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The newspaper of The Johns Hopkins University April 17, 2006 | Vol. 35 No. 30
SoM Honors 17 Young Researchers

Crista Brawley, winner of the Martin and Carol Macht Research Award, with adviser Erika Matunis of Cell Biology.

Young Investigators' Day recognizes 'the once and future stars at Hopkins'

By Audrey Huang
Johns Hopkins Medicine

Alongside every successful professor is an army of hard-working, dedicated and talented students and fellows.

On Thursday, April 20, the School of Medicine will recognize 11 students and six fellows for their exceptional research accomplishments during the 29th annual Young Investigators' Day celebration, a Hopkins tradition.

The 17 investigators were chosen from a pool of nearly 100 outstanding applicants, according to the chair of this year's faculty committee, Randall Reed, a professor of molecular biology and genetics in the Hopkins Institute for Basic Biomedical Sciences. "It was really hard to come to the final decisions," he says. "These are the once and future stars at Hopkins."

The research projects recognized this year range from the molecular genetics of visual transduction in Drosophila to studies of how a schizophrenia-associated mutation disrupts cerebral cortex development. The awards are named after former Johns Hopkins students and well-respected former faculty members. They are accompanied by a cash prize, funded by friends, family and the Johns Hopkins Medical and Surgical Society.

"The Young Investigators' Awards are really about recognition as much as competition," Reed says. "We try to recognize those who have done particularly excellent work and made unique and individual contributions to the research."

The program will start at 4 p.m. in Mountcastle Auditorium, where selected awardees will present their research and all will receive honors. A poster session and reception will follow.

"I've always dreamed about being a part of this ceremony," says neuroscience fellow Sangwon Kim, recipient of the A. McGehee Harvey Research Award, who discovered a connection between two different molecular pathways involved in inflammation while working in the lab of Solomon H. Snyder, Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry in the Department of Neuroscience that bears his name.

Jason Shepherd, a doctoral candidate in the Cellular and Molecular Medicine program, is one of the four recipients of the Paul Ehrlich Award. "The scope and breadth of the science here at Hopkins is truly mind-boggling," he says.

Working jointly with professors of neuroscience Paul Worley and Richard Huganir, Shepherd linked a protein called Arc to the control of signaling at nerve endings and showed this relationship to play a role in learning and memory. Using a mouse model, Shepherd removed Arc and found the mice to have only selective memory.

Another recipient of the Ehrlich Award, M.D. candidate Brad Barnett, worked with adviser Aravind Arepally to encapsulate insulin-producing human islet cells and transplant the capsules into pigs, with sights on improving a treatment for type 1 diabetes. The existing method of islet transplantation calls for delivering invisible cells through a needle guided by ultrasound into the portal vein, which connects to the liver. By putting islet cells into capsules, Barnett has developed a method that allows doctors to follow the capsules by MRI, so they can make sure the islet cells end up in the right place; additionally, Barnett's approach introduces the cells through the femoral vein in the leg, which is more accessible and easier to steer through than the portal vein.

Barnett says that he shares with his award's namesake an attitude toward research. "As [Ehrlich] once said, 'The first rule of intelligent tinkering is to save all the parts.' And given the complexity of this universe and the limits of our senses, we would be foolish to think we are capable of anything more than intelligent tinkering."

Jordan Steinberg, an M.D./Ph.D. candidate in neuroscience, says that he also feels a special connection to the namesake of the award that he received: the Nupur Dinesh Thekdi Award, which honors a former M.D./Ph.D. student. "I was in my second year of the program when Nupur died in a tragic accident," Steinberg says. "He was a very accomplished student and scientist, and I am honored to receive the award in his name. I thank his family for having endowed the award so that others can continue in his path."

Steinberg's research led to the discovery of how a protein called PICK1 can control neuron function in a type of motor learning called the vestibulo-ocular reflex. By generating a collection of mouse mutants, Steinberg and his adviser, Richard Huganir, were able to definitively show how PICK1 controls receptors on the surface of Purkinje neurons.

The recipient of the Michael A. Shanoff Award was Meenakshi Rao, an M.D./Ph.D. candidate in neuroscience. "From day one," he says, "my adviser, Shan Sockanathan, gave me free reign to pursue my ideas, although many of them led nowhere."

Some of them did. Rao discovered a protein called GDE2 that is controlled by retinoic acid, a metabolite of vitamin A. GDE2 appears necessary for motor neuron differentiation in the spine and is a pioneer member of a new class of proteins that may be involved in a new type of signaling pathway.

Ph.D. candidate Daniel Bendor, seated, will be recognized with the David Israel Macht Research Award for his work with sponsor Xiaoqin Wang.

Daniel Bendor, a doctoral candidate in the Biomedical Engineering program, received the David I. Macht Research Award for his work, which was published in Nature. With mentor Xiaoqin Wang, Bendor did what others were unable to do previously: map the region of the brain in monkeys involved in hearing the pitch of a sound.

The pitch of a sound corresponds to its vibration. When you pluck a string, the whole thing vibrates. But it also vibrates in halves, quarters and smaller intervals. Each of these smaller intervals corresponds to a harmonic. Pitch neurons respond to multiharmonic sounds but not when any of the harmonics are played alone.

"We seem to have found the same region of the brain that humans use for pitch perception," says Bendor, a fifth-year student who anticipates graduating next year. In humans, pitch is important for understanding speech and appreciating music. Animals use pitch to identify and discriminate vocalizations, for communication.

Bendor took electrical readings of single neurons in the brain to map out which cells are responsible for hearing pitch. Those neurons are active only when certain sounds are played. By comparing the electrical behaviors of different neurons in response to different sounds, Bendor was able to pick out the pitch-responsive neurons.

A musician and composer in his spare time, Bendor says, "This award is a great honor, and I'm also fortunate in that my research overlapped with my hobby."

Crista Brawley, a doctoral candidate in the Cellular and Molecular Medicine program, received the Martin and Carol Macht Award for her project, "Stem Cell Niche Repopulation in Vivo Via Dedifferentiation."

Although it is well accepted that stem cells can repopulate injured tissue, where those stem cells come from and how repopulation is controlled is not well understood. One idea that had never been proved was that of dedifferentiation, where cells that have taken on a certain identity like muscle or skin somehow lose that identity and revert to a stem cell state.

Brawley, in her work, was able to manipulate a signaling pathway in specific cells of Drosophila to coax them into reverting into stem cells.

"The word dedifferentiation was the scary part," says Brawley, whose work was published in Science. "Most stem cell biologists avoid this word because it is so hard to prove."

The sperm of fruit flies develop from a population of stem cells called germline stem cells. Every time one such stem cell divides, one daughter cell becomes a future sperm, while the other stays behind as a germline stem cell to maintain the stem cell population so that more sperm can be made. Fruit flies mutant for a gene called STAT, however, are unable to maintain a population of germline stem cells; when the germline stem cells in STAT mutant flies divide, both daughter cells become sperm, leaving no stem cells behind. When Brawley reintroduced STAT back into the mutant flies, she noticed the reappearance of germline stem cells. But her adviser, Erika Matunis, was skeptical.

"It took some convincing, as Erika didn't believe me at first," Brawley says. "I repeated those initial experiments many times."

But when Brawley streamlined her experimental approach and showed, by adding STAT, that the developing sperm could indeed revert to a stem cell state, Matunis was sold. "She was stunned," Brawley says. "But I trusted my gut that I had something novel; I only had to convince my adviser of the same.

"This [recognition] is a reward for all the hard work and long days and years I've put into work at Hopkins," Brawley says. "The award solidifies for me that I have made the correct choice in choosing a career in science."

Postdoctoral fellow Ronald Cohn, right, will receive the Helen B. Taussig Research Award honoring the project he conducted with sponsor Harry 'Hal' Dietz.

Ronald Cohn, a postdoctoral fellow in the McKusick-Nathans Institute of Genetic Medicine, received the Helen B. Taussig Award for his project, "TGF Beta-Induced Failure of Muscle Regeneration in Multiple Myopathic States." Cohn, with adviser Hal Dietz, found that a too-high level of the growth factor TGF-beta leads to an inability to repair muscle in mouse models for two diseases, Marfan syndrome and Duchenne muscular dystrophy. Marfan syndrome is a connective tissue disorder associated with aortic aneurisms and skeletal abnormalities. Duchenne muscular dystrophy is the most common inherited form of muscular dystrophies in children.

Skeletal muscle has the unique ability to repair itself after injury through regeneration; if muscle regeneration doesn't happen, muscle mass and strength are lost.

"We can prevent failed muscle regeneration in mouse models for both diseases by blocking TGF-beta signaling with a known drug," Cohn says.

By looking at genes known to be turned on by TGF-beta signaling, Cohn showed first that TGF-beta signaling is indeed the cause of muscle loss in animals with Marfan, as well as in animals with Duchenne muscular dystrophy. By blocking TGF-beta signaling, Cohn showed that muscle loss could be prevented in those same animals.

"I feel deeply honored to have been chosen to receive the Helen B. Taussig Award among so many excellent young scientists here at Hopkins," Cohn says, noting that Taussig made many groundbreaking contributions to medicine within the field of pediatric cardiology and also by supporting a wide range of social causes, including her successful campaign in the 1960s to ban the use of thalidomide by pregnant women. "I have a special interest in compassionate care," Cohn says, "and I hope the karma associated with her accomplishments will positively impact my future career as a physician/scientist."


2006 Young Investigators' Day

Thursday, April 20, Mountcastle Auditorium of the Preclinical Teaching Building on the East Baltimore campus
4 p.m. Welcome from Edward D. Miller, dean of the medical faculty and CEO of Johns Hopkins Medicine, and student lectures
4:05 p.m. The Michael A. Shanoff Research Award
"Transmembrane protein GDE2 directs spinal motor neuron differentiation in vivo"
Meenakshi Rao, M.D./Ph.D. candidate, Neuroscience Graduate Program
Sponsor: Shanthini Sockanathan, assistant professor, Neuroscience

The David Israel Macht Research Award
"The neuronal representation of pitch in primate auditory cortex"
Daniel Bendor, Ph.D. candidate, Biomedical Engineering Graduate Program
Sponsor: Xiaoqin Wang, professor, Biomedical Engineering

The Martin and Carol Macht Research Award
"Stem cell niche repopulation in vivo via dedifferentiation"
Crista Brawley, Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program
Sponsor: Erika Matunis, assistant professor, Cell Biology

The Paul Ehrlich Research Award
"Arc regulates synaptic scaling of AMPA receptor"
Jason Shepherd, Ph.D. candidate, Cellular and Molecular Medicine Graduate Program
Sponsors: Paul Worley and Richard Huganir, professors, Neuroscience


The Paul Ehrlich Research Awards
"Identification of a novel hedgehog receptor from a systematic survey of the Drosophila genome"
Shenqin Yao, Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program
Sponsor: Philip Beachy, professor, Molecular Biology and Genetics

"Molecular genetics of Drosophila visual transduction" Tao Wang, Ph.D. candidate, Biological Chemistry Graduate Program
Sponsor: Craig Montell, professor, Biological Chemistry

"MR-guided transplantation of magneto-capsules immunoprotecting pancreatic islets"
Brad P. Barnett, M.D. candidate
Sponsor: Aravind Arepally, assistant professor, Radiology

The Hans Joaquim Prochaska Research Award
"Chemical rescue of a mutant enzyme in living cells"
Yingfeng Qiao, Ph.D. candidate, Pharmacol-ogy and Molecular Sciences Graduate Program
Sponsor: Philip A. Cole, director, Pharmacology and Molecular Sciences

The Mette Strand Research Award
"Parietal eye phototransduction components: Insight into vertebrate photoreceptor evolution"
Chih-Ying Su, Ph.D. candidate, Neuroscience Graduate Program
Sponsor: King-Wai Yau, professor, Neuroscience

The Alicia Showalter Reynolds Research Award
"Catalysis in translation elongation and termination"
Elaine M. Youngman, Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program
Sponsor: Rachel Green, associate professor, Molecular Biology and Genetics

The Nupur Dinesh Thekdi Research Award
"Cellular and molecular mechanisms of long-term synaptic depression in the cerebellum"
Jordan Philip Steinberg, M.D./Ph.D. candidate, Neuroscience Graduate Program
Sponsor: Richard Huganir, professor, neuroscience


The Helen B. Taussig Research Award
"TGF-beta-induced failure of muscle regeneration in multiple myopathic states"
Ronald D. Cohn, postdoctoral fellow, McKusick-Nathans Institute of Genetic Medicine
Sponsor: Harry C. Dietz, professor, Pediatrics, and HHMI associate investigator, Institute of Genetic Medicine

The A. McGehee Harvey Research Award
"Synergistic inflammatory mechanisms with therapeutic relevance"
Sangwon Kim, postdoctoral fellow, Neuroscience
Sponsor: Solomon Snyder, professor, Neuroscience


The W. Barry Wood Jr. Research Award
"Schizophrenia-associated DISC1 mutation perturbs cerebral cortex development"
Atsushi Kamiya, M.D., postdoctoral fellow, Psychiatry and Behavioral Sciences
Sponsor: Akira Sawa, assistant professor, Psychiatry

The Daniel Nathans Research Award
"hAT element transposition"
Liqin Zhou, Ph.D., postdoctoral fellow, Molecular Biology and Genetics
Sponsor: Nancy L. Craig, professor, Molecular Biology and Genetics

The Alfred Blalock Research Award
"Genetic and functional analysis of the PIK3CA oncogene in human cancers"
Yardena Samuels, Ph.D., postdoctoral fellow, Oncology-Cancer Biology
Sponsor: Victor Velculescu, assistant professor, Oncology-Cancer Biology

The Albert Lehninger Research Award
"Genetic selection of forward transport signals directing cell surface expression"
Sojin Shikano, Ph.D., postdoctoral fellow, Neuroscience
Sponsor: Min Li, professor, Neuroscience



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