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The newspaper of The Johns Hopkins University April 11, 2005 | Vol. 34 No. 29
SOM Honors Young Researchers

Alicia Showalter Reynolds Research Award recipient Luisa Cochella, right, in the laboratory with mentor Rachel Green.

Young Investigators' Day recognizes innovative, groundbreaking work

By Joanna Downer
Johns Hopkins Medicine

It's said that "two's company, three's a crowd." But in scientific research, the right cliche more often is "the more, the merrier."

At the School of Medicine on April 14, 11 students and seven fellows will join the ranks of Young Investigators' Day award recipients during the 28th annual celebration of trainees and their work. The awardees, representative of their peers, will present their work and receive their awards starting at 4 p.m. in Mountcastle Auditorium.

"It's important to have an opportunity for the faculty and administration to formally step back and acknowledge how lucky we are to have such excellent students and fellows," says Jon Lorsch, assistant professor of biophysics and biophysical chemistry. "A few students have been selected for the actual awards, but they should be viewed as figureheads for all the fantastic students at Hopkins."

Many of this year's awardees have succeeded by seeking out people who can fill gaps in their knowledge, help interpret their findings or provide a new way of looking at problems. Students, fellows and faculty alike say that this collaborative atmosphere is a key component of research success across the institution.

For example, Shin Lin, a graduate student in the Human Genetics Program and recipient of one of this year's four Paul Ehrlich Awards, recognized a gap in his training and sought biostatistics help from experts at the Bloomberg School of Public Health. The classroom training and one-on-one guidance he received provided the foundation he needed, he says.

"When I first arrived on campus, I wanted to participate in the commotion the Human Genome Project was generating," he says. "I wanted to know how it could be used and what new inquiries could be made."

This interest in using the human genome sequence or the subsequent "HapMap" project, which is identifying DNA inherited as intact chunks, to understand the genetics of complex common diseases such as autism or diabetes had a potentially bigger problem, however. Some scientists in the field thought it would be impossible to get meaningful information from the data.

But Lin and mentor David Cutler, a professor in the McKusick-Nathans Institute of Genetic Medicine, have proved the naysayers wrong. They figured out how to accomplish powerful genomewide association studies while incorporating a critical analysis used in very focused genetic studies, and to do so in real time with meaningful results.

"We drew on concepts rooted in population genetics and statistics and coded them in an elegant computer algorithm," says Lin, who added a master of health sciences along the way.

Already, Lin's system has been used to help identity a risk-increasing gene behind Hirschsprung disease, and it will be applied to the hunt for genes contributing to autism, efforts of other investigators at Johns Hopkins.

Such collaboration is a natural at Johns Hopkins, it seems.

"We have a great interaction with Jon Lorsch's lab, even though we don't have a formal collaboration," says Rachel Green, professor of molecular biology and genetics. "We have an overlap in technology and approach that really helps what we do."

Sponsor Jon Lorsch with David Maag Jr., who received this year's Mette Strand Research Award. Maag will also be one of the student lecturers at Thursday's event.

Lorsch's lab and Green's lab study biology's protein-building machinery, the ribosome, and both labs have an awardee this year. One of Lorsch's graduate students, David Maag Jr., will receive the Mette Strand Research Award for figuring out how the yeast's ribosome recognizes the right place to start reading RNA. Lorsch and Maag's work was published in January in Molecular Cell.

Similarly, one of Green's graduate students, Luisa Cochella, will receive this year's Alicia Showalter Reynolds Research Award for her work showing that so-called transfer RNA, or tRNA, actively participates in turning on the ribosome. Green and Cochella's paper has just been accepted by Science.

"Luisa came up with the idea on her own after other projects didn't work out," Green says. "None of the systems existed to study the question, so she had to develop them and really had to persevere. There's a culture in the lab, and at Hopkins in general, that science is fun and exciting and that hard work pays off. That's really important for success."

Hard work, creativity, a supportive environment, brilliant colleagues, great mentors — a little luck — are all cited by the awardees as contributing to their projects' successful conclusions. But this year, more awardees seemed to mention how much others' expertise was needed to get robust research results, possibly reflecting the widespread anticipation that future scientific research will be multidisciplinary.

Sometimes the extra expertise came from outside the "home" lab. Lin went across the street, and Maag went across town for the expertise of Lorsch's collaborator Zygmunt Gryczynski at the Center for Fluorescence Spectroscopy at the University of Maryland Medical School. WenYong Chen, a postdoctoral fellow in oncology and recipient of this year's A. McGehee Harvey Research Award, relied on the expertise of pathologist Joseph Mankowski in comparative medicine.

But for graduate student Vikas Bhandawat, recipient of a Paul Ehrlich Research Award, and for other awardees, the extra expertise was at the next bench — figuratively and literally. Bhandawat joined King-Wai Yau's neuroscience lab at the same time Johannes Reisert joined as a postdoctoral fellow. In his previous position at Cambridge, Reisert had helped develop techniques to deliver precise concentrations of odor molecules to nerve cells in culture and to do so for precise periods of time.

"People had been recording from odor-detecting nerves for the last 15 years, but they had been using a fairly unstable whole-cell recording technique [to detect and measure the cell's reaction], and they had not used very defined pulses of odorants," says Bhandawat, whose work used Reisert's techniques to show that odor-detecting receptors use a common signaling pathway, G-protein signaling, in a previously unknown way. "Simply using a more quantitative approach can sometimes open up avenues that would otherwise remain unexplored."

Bhandawat's work and the research of other Johns Hopkins trainees and award recipients often challenge or overturn scientific dogma and paradigms long accepted although not proven. Many times the awardees' work is published by a major journal, a scientific "stamp of approval," but neither the journals nor the award committee can catch everything.

"To me what really marks research success is the creative or innovative process," says Jef Boeke, mentor to graduate student Jeffrey Han, this year's Michael A. Shanoff Research Award recipient. "Often this kind of research takes place ahead of its time and/or in an unusual context so far outside the mainstream that it is not recognized by awards, etc. But these are the really enduring breakthroughs."

Bhandawat feels the Young Investigators' Day awards have done a pretty good job of catching the biggies, though.

Jeffrey Han, recipient of this year's Michael A. Shanoff Research Award, with sponsor Jef Boeke. Han will lecture on his work at the awards ceremony.

"I'm always struck by the originality of the research presented at Young Investigators' Day," he says. "Not all great ideas are immediately accepted by the scientific community, and therefore not all make it to the high-profile journals. I think the awards committees over the years have done a great job of representing such ideas."

This year's oral presentations will cover a wide range of research, from the effect of low pH on gene activity, to how developing nerves are guided, to HIV's behavior, to predicting whether early stage prostate cancer might eventually be deadly. The day provides a great opportunity to hear about a variety of other people's work and to shed the weight of the lab, if only for a short time.

"Life as a graduate student is mostly filled with failed experiments and very little positive feedback, so it's rewarding to have your work recognized," says Han, the Shanoff awardee for his research on the effects of retrotransposons, or "jumping genes," on gene function and evolution. "That being said, I think one point of Young Investigators' Day should be to celebrate the contributions and sacrifices that all graduate students make for their research."

Chris Brett, recipient of this year's David Israel Macht Research Award, echoes that sentiment. "I'm familiar with the work of many fellow students and can honestly say that I am a typical example, not an exception, of the quality of young scientists Hopkins is producing."

Of course graduate students aren't the only ones keeping the wheels of research churning. Seven postdoctoral fellows receiving Young Investigators' Day awards represent the important contributions of their cohorts in laboratory and clinical settings at the medical school.

Many of the awards are named for prominent Johns Hopkins scientists, such as Helen Taussig, W. Barry Wood and Daniel Nathans, and for former students and alumni, such as Michael Shanoff, Nupur Dinesh Thekdi and Alicia Showalter Reynolds, who left gaps in the Johns Hopkins community and in biomedical science when they died. Funding of the awards comes from friends and family and the Johns Hopkins Medical and Surgical Society.

When possible, the awards committee — composed of faculty members and headed for the third year by Se-Jin Lee, professor of molecular biology and genetics — tries to match the legacy of an award's namesake to the applicant's research.

For example, surgeon Stephen Freedland, who identified characteristics of early-stage prostate cancers that can distinguish patients at high risk or low risk of death from recurrence, will receive the award named after famed Johns Hopkins surgeon Alfred Blalock.

Similarly, Rejji Kuruvilla, one of two postdoctoral awardees from the Howard Hughes laboratory of neuroscientist David Ginty, feels particularly rewarded by being named the Helen Taussig Research Award recipient. "As a woman scientist, it is satisfying for me to receive an award in honor of one of the most renowned women physicians at Hopkins and in this country," says Kuruvilla, now an assistant professor of biology in the Krieger School of Arts and Sciences.

"Young Investigators' Day is a great opportunity to reward and recognize the hard work of students and fellows," adds neuroscience postdoctoral fellow Damian van Rossum, who is sharing this year's Albert Lehninger Research Award with biological chemistry postdoctoral fellow Natasha Zachara. "The event also brings together researchers from a broad spectrum of disciplines, manifesting a feeling of community and a forum for the exchange of ideas."

Right. The more, the merrier.


18 Researchers To Be Honored for Their Contributions

2005 Young Investigators' Day
Thursday, April 14, 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

The Michael A. Shanoff Research Award
"L1 retrotransposons — Massaging and manipulating mammalian genomes"
Jeffrey S. Han, M.D./Ph.D. candidate, Biochemistry, Cellular and Molecular
Biology Graduate Program, Department of Molecular Biology and Genetics
Sponsor: Jef Boeke, professor, Molecular Biology and Genetics

The David Israel Macht Research Award
"pHome, Na+/H+ exchange and vesicle trafficking"
Christopher L. Brett, Ph.D. candidate, Cellular and Molecular Medicine Graduate Program, Department of Physiology
Sponsors: Rajini Rao, professor, Department of Physiology, and Mark Donowitz, professor of gastroenterology, Department of Medicine

The Mette Strand Research Award
"The mechanism of start site selection during eukaryotic protein synthesis"
David Maag Jr., Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program, Department of Biophysics and Biophysical Chemistry
Sponsor: Jon Lorsch, assistant professor, Biophysics and Biophysical Chemistry

The Hans Joaquim Prochaska Research Award
"Mechanism of HIV-1 latency"
Kara G. Lassen, Ph.D. candidate, Graduate Immunology Program, Department of Medicine
Sponsor: Robert F. Siliciano, professor, Department of Medicine


The Martin and Carol Macht Research Award
"The axon guidance cue Semaphorin 5A is functionally regulated by sulfated proteoglycans: Implications for development and regeneration"
David B. Kantor, M.D./Ph.D. candidate, Graduate Program in Neuroscience, Department of Neuroscience
Sponsor: Alex L. Kolodkin, professor, Neuroscience

The Nupur Dinesh Thekdi Research Award
"Nutrient control of gluconeogenesis through PGC-1a/SIRT1 deacetylase complex"
Joseph T. Rodgers, Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program, Department of Cell Biology
Sponsor: Pere Puigserver, assistant professor, Department of Cell Biology

The Alicia Showalter Reynolds Research Award
"Active role for tRNA in signaling its own acceptance into the ribosome"
Luisa Cochella, Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program, Department of Molecular Biology and Genetics
Sponsor: Rachel Green, associate professor, Molecular Biology and Genetics

The Paul Ehrlich Research Awards
"Elementary response of olfactory receptor neurons to odorants"
Vikas Bhandawat, Ph.D. candidate, Neuroscience Graduate Program, Department of Neuroscience
Sponsor: King-Wai Yau, professor, Neuroscience

"Glutamate uptake at excitatory synapses by astroglial transporters"
Yanhua H. Huang, Ph.D. candidate, Neuroscience Graduate Program, Department of Neuroscience
Sponsor: Dwight E. Bergles, assistant professor, Neuroscience

"EATDT: A novel algorithm for genomewide disease mapping"
Shin Lin, M.D./Ph.D. candidate, Predoctoral Training Program in Human Genetics and Molecular Biology, McKusick-Nathans Institute of Genetic Medicine
Sponsors: Aravinda Chakravarti, professor and director, Institute of Genetic Medicine; and David J. Cutler, assistant professor, Institute of Genetic Medicine

"Validating imaging results using acute stroke patients"
Lisa Philipose, M.D. candidate
Sponsor: Argye Hillis, associate professor, Neurology


The W. Barry Wood Jr. Research Award
"Molecular mechanisms of axon and vascular guidance"
Chenghua Gu, Ph.D., postdoctoral fellow, Department of Neuroscience
Sponsor: David Ginty, professor, Neuroscience

The Daniel Nathans Research Award
"Roles for Hedgehog signaling in cancer — Of brains, gut(s) and stem cells"
Sunil S. Karhadkar, M.D., postdoctoral fellow, Department of Molecular Biology and Genetics
Sponsor: Philip A. Beachy, professor, Molecular Biology and Genetics


The Helen B. Taussig Research Award
"Local and retrograde signaling by target-derived neurotrophins in neuronal development"
Rejji Kuruvilla, Ph.D., postdoctoral fellow, Department of Neuroscience
Sponsor: David Ginty, professor, Neuroscience

The Alfred Blalock Research Award
"Predicting prostate cancer specific mortality following biochemical recurrence after radical prostatectomy"
Stephen J. Freedland, M.D., postdoctoral fellow, Department of Urology
Sponsor: Alan W. Partin, professor and director, Urology

The A. McGehee Harvey Research Award
"Molecular mechanisms of HIC1 in tumor suppression"
WenYong Chen, Ph.D., postdoctoral fellow, Tumor Biology Laboratory, Sidney Kimmel Comprehensive Cancer Center
Sponsor: Stephen B. Baylin, professor, Oncology

The Albert Lehninger Research Award (shared)
"Phospholipase C-g1 controls surface expression of TRPC3 via an intermolecular PH domain"
Damian B. van Rossum, Ph.D., postdoctoral fellow, Department of Neuroscience
Sponsor: Solomon H. Snyder, Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry

The Albert Lehninger Research Award (shared)
"Increased glycosylation in response to stress, a survival mechanism of cells"
Natasha E. Zachara, Ph.D., postdoctoral fellow, Department of Biological Chemistry
Sponsor: Gerald W. Hart, professor and director, Biological Chemistry



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