodiazepines. They also showed this drug once her flumazenil runs out.) This drug came by that the sleep-inducing substance works in situations where way of Sumner herself. After contracting bronchitis in 2010 benzodiazepines don’t. In the lab they demonstrated that the and taking clarithromycin, she found herself with insomnia. substance still works upon GABA receptors that were mutated She called Emory, and soon thereafter, clarithromycin’s ef- and rendered insensitive to synthetic benzodiazepines. fects on GABA were tested in the laboratory. The results were promising, and clarithromycin is now the focus of another The still unknown substance clinical study, supervised by neurologist Lynn Marie Trotti. Rye and Jenkins’ next quest is developing new tests to look Rye and Jenkins say they still have some work to do in for the unknown sleep-inducing substance. What they have convincing their peers that hypersomnia has genuine biology determined so far is that based on its size and sensitivity to behind it, judging from an experience of Sumner’s parents. certain enzymes, the substance could be a peptide, similar to They approached a prominent neurologist [not at Emory] the hormone oxytocin. While the substance is detectable in and described their daughter’s condition, only to be told that blood, its concentrations are much higher in CSF, suggesting she was probably taking drugs recreationally. Some of Rye’s that it is synthesized in the brain. other hypersomnia patients have received diagnoses of narco- “I think the ‘sleepy stuff’ is something that is made by lepsy or depression, but hypersomnia may be more common everyone’s brain in some amount,” Jenkins says. “Either Anna than narcolepsy, he says. and other people like her make more of it, or what they make “Looking back on it, it just demonstrates the good luck is more potent, which is the direction I’m leaning now.” that I had to be dealing with doctors who listened to me,” If the substance is present in all of us, would flumazenil Sumner says. “I am grateful for their perseverance.” EM

SPRING 2013 11 Christian Larsen is the new dean, and he’s got big plans to integrate care, research, and education in the health sciences. A NEW ROLE FOR A NEW TIME

12 EMORY MEDICINE By Rhonda Mullen

Christian Larsen was just a boy when he saw his first patient. He used to accompany his dad, a cardiac surgeon, on weekend rounds to check on patients recovering from coronary bypass surgery. When he got older, he’d enter data from his father’s research studies into a big IBM mainframe, marking the beginning of a lifelong interest in science and technology. The elder Dr. Larsen was unusual for his time. In the 1970s, he already was breaking the mold of a stereotypical surgeon by emphasizing patient care provided by teams. He performed heart transplants and sought out Thomas Starzl, Chris Larsen at his who performed the first successful human liver transplant in 1967, to learn Emory medical school about immunosuppression. (Chris Larsen remembers setting up a reel-to- graduation with his reel projector in his family’s living room so that they could watch a movie of father, a cardiac surgeon. one of his father’s transplants.) While in private practice in Miami, the father Larsen developed a wound care program, and at one point, he even left surgery to pursue a PhD in biology at the University of Miami Medical Center. Larsen’s first mentor, his dad, was willing to take some risks. So, it turns out, is his son. The trajectory of Larsen’s career in many ways resembles that of his father. Described by colleagues across the country as both surgeon extraordinaire and brilliant scientist, Larsen has brought teams of people from many disci- plines to provide the complicated care needed for transplant patients, along with developing a new class of immunosuppressive drugs. After his many successes in both the clinical care and scientific arenas, it seems like destiny that Larsen would be chosen for his new role as dean of the Emory School of Medicine, vice president for health center integration at the Woodruff Health Sciences Center (WHSC), and chair of the Emory Clinic board.*

*Additional titles that Larsen has held include the Joseph Brown Whitehead Professor and Chair of Surgery and the Carlos and Marguerite Mason Professor in the medical school.

SPRING 2013 13 But it wasn’t always so clear to the College, when Larsen had one year ACROSS THE POND AND BACK W. Dean boy who was fascinated by science and of medical school at Emory under Warren, Emory’s chair of surgery at nature and grew up exploring the tide his belt. the time, had given Larsen good advice pools of Miami what he wanted to do. The couple moved into an apart- during medical school: “If you’re go- He thought he might study marine biol- ment, long since torn down, near ing to be a surgeon, you should really ogy, which in his mind meant he could Emory’s campus on Clairmont Road spend your time with the best teachers swim at the beach AND do science. across from Athens Pizza. Already outside of surgery. Pick the best teach- Then Emory happened. While in those early years of married life, ers in areas that will broaden you as Larsen doesn’t remember any particular Clotilde—Cloé to friends—became her a physician.” point of decision during his under- husband’s sounding board. As Larsen’s A year into Larsen’s residency at graduate studies, it became clear to him mother was to his father, she was his Stanford, he got a chance to reconnect that he wanted to be a physician, maybe rock, support, and sanity. “He’s a good with his old mentor. At a conference a pediatrician. talker, and I’m a good listener,” she says. in San Francisco, Warren asked, “How By the time his career landed Chris is everything going?” Larsen answered HIS “CHIEF OF STAFF” As an undergradu- Larsen as chair of surgery at Emory, she enthusiastically. He was great. He loved ate at Emory, Larsen met Clotilde Al- had listened so much that she adopted the training. But when Warren asked, lard Stanley, a psychology major who an unofficial title for herself—Larsen’s “How’s Cloé?,” there was a long pause. had had an international upbringing. “chief of staff.” The fact was, Larsen’s work-life balance Stanley’s mother was Mexican, and her As often happens, Larsen didn’t stay was almost nonexistent, and his wife, father—who died when she was 2—was with the specialty that he had planned at home with baby Nicole, felt isolated. French. Her mom later married an to pursue at the beginning of medical The dean saw an opening and invited American, whose career with the Ford school. Instead, he became more and the young surgeon back to complete

HE THOUGHT HE MIGHT STUDY MARINE BIOLOGY, WHICH IN HIS MIND MEANT HE COULD SWIM AT THE BEACH AND DO SCIENCE.

Foundation took his new family around more interested in surgery. He liked the his residency at Emory. The family the globe. A native Spanish speaker, opportunities that surgery presented started packing. Clotilde learned English at age 9. to make an immediate difference in As a second-year resident, Larsen The exotic beauty caught Larsen’s patients’ health and what he describes came under the tutelage of Emory’s eye at a freshman mixer, and the chem- as its “elegance and beauty.” He began chief of transplant surgery John istry major spent the evening asking her thinking of a career in congenital heart Whelchel in the operating room. He a stream of questions about her high surgery, which would marry his inter- also stayed interested in the science school in Karachi, her travels, and her ests in children and surgery. behind the techniques that he was family. Larsen later told a friend, “One But along the way, nephrologist learning. When an opportunity came day I’m going to marry her.” David Lowance introduced transplanta- along to study in the lab of renowned It took until their senior year for tion into the mix. During his rotation transplant surgeon and immunolo- Larsen to persuade Stanley to go out with Lowance, Larsen noticed a striking gist Peter Morris at Oxford University, with him. Up until then, she thought of difference between patients who had Warren (along with Whelchel and him only as a friend, “a person to go to received a transplant and those on Lowance) once again enabled Larsen if you needed help with something like dialysis. “The restoration of health and to pursue his passion. a flat tire or chemistry homework.” vitality was evident in the transplant The Larsens headed to England, But Larsen’s prediction of marry- patients,” he says. now with two toddlers, for what was ing her one day is indicative of how That observation changed his supposed to be a year of studies that he works. When he sets his mind to course once again, and he applied for a turned into three. something, he can figure out how to residency in general surgery, snagging a A year later, Thomas Pearson, who make it happen. They wed in 1981, coveted slot at Stanford. Larsen’s life was had just finished his surgery residency a year after graduating from Emory about to change again. at Emory, also arrived in Oxford to

14 EMORY MEDICINE study immunology. The two surgeons were in staggered years in training in Atlanta and hadn’t known each other before, but they soon grew to be fast friends. They rode bicycles to work in the mornings while they talked about ongoing projects in their respective labs. Their families had dinner together on Friday nights. To this day, Larsen and Pear- son continue to work together, run Thomas Pearson and Larsen at the retirement party of Peter Morris at Oxford together, and socialize together—espe- University. Larsen studied under Morris, a renowned transplant surgeon and cially now that both families are empty immunologist, known widely as “The Professor.” nesters. As Larsen began as dean of medicine on January 15, Pearson, who is Livingston Professor of Surgery, as- sumed the position as executive director of the Emory Transplant Center. “There is no way that Chris could be doing what he’s doing without Tom’s support,” says Cloé Larsen. “They have each other’s back.” When the surgeons finished their training, earning an MD and DPhil, they each had an offer to have a clinical practice and a research laboratory at Emory. Instead they decided to share both. One month Larsen covered the lab and Pearson, the clinical rotation, and the next month, they switched. They brought complementary skills to the budding partnership. “We both work really hard,” says Pearson. Pearson and Larsen teamed up in covering their research and patient care “But on ideas and strategy, he’s the services. One month, Larsen was in the lab and Pearson on clinical man. My contribution is, well, I’m the rotation. The next, they switched. operations person.” Both felt it was important not only to restore health to seriously ill patients via transplant but also to find better long-term solutions to the immunosuppressant therapy that patients had to take ever after to keep their bodies from rejecting the donor organs. Pearson remembers that they started their lab with an empty room “He’s a good talker, and I’m a good Pearson and Larsen are avid runners and no funding. They wrote their first listener,” says Clotilde (Cloé) Larsen and train together for events such as grant in 1991. “We had an idea that a of her husband. the ING marathon. particular pathway was important in organ rejection and if we blocked that

SPRING 2013 15 pathway, we could create tolerance,” he says. “Our research program was always rooted in trying to ask questions and understand biology in ways that would create new opportunities for treatment,” Larsen says. “The clinical team knew we were not satisfied with the treatments we had today.” Larsen, Pearson, and faculty and staff of the Emory Transplant Center celebrate Within 10 years, Larsen and the publication of their paper on co-stimulation blockade in Nature. Pearson had built a comprehensive transplant center that integrated patient care and research. They were making progress on their understanding of immunity after transplantation. They had developed collaborations with scientists at the Yerkes National Primate Re- search Center and with other disci- plines across the Emory campus. They had redesigned how clinical care was provided to transplant patients. The effort was so impressive in such a short time that Oxford came calling. Morris, whom everyone called “The Professor,” was retiring, and Larsen was offered the chance to take over his program. It gave him pause. There was the chance to enjoy the prestige of Oxford and to step into the big shoes of a mentor he respected. Pearson remembers standing in the rain outside the DeKalb Farmer’s Mar- Larsen takes the reins from former dean Thomas Lawley, who served as dean at ket and taking Larsen’s call about the Emory for 16 years and will remain on the faculty. offer. “You’ve got to come with me,” Larsen told his colleague and friend. Cloé Larsen and his daughters were TEAM TRANSPLANT Larsen’s decision of that success goes back to Larsen’s willing to go. Pearson, his wife, and two turned out to be the right one for fundamental approach to everything he daughters were considering the move. patients, his field, his own career, and touches: building teams. Larsen had a running list of pluses and Emory. It was here that he and Pearson He has collaborated for more than a minuses on whether to go or stay. It tied built a truly interdisciplinary program decade with Rafi Ahmed, director of the both families in knots. Then one winter’s that pulls together surgeons, nephrolo- Emory Vaccine Center and a Georgia day as he walked among the Japanese gists, nurse practitioners, infectious Research Alliance Eminent Scholar, maples that he and Cloé had recently disease specialists, nutritionists, social on protective immunity. TheNIH has planted, Larsen made his decision. workers, and pharmacists to improve repeatedly asked the two how they col- With Pearson, he had built a program the experience for patients. Here that laborate so well, to pass along the model in Atlanta and made relationships that they did the pivotal research that to less amicable research teams. were starting to grow and bear fruit. “In eventually led to FDA approval of a Mandy Ford, a basic bench scientist the end, I couldn’t conceive of starting new immunosuppressant, belatacept, who did her training in autoimmunity over or of making the advancements any that causes less long-term damage at Emory, has been a part of the trans- place else,” Larsen says. He stayed. to kidneys than cyclosporine. Much plant team effort for nine years and at

16 EMORY MEDICINE the university for 14. During that time, ACCEPT NO BARRIERS Larsen takes on his in the teams he puts together. He she’s met frequently with Larsen to talk new roles at Emory at a time of acute respects no barriers, and I mean that science, always feeling more inspired challenges to health care, in particular in a good way.” when she left his office than when she to academic, tertiary medical centers Larsen also has the advantage of al- arrived. Now on the research faculty, that provide care for some of the sick- ready knowing the challenges particu- she has stayed at Emory not only be- est people in the country. Tremendous lar to Emory. But being “home-grown” cause she believes in the mission and downward pressure is being exerted on from his undergraduate years all the the work but also because of her men- the finances of medicine, and changes way through his professional career tor. “People make life decisions about are afoot in the way medical centers could have had a downside. Sometimes where they want to live, raise their and providers are reimbursed. The trainees aren’t taken as seriously when family, and have their careers based on nation is facing a shortage of doctors, they transition at the same institution Chris Larsen,” she says. and while new slots are opening up for from resident to fellow or fellow to fac- Andrew Adams, who also studied medical students, the number of resi- ulty member. When Larsen was named with Larsen as an MD/PhD student, re- dency positions are not keeping pace. chair of surgery in 2009, some of the turned to Emory as a transplant surgery Research opportunities have never faculty in his department were his fellow after a residency at Massachusetts been better in some respects, but the teachers in medical school. “I learned General Hospital—in part because of NIH most likely is facing a budget that that that’s okay,” he says. “The relation- Larsen. “He’s a good person to emulate will stabilize or decline. ships have been great, and people have as a surgeon, scientist, and family man,” In light of such challenges, why been supportive.” says Adams, who helped start Emory’s would Larsen want to take on the As Larsen considered applying to islet transplant program to cure diabetes. deanship? He laughs when asked, succeed Tom Lawley, who had served “There are a lot of good and smart men- but his answer is serious. “It might for 16 years as dean of Emory’s medical school, he turned as usual to his two sounding boards—his wife “HE RESPECTS NO BARRIERS, AND I MEAN and “chief of staff” and the man who has had his back all these years, THAT IN A GOOD WAY.” –Wright Caughman Tom Pearson. Through more than 30 years of mar- tors, but he really champions people. He be more comfortable to stay in my riage, Cloé Larsen has come to know is there to help you succeed, and there is current roles, which are challeng- her husband as a hard worker with “a lot no hint of being in it for his own good.” ing enough. But I feel a broad desire of drive, energy, and vision.” She’s fully Larsen recruited another team to serve people, to share what we’ve on board with his new roles, even with member, Heather Hamby, for the trans- learned in the transplant center and the higher profile and the inevitable plant center’s strategic planning effort. surgery to help Emory rise to meet the entertaining role that comes with being She came to know him as someone who challenges of today’s environment.” the wife of an Emory dean. “I’m all for respected and valued the perspectives of Larsen’s new role also carries the it as long as I don’t have to cook,” she everyone on the team. However, she did title of vice president for health center jokes, “and you can quote me on that.” discover a challenge in trying to keep up integration, a function that Wright Pearson believes that his best friend with him. “He is someone of enormous Caughman, Emory’s executive vice and collaborator is up to the challenge energy and someone who pushes,” she president for health affairs, describes of these new jobs in this new time. “The says. “For example, when we ran out of as looking holistically at the medical amazing thing about Chris is that he space for the program in Emory Hospi- enterprise and working closely with is so incredibly competent in diverse tal, Dr. Larsen set his sites on the sixth Emory Healthcare. “The new environ- arenas and can switch from one to floor of Clinic B. Never underestimate ment requires creativity and courage another easily. He can go from discuss- his ability to persuade and convince,” and someone who can focus us on the ing state-of-the-art bench immunol- she says. Larsen convinced the admin- areas where we can have the biggest ogy to analyzing complex financial istration to let him take over the found impact,” he says. “Chris embraces spreadsheets, to showing great clinical space, and the Mason Trust donated the that. He’s a good leader who instills judgment in the operating room. Being support for the renovation to keep the confidence in others and coalesces dean will be very challenging. I’m glad transplant program growing. what he learns to create a synergy we have Chris to do it.” EM

SPRING 2013 17 Radiologist Patricia Hudgins reviewsWalker a head CT enlisted scan with anyone he could her Ethiopian colleagues. to help with the effort. Countless

Emory faculty and students found

themselves conducting workshops

on health care policy and administra-

tion, analyzing health outcomes, and

helping Georgians lobby for health

care reform.

Photographer Uriel Sinai/Getty Images 18 EMORY MEDICINE Transforming medicine By Dana Goldman in another Georgia

Six thousand miles away from Emory, internist Ken Walker 56Ox 58C 63M was in the “other” Georgia—the former Soviet territory—when the bombing started in August 2008. Ten- sions with another region had escalated, and Georgia had begun exchanging fire with the breakaway region of South Ossetia and Russia. Staying in Tbilisi, Georgia’s capital city, Walker watched as hundreds of casualties streamed into Central Republican Hospital. The H. Kenneth Walker Walker, deputy chief of medi- Resident Education Fund S cine at Grady Hospital, would was established to help residents travel to educational learn that the hard work of conferences, buy equipment, Emory physician faculty in and conduct research. Joseph Overton Jr. 88C 92M helped Georgia had paid off. Only establish the fund. “In months before, 17 of Georgia’s Photographer Vano Shlamov/Getty Images hindsight, Walker’s tugging doctors had completed a mini- and pushing of the residents helped us all reach the next residency program in emergency medicine under the tutelage level. Hopefully this fund will of Emory faculty. Until the group’s graduation, the specialty help continue his teaching of emergency medicine had been nonexistent in Georgia, excellence,” Overton says. For more information on the fund, a country of more than 4 million people. By the end of the please contact Alicia Kanjira at Russo-Georgian conflict a few weeks later, the newly anointed 404-727-3989. emergency medicine doctors cared for hundreds of casualties with only a few deaths.

SPRING 2013 19 Georgia’s new specialty of emergency medicine proved its usefulness. And Walker’s project, which he named Partners for International Development (PfID), gained more momentum in its quest to transform health care in a developing country nine time zones away.

‘Where’s Tbilisi?’ The story of how Emory came to have a presence in Georgia goes back more than 20 years. It was 1992, less than a year after the fall of the Soviet Union, when a former Emory medical dean made a late-afternoon phone call to

Walker. Photo by Chris Hondros “Do you want to go to Tbilisi?” the dean asked Walker with little preamble. “Sure,” Walker said. “Where’s Over the next decade, Walker the Soviet Union imploded, the factory Tbilisi?” enlisted anyone he could to help with rusted and stopped.” Iodized salt stimu- The newly independent Georgia and the effort. Countless Emory faculty lates thyroid functioning. Once the its capital city, Tbilisi, were struggling and students from throughout health problem was discovered, Emory worked economically amid social unrest. De- sciences found themselves conducting with Georgian public health officials to spite a glut of doctors, health care was workshops on health care policy and find a new supply. deteriorating, with basic supplies like administration, analyzing health out- thermometers available only sporadi- comes, and helping Georgians lobby for Teaching the teacher cally. Nurses with only a high school health care reform. When faculty mem- For the past four years, Emory and PfID level of education worked more like bers saw that Georgian medical libraries have held a mini-residency program in assistants than professionals in their were stocked with outdated resource emergency medicine for doctors and own right. guides in Russian, they developed a training programs for practicing nurses Concerned that the health care of multimedia library equipped with with funding from the U.S. Agency for millions would spiral downward, the computers and high-speed internet and International Development, George U.S. State Department created a pro- a generator to ensure usability during Soros’s Open Society Foundations, the gram to match American hospitals daily electricity outages. B. Wardlaw foundation, and others. and medical schools with their counter- During the academic year, Georgian Doctors and nurses train at a learning parts in the former Soviet Union. students received training in Emory’s center in Tbilisi established by PfID Soon Walker and other Emory doctors schools of medicine, nursing, and in 2009 that is furnished with modern from Grady Hospital and from public health. In the summers, Emory medical simulation equipment and Morehouse School of Medicine were medical, nursing, and public health now employs 30 Georgians. So far, 17 flying to Georgia. students traveled to Georgia to conduct emergency medicine physicians and “Our charge was to identify one research studies. One Emory student thousands of nurses have been trained particular hospital and help it. We analyzed the placenta blood of Georgia by PfID. visited individual hospitals and medical newborns and discovered significant The train-the-trainer philosophy is schools. They had about 27 institutes— thyroid deficiencies in more than 60% central to PfID’s plan. “The approach the institute of surgery, of trauma, of of the babies. The problem hadn’t that Emory has taken in Georgia has internal medicine,” Walker says. existed in Soviet times, and Emory doc- been heavily oriented on education,” At the end of the trip, Walker made tors soon discovered why. says Archil Undilashvili, a native a decision: “I decided that the partner- “It turned out that in the Soviet Georgian who serves as PfID’s director ship needed to be with the country Union there was a salt factory that pro- of programs and director of research rather than with an individual hospital.” duced iodized salt,” says Walker. “When programs in Emory’s Department of

20 EMORY MEDICINE Medicine. “Starting with full-time cation. Each lesson interweaves themes nursing faculty, collaborating to create involvement, we gradually shift down familiar to students at Emory, such as intensive curricula to enhance nursing and put our local colleagues in charge, leadership, scholarship, and societal skills and knowledge. “We have about although we keep in systematic contact responsibility. 50% didactic work, and then the rest is with them. Because what we saw is Emory oncologist Mary Jo Lecho- split between simulations and clinical that we can make much longer-term wicz was part of a group that flew to sessions,” reports Undilashvili. “We’ve changes if we base our work on educa- Georgia this past fall. For seven days worked with Georgian nurses on simple tion rather than just doing point-and- she met with faculty and students to hand-washing practices, taking care of shoot temporary work.” support curriculum development for bedsores, how to clean the patient and Walker adds, “The principle that’s the country’s medical schools. There, equipment, and how to be a nursing been so important to us is to educate Lechowicz came to appreciate some of leader and create a successful nursing the people of Georgia so that from then the challenges that come with a cross- service and structure.” on they could educate their own people, cultural collaboration. “One of the Since 2009, more than 3,200 nurses and education by itself will open whole students asked us, ‘How many times a around the country have taken the new professional opportunities.” day do you lie?’ because in their culture intensive training, including Georgia’s The emergency medicine residency the patient doesn’t always know the di- first lady, Sandra Roelofs. “All the health is popular with doctors, who recog- care providers now are asking nurses nize the specialty as a way to get a leg to take our courses,” says Stvilia. “They up in a country with an abundance of do not hire a new nurse if she does not physicians. Says Ketevan Stvilia, the have our certificate. There’s a huge de- Georgian point person for PfID, “They mand in regions with new hospitals.” are very happy because they are able to practice something different. Demand Georgians helping Georgians for them is very high. Now large hos- Georgians have taken notice of Emory’s pitals are opening emergency depart- role in improving their country’s de- ments, and they are the heads of these velopment. Through the partnership, departments.” more Georgians have come to Emory Over the past year or so, no fewer PfID’s new learning center opened in for degrees than to any other university than 75 new small hospitals have been 2012 and has approximately 24,000 in the United States. Some, includ- built around the country. “All of them square feet of space. ing Undilashvili, have joined Emory’s have emergency departments, but they faculty and staff. don’t have the personnel to practice And so when Georgians decided emergency medicine,” says Stvilia. For agnosis,” she says. “It’s a totally different a few years ago to create a national that reason, a large health insurance way of processing the doctor-patient training center for health care workers, company in Georgia recently contract- relationship.” they modeled it after PfID’s own new ed with PfID to provide the residency PfID, along with Emory’s Nell learning center and asked the nonprofit program to its doctors in rural areas Hodgson Woodruff School of Nursing, to establish courses and curriculum. around the country. started the country’s first-ever continu- “Emory’s name is very big here,” says ing education program for nurses in Stvilia. “That’s why they decided to New curricula 2009. Until then, nurses were given have Emory in charge of this new PfID is currently piloting a new curric- little respect or responsibility. Walker national training center because of the ulum at Tbilisi State Medical University, explains, “Nurses were trained after good reputation and confidence that following Emory’s lead on a number the ninth or 10th grade of high school. Emory can do it.” Georgia wants all its of fronts: exposing medical students to There was not very much of a clinical physicians, about 21,000 in all, to take clinical work early on, emphasizing the component to their education,” he says. part in training there; a new contract importance of communication skills, As such, this left doctors to do what’s between the Georgia government and and exploring the role of the doctor- typically considered the job of nurses in Emory was signed in September. If PfID patient relationship, says project leader most developed countries. continues on its path, the two Georgias Gordon Churchward, the medical PfID trained eight local nurses and will have more in common in terms of school’s assistant dean for medical edu- eight local physicians to serve as local health care and health outcomes. EM

SPRING 2013 21 ww

The healing hormone Donald Stein finds further vindication in his long-held belief that progesterone is more than just a female hormone

By Martha Nolan McKenzie

f Don Stein were the kind of man who listened to what others said, I he would have shut down his lab years ago. The Emory neuroscientist spent more than two decades investigating progesterone as a treatment for traumatic brain injury (TBI)—a pursuit that was unappreciated at best and maligned at worst. A naturally occurring hormone was too simple a solution to too complex a problem, according to the prevailing wisdom. Today Stein stands if not on the threshold of vindication, at least within the general neighborhood. After better-than-hoped-for results from the first human trial, progesterone is being tested in two nationwide phase 3 trials and also internationally in more than 20 countries. And Stein is now expanding his scope to test whether progesterone can work its magic in other conditions, such as stroke, pediatric TBI, and brain tumors.

22 EMORY MEDICINE ww

“I’ve spent most of my professional clear it away and rebuild. That’s where For Stein, applying these positive career pursuing this line of work,” says progesterone shines. It’s a developmental findings to other conditions only makes Stein, Asa Candler Professor of Emer- hormone that is involved through the sense. “Everything we do has to do with gency Medicine and director of the de- entire gestation of the fetus. So here you brain injury,” he says. “Whether it’s from partment’s Brain Research Laboratory. have an agent that not only blocks all a head trauma, a stroke, or a tumor, it’s “Seeing our work in worldwide clinical these toxic events, but it also stimulates still an injury to the brain.” trial is exciting, but what would really regenerative repair.” In collaboration with the Pediatric be gratifying would be to know that the Progesterone certainly took a step Emergency Care Applied Research work we did actually ended up helping toward proving its worth in the small Network (PECARN) and the University a lot of people to live more healthy and 100-patient phase 2 trial. Stein and his of Michigan, his lab is looking into the fulfilling lives.” team were merely hoping to demon- effect of progesterone on youngerTBI A positive outcome from the trial strate that the high dose of the hormone victims. “There is currently very little could mean just that. Researchers have that can be done for children with severe tried unsuccessfully for decades to de- brain injuries—that’s a wide open field,” velop an acute treatment for TBI. says Stein. “But we need to make sure if “The graveyard for drugs and prom- we are working with a powerful develop- ising therapies for TBI is extensive,” says mental hormone it’s going to be as safe David Wright, associate professor in and effective in kids and not produce emergency medicine. “There have been any untoward effects. This work is still in many attempts, but zero have made it very preliminary stages.” past a phase 3 clinical trial in something Much further along is Stein’s re- that is epidemic in this country.” search using progesterone to treat stroke All those failures stemmed from victims. When rats were given proges- looking at the problem the wrong way, terone after having an induced stroke, contends Stein. “One of the main rea- they experienced about 70% less brain sons every single drug has failed is the damage than rats in the control group persistent approach to target one gene, and had 50% to 60% greater functional one pathway, one receptor, thinking you recovery. “We did gait scans to check the are going to find a magic bullet to treat a use of all limbs, a maze to test memory, a very, very complex disorder,” says Stein. grip analysis to test grip, and many other Indeed, with TBI the initial injury is functional assessments,” says Fahim Atif, just the beginning. Even a very localized a researcher in Stein’s lab. “In all areas, trauma results in a cascading release of For years Donald Stein persisted in the progesterone rats performed signifi- inflammatory factors that cause swelling, his research despite many naysayers, cantly better than the control rats.” tissue breakdown, and programmed cell who are now quiet. In the laboratory, researchers also death. “When you have a brain injury, are investigating the timing of proges- you have a systemic disease,” says Stein. terone administration, treating animals “Every organ in the body is affected. So if used was safe, so they could proceed to up to 24 hours after their stroke. “The you are just treating one spot in the brain a larger trial. Any evidence of efficacy only FDA-approved drug for stroke has a or one pathway, you’re going to fail.” would be gravy. They got gravy. very narrow window—it must be given Progesterone, on the other hand, “Much to our surprise, we saw a within 3-1/2 hours of the stroke,” says works at multiple genes, multiple 50% reduction in death in the treatment Atif. “As a result, less than 5% of the pathways, and multiple receptors. Not group, which was just over the top,” stroke population gets it. And even those only is it able to stem the devastating says Wright. “And in a certain sub- 5% are at risk for serious side effects, inflammatory cascade, it actually helps group, we also saw functional improve- such as brain hemorrhage. If progester- repair the damage. “If you tear down a ment. That shifted the whole curve one proved effective even after a 24-hour building, are you just going to leave the from keeping people alive to actually delay—as it has in animal models with rubble?” says Stein. “No, you’re going to making them better.” TBI—it could provide a much safer treat-

SPRING 2013 23 ment for many, many more people than ing on a project to develop a synthetic of brain tumors, such as glioblastoma is currently available.” version of progesterone that might be and astrocytoma.” Stein and his team of research more effective in treating brain injury Finally, Stein’s lab is working with scientists hope to wrap up the pre- than the native form of the hormone, the Department of Chemistry and the clinical work and move the stroke study Atif happened to use tumor cells in laboratory group of Dennis Liotta, the into human trials in the near future. his testing. As a part of the screening Samuel Candler Dobbs Professor of “Progesterone promises to have an even process, he found that high doses of Chemistry, to modify progesterone more profound influence on stroke than progesterone were toxic to the cells. “At to make it viable for use in the field, it has on TBI,” says Stein. first I was sure I did something wrong, particularly in combat situations. “In Stein’s lab is having even more suc- so I repeated a military situation, if you can help it, cess in improving outcomes in animal i t “Everything we about 10 you don’t want to have to start an IV models of trauma and stroke when do has to do with more times and keep it going,” says Stein. “You want progesterone is combined with vitamin and got the something that you can get in quickly brain injury, D. “Vitamin D is actually a hormone, same result and easily, that can be used in all condi- like progesterone, and it acts on many whether it’s from each time,” tions, from -40 degrees to 120 degrees, different biochemical pathways, like a head trauma, says Atif. that is highly stable so you don’t need progesterone,” says Stein. “We started a stroke, or a Subsequent to replace it every two weeks, and that working with vitamin D hormone at tumor, it’s still an research lasts in the system until you can get the the urging of Mahlon DeLong, the for- injury to the brain.” confirmed injured person to a hospital. And that’s mer chair of neurology here at Emory. his findings. what we’re trying to develop.” –Don Stein It turns out that both the very young Mice treated It’s hard to overstate the impact and the elderly often suffer from vita- with high- Stein’s work will have if the phase 3 min D deficiency and this can impair dose progesterone had a 50% reduction trial shows progesterone’s efficacy in the processes of healing after traumatic in neuroblastoma tumor size after only treating TBI. “Others have said if this brain injury or stroke. When used in eight days. The hormone induced cell works, it will dramatically change emer- combination, the two hormones work death and inhibited vascular growth. gency care and treatment of brain in- better than either does alone. In a “We published this work last year in the jury, and that it could become standard study we just published, there was sig- journal Molecular Medicine, and we are of care around the world,” says Stein. nificantly less brain damage and more very encouraged by the findings,” says “But the real beauty is that progesterone functional recovery in stroke-induced Atif. “Especially since every chemo- is really cheap, it’s easy to administer, rats that got progesterone and vitamin therapy drug has severe side effects and and it doesn’t require high technology. D in combination than in rats that got progesterone appears to have none. It So you can’t get away with charging vast progesterone or vitamin D alone.” specifically kills the cancer cells but is amounts of money for it, and there’s no Another area of research was stum- absolutely safe for healthy, normal cells. reason it couldn’t be available all over bled upon serendipitously. When work- We are now testing it with other types the world.” EM

Make the rounds Medical Alumni Weekend Save the Date: September 27-28, 2013

Don’t miss out on this great weekend!

24 EMORY MEDICINE

Postcard.indd 1 4/19/12 12:46 PM Class Notes alumni news

Oliver Thomas Guertsen to Wesley Donald to Clay Chap- Janet Witte 01M 02PH to Kelly Healy 00C 05M Leslie Choy-Hee 91Ox 93C pell 04M 11FM and Tresa John Hopkins 97M 01MR Chappell 98Ox 00C 04M

1980s 1990s cardiologist in Athens, Ga., Woodham recently joined and she is a pediatrician. Mercer University and the Gulshan Harjee 82M Scott Swygert 92M was Medical Center of Central 85MR received the 2012 named chief quality Kelly Healy 00C 05M Georgia in Macon, Ga., as Jack Raines Humanitarian officer and chief medical 06MR 10MR was named the director of maternal- Award from the Medical information officer for an assistant professor fetal medicine. Association of Georgia. Lakeland Regional of urology at Thomas She has conducted health Health Systems in Jefferson University in Shveta Shah 02C 07B 07M fairs for the uninsured for Lakeland, Fla. Philadelphia. and Dinesh Shah 00C the past seven years and 07G 07M have returned to established scholarship BORN: Oliver Thomas BORN: Rani Paige to Atlanta, and both are at the programs for high school Guertsen on April 24, 2012, Padmashree Chaudhury Gwinnett Clinic in Johns and college students. She is to Leslie Choy-Hee 91Ox Woodham 01C 05M Creek, Ga. Shveta is an president of First Medical 93C 97M 01MR and her 09MR and her husband, internist, and Dinesh is a Care in Decatur, Ga. husband, Kevin. She is Daron, on Oct. 23, 2012. neurologist. The couple has an obstetric hospitalist at two young children. Thomas Pearson 82M Wellstar Cobb Hospital. 88MR was appointed executive director of the 2000s A new prescription for diet Emory Transplant Center. Scott Isaacs 89C 93M He is surgical director of MARRIED: Janet Witte 98MR, of Atlanta, recently the kidney and pancreas 01M 02PH to John had his book, Beat Over- transplant program at Hopkins in February eating Now! Take Control of Your Hunger Hormones Emory Healthcare and 2011. She is a psychiatrist to Lose Weight Fast, the Livingston Professor in private practice and published by conducts depression of Surgery in the medical Fairwinds school. research at Massachusetts Press. He is the General Hospital. medical direc- Mark Furman 83C tor of Atlanta 87M 12B was named a BORN: Wesley Donald to Endocrine consultant at the Spencer Clay Chappell 04M 11FM Associates. Stuart executive search firm and Tresa Chappell 98Ox Scott Isaacs 89C 93M 98MR in Boston. 00C 04M on Nov. 9, 2012. He is an interventional

SPRING 2013 25 Class Notes alumni news

Padmashree Chaudhury Shveta Shah 02C 07B 07M Dinesh Shah 00C 07G 07M Lauren Hall 03C 08M 11MR Woodham 01C 05M 09MR

Lauren Hall 03C 08M Kerry Ressler (psychiatry) 1950s Prentis Huff 49Ox 50C 11MR is a Global Health was elected to the Institute 52G 55M 60MR, of Corps pediatrician in of Medicine. He is on the Duncan Farris 49C 51M Atlanta, on July 1, 2012. Swaziland with the Baylor medical faculty at Emory. 55MR, of Gainesville, He is survived by his wife, International Pediatric Ga., on Oct. 7, 2012. He Dorothy, two daughters, AIDS Initiative at Texas Richard Weil (pediatrics) practiced obstetrics and and five grandchildren. Children’s Hospital. was reappointed to the gynecology for 23 years Georgia Composite Medical in Waycross, Ga. He is Lawrence Brannon 53C Residency Notes Board by Gov. Nathan Deal. survived by his wife, 56M 57MR, of Atlanta, on He is chief of pediatrics at Rachel, three children, five Nov. 22, 2012. He practiced Piedmont Hospital. psychiatry for 45 years Naureen Adam grandchildren, and a great- and specialized in alcohol (anesthesiology) has granddaughter. Nanette Wenger and drug addiction. He is joined the Atlanta office of (cardiology) was survived by five children, Interventional Spine & Pain Ted Staton 50C 53M named a master of the 15 grandchildren, and five Management. 57MR, of Decatur, Ga., on American Association Sept. 17, 2012. He was a great-grandchildren. of Cardiovascular and Jennifer Cranny urological surgeon. Pulmonary Rehabilitation. Earle Toler 52C 56M, of (radiology) was named the She is on the medical East Point, Ga., on Aug. on-site medical director at Davis Boling 49C 54M faculty at Emory. 4, 2012. He is survived by East Cooper Medical Center 56MR, of Tampa, Fla., on his wife, Jackie, and two in Mount Pleasant, S.C. Aug. 5, 2012, of cancer. Deaths He met his wife of 57 children. Paul Fedalen (surgery- years, Marjorie, at Emory, Charles Finney 56C 59M cardiovascular) recently 1940s where she served as the 60MR 80B, of Albany, joined Bayhealth administrative assistant Ga., on Aug. 11, 2012. He Cardiovascular Surgical Herbert Arnold 43C 45M to the dean of the medical was an ophthalmologist Associates in Dover, Del. 49MR, of Tuscaloosa, school. They moved to before starting a pecan Ala., on Nov. 27, 2012. Tampa, where he was an farm. He also owned two Susan Jones (internal He was 90. He is survived orthopaedic surgeon for radio stations in Albany. medicine) has joined the by his wife of 66 years, 40 years. In addition to his He is survived by his wife, Memorial Medical Group, Nell, three children, five wife, he is also survived Charlie, four children, eight the largest physician group grandchildren, and two by five children and 12 grandchildren, and two in southwest Louisiana. great-grandchildren. grandchildren. great-grandchildren.

26 EMORY MEDICINE Deaths alumni news William Holloway (surgery), of Greenwood, S.C., on Sept. 11, 2012. He was 74. He was a vascular surgeon and opened the first accredited vascular center in South Carolina, the Carolina Vascular Institute at Self Regional Medical Center.

George Long (obstetrics Davis Boling 49C 54M 56MR William Weatherly 55C 59M Margaret Ann Gangarosa and gynecology), of 66MR 74C 82M 86MR Atlanta, on Nov. 15, 2012. Long had idolized Bernard Hochberg 59M, 1960s 1970s his father, a doctor who of Tampa, Fla., on Oct. 14, was the grand-nephew 2012. He was 77. He was Frank Pittman 60M Render Nesmith 68C 73M, of physician Crawford born in Sokolow, Poland, 61MR, of Atlanta, on Nov. of Inglewood, Calif., on W. Long, and had always and at the onset of WWII, 24, 2012, of cancer. He was Feb. 23, 2012. He was 65. said that he knew even his family fled to Russia. a psychiatrist in private as a small boy that he They were forcibly relocated practice, a clinic assistant 1980s would follow in his father’s to Siberia and then to professor at Emory, and a footsteps and become a Margaret Ann Gangarosa Uzbekistan. After the war, consultant at the Clayton doctor. Seven days after his 74C 82M 86MR, of they reunited with family in County Mental Health own father’s funeral service, Brookville, Fla., on Oct. 25, France and stayed in Paris Center. He is survived Long died of a suspected 2012, of metastatic renal for several years before by his wife, Elizabeth, heart attack. He was 56. cancer. She was 59 and had being allowed to immigrate three children, and seven He is survived by his wife, served as a pathologist for to the United States. They grandchildren. A prolific Debbie, and three children. 28 years. She was preceded arrived in 1949 aboard the writer, Pittman wrote in death by her husband, ocean liner Mauretania. frequently about marriage Isabel Ochsner (emergency John Pullin. She is survived Hochberg continued to and family relationships. medicine), of New Orleans, by her parents and three celebrate his personal on Nov. 6, 2012, of brothers. holiday, “Mauretania Day,” Martin Reeves 63M 69MR, pancreatic cancer. She was each year. In 1970 he joined of Suwanee, Ga., on June Residency 56. She is survived by three St. Joseph’s Hospital as a 22, 2012. He was 73. He is sisters. urologist. He is survived by survived by his daughter Deaths his wife, Moira, four sons, and three grandchildren. Mason Robertson (internal and five grandchildren. John Gilligan medicine), of Augusta, Frank Schuler 68M (ophthalmology) of Ga., on July 20, 2012. He William Weatherly 55C 73MR, of Newport News, Alexandria, Va., on April moved to Savannah, Ga., 59M 66MR, of Atlanta, on Va., on Oct. 6, 2012. He 10, 2012. He was preceded in 1958 and practiced there Aug. 5, 2012. He was 79. He practiced plastic surgery in death by his wife, for 25 years. He and his was a psychiatrist for more for more than 40 years. Barbara, and his oldest wife, Mary, were active in than 40 years before retiring He is survived by his wife, son, John, and is survived desegregation efforts in in 2009. He served as a Sandra, four children, and by four children and six Savannah, participating clinical professor at Emory. two grandchildren. grandchildren. in lunch counter sit-ins. He is survived by his wife, His medical practice also Jody, and four children. was desegregated at a

SPRING 2013 27 Deaths alumni news Warren Sarrell by his wife, Alice, and two (cardiology) of Anniston, children. Ala., on Sept. 27, 2012, of bone marrow Faculty Deaths cancer. He was 87. He was instrumental in Hugh Randall 69Ox 71C establishing the Sarrell 75M 79MR, of Crossville, Dental Clinic, which now Tenn., on July 1, 2012. has 14 facilities across He was 63. He joined Alabama and is the main the Emory gynecology/ provider of dental care obstetrics faculty in 1979 for children on Medicaid. and served at Grady. He Mason Robertson Warren Sarrell He is survived by his wife, also served on the faculties Lela, six children, and 14 of New York University and time when many were not. the W. W. Law Award from grandchildren. Lincoln Memorial-DeBusk In 1987 he received the the Economic Opportunity College of Osteopathic NAACP Freedom Award. Authority of Savannah for Stanley Shapiro (surgery- Medicine. He is survived by He also helped establish the their civil rights efforts. otolaryngology), of Sandy his wife, Sandra, and two first sickle cell anemia clinic He was preceded in death Springs, Ga., on Nov. 18, daughters. in Savannah. He retired in by his wife, Mary, and is 2012. He practiced at 1984 due to the effects of survived by three children Wellstar Cobb Hospital and Parkinson’s disease. In 2008, and five grandchildren. Wellstar Douglas Hospital he and his late wife received for 40 years. He is survived

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28 EMORY MEDICINE Kamal Mansour 68MR began his career in 1966 as chief resident in cardiothoracic surgery at Emory University Hospital. An international pioneer of lifesaving techniques, he has shared his passion for medicine with thousands of students, faculty members, and patients for 47 years now. His residents dubbed him “the Tasmanian devil” for his speed in surgery and Plan to “the professor” for his devotion to teaching. Now Mansour is making an say thank endless contribution to thoracic surgery at Emory: He and his wife, Cleo, have established the Kamal A. Mansour Professorship through a provision you. in their wills.

Find out more about gift planning. Visit www.emory.edu/giftplanning or call 404.727.8875. WINTER 2011 29 Emory University Alumni Records Office 1762 Clifton Road Atlanta, Georgia 30322

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1st Row (l-r): Kalpana Rengarajan, Emory University; Dave Williams, Georgia Tech; Wendy Wright, Emory University, Emory Healthcare and Children’s Healthcare of Atlanta; Jo-Ann House, Emory Transplant Center; Shaneesa Ashford, Emory University; Gukseop Yun; Yael Levy, The Times of Israel; L’Bertrice Hopson, P.E.N. Television Inc.; Thanicia Childs, Emory University. 2nd Row: Tye Tavaras; Cindy Mayz, Emory University; Amy Mansfield, Kilpatrick Townsend; Paula Scotman, Emory University; Tarik Johnson; Pam Terry, Emory University; Cyndi Romero, Enercon Services. TopResearchers Row: John Kosky, and Emory clinicians University; Octavian trying Blaga, Tenet; Ed Moseley, Emory University; Mariam Iobidze; John Holmes; Patricia Olinger, Emory University; Steve Nelson; and Adrianne Grubic, CNN. to bring a product to market find the challenging world of venture Law School: capital a little easier to navigate It isn’t just for lawyers anymore. after taking a FastTrac course. 20 30 EMORY MEDICINE Learn more at www.law.emory.edu/jm