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The newspaper of The Johns Hopkins University April 5, 2004 | Vol. 33 No. 29
SOM Honors Young Researchers

Daniel Southworth, recipient of a Paul Ehrlich Research Award, in the laboratory with mentor Rachel Green.

Young Investigators' Day recognizes innovative, groundbreaking work

By Joanna Downer
Johns Hopkins Medicine

For students, residents and postdoctoral fellows at Johns Hopkins, conducting research is an opportunity to learn — not just things they don't know, but things the world doesn't know.

On April 8, the School of Medicine will once again recognize the outstanding and important contributions of its graduate and medical students, postdoctoral fellows and clinical residents, who over the last year have answered scientific questions that have lingered for decades and even centuries.

The 27th Annual Young Investigators' Day celebration will begin at 4 p.m. in Mountcastle Auditorium in the Pre-Clinical Teaching Building, East Baltimore.

As part of the celebration, 10 doctoral candidates and six fellows and residents will receive Young Investigators' Day Awards and present their winning research (see below). Afterward, a reception will honor all of the institution's young investigators.

"This gives all of us at Hopkins a chance to celebrate what we have here — a large number of outstanding mentors, hard-working trainees who place a lot of importance on the quality of their research, and great interactions," says Sarah White, a Ph.D. candidate in the Cellular and Molecular Medicine graduate program who will receive this year's Martin and Carol Macht Award.

Recipients of Young Investigators' Day awards exhibit unusually independent thought and creativity in pursuing their research, frequently taking on projects their own mentors think may be too ambitious for the typical five-year graduate student stint or two- to four-year postdoc position.

For example, immunology graduate student Hao Jiang had to develop a complex, cell-free experimental system before he could tackle the real question at hand — how the immune system learns to recognize such a wide variety of "invaders." For previous students and postdocs, the details had been unreachable.

With the system he developed, however, Jiang uncovered the first link between the cell cycle (the steps cells go through in order to divide in two) and two mechanisms cells use to create and repair breaks in their genetic material. The discovery, for which Jiang will receive this year's David I. Macht Award, explains why recombination of DNA — a key step in creating the immune system's versatility — only happens at certain times in the cell.

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

But the awards, matched to recipients by a faculty committee which for the second year was headed by Se-Jin Lee, aren't just about honoring or memorializing people close to Hopkins. A. McGehee Harvey awardee Khurram Nasir and Paul Ehrlich awardee Gyanu Lamichhane, as well as other recipients, say they get a confidence boost and validation from the recognition, and the entire celebration helps encourage all students and postdocs to continue the legacy of the awards' namesakes.

Rowena McBeath, an M.D./Ph.D. candidate and recipient of the Nupur Dinesh Thekdi Research Award, with mentor Christopher Chen.

"Young Investigators' Day encourages those whose research careers are just beginning to bloom," says Rowena McBeath, an M.D./Ph.D. candidate in Cellular and Molecular Medicine and recipient of the Nupur Dinesh Thekdi Award for her work measuring how altering a primitive stem cell's "personal space" — letting it stretch out or keeping it bunched up — can affect its behavior. "The celebration emphasizes the importance of independent thinking, keen observation, perseverance and hard work as keys to research success at all levels of training."

The awards also give family members the chance to celebrate with young researchers without needing to understand the intricacies of the cell cycle, the complexities of neuroscience or the genetic goings-on of the tiny worm C. elegans.

"Everyone can appreciate the value of clinical studies, but the importance of basic research can be tough to explain to friends and family," says Jason Pellettieri, a Ph.D. candidate working with Geraldine Seydoux and recipient of this year's Hans Prochaska Award. "The award is a nice validation of my efforts in that respect. In fact, I think my grandmother was just as excited about the award as I was!"

Jason Pellettieri, recipient of this year's Hans Prochaska Award, with mentor Geraldine Seydoux. Pellettieri will lecture on his work at the awards ceremony.

All the awardees are quick to recognize great mentoring, excellent support and collaboration, and ample resources as keys to their success — in addition to hard work and a little luck.

Harith Rajagopalan, recipient of the top award, named for triple-Hopkins alum Michael Shanoff, says, "With this award comes the realization that even though being a research trainee is extremely challenging, there is a light at the end of the tunnel, and the people who win these awards are representative of all the people who've had experiments fail and projects that appear to be aimless, and then have overcome it all."

While the "grunt work" of developing new experimental systems isn't usually the stuff of glory, using them can open entire new fields of inquiry and in the last year has allowed Hopkins' young investigators to prove or disprove scientific ideas no one could test before. Here are a sampling of this year's awardees and their projects.


Harith Rajagopalan, an M.D./Ph.D. candidate in the Cellular and Molecular Medicine Program, received the prestigious Michael A. Shanoff Re-search Award for his project "Inactivation of hCDC4 can cause chromosomal instability." With mentor Christoph Lengauer, Rajagopalan found what is believed to be the first common genetic cause for chromosomal instability, a hallmark of most cancer cells in which the number of chromosomes varies dramatically from normal cells.

"We solved a 100-year-old question about the origin of chromosomal instability in certain colon cancers and have proven that a genetic mutation is at fault," says Rajagopalan, a graduate of Stanford University.

Rajagopalan sequenced more than 190 colon tumors and discovered mutations in a gene whose protein product, called hCDC4, binds to and degrades a cell cycle regulator called cyclin E. The findings, published in the March issue of Nature, show that hCDC4 mutations occur frequently — in 12 percent of colon tumors in their studies. The mutations begin to appear in small polyps or adenomas, lesions that may become cancerous in 10 to 20 years.

"We found that cyclin E levels rise in colon cancer cell lines with inactivated hCDC4 because the mutated hCDC4 protein can't bind to cyclin E, but these cell lines also gain and lose chromosomes much faster than cells with normal hCDC4," says Rajagopalan, who expects to finish his program next year.
— Vanessa Wasta


Daniel R. Southworth received a Paul Ehrlich Research Award for his project "Identification of ribosomal control elements involved in translocation," conducted with Rachel Green, an associate professor of molecular biology and genetics and associate investigator of the Howard Hughes Medical Institute.

Southworth, who recently defended his Ph.D. dissertation, studied how the bacterial ribosome controls movement of messenger RNA as proteins are built. A complex of RNA and proteins, the ribosome does three things: It threads the messenger RNA molecules through its center (a process known as translocation), "reads" the RNA's instructions and assembles the called-for protein. Disruption of any of the three events causes an improper protein to be made.

In the Journal of Molecular Biology in 2002, Southworth first reported that stripping the bacterial ribosome core of regulators thought essential for RNA "threading" still allowed proteins to be built. Then, in Molecular Cell in 2003, Southworth and graduate student Anthony Cukras identified two core bacterial ribosome proteins, called S12 and S13, which regulate proper RNA threading. "Daniel has provided a mechanism for 30-year-old unexplained observations," Green says.

His findings have helped establish that the ancestral ribosome was an RNA machine, with protein regulators added later in evolution. Moreover, since the ribosome is a major target for many antibacterial drugs, understanding its basic controls might allow design of new antibiotics, says Southworth, a graduate of the University of California, Santa Cruz.

Green's first student to obtain a graduate degree at Hopkins, Southworth will continue his studies as a postdoctoral fellow at the University of California, San Francisco.
— Diane Bovenkamp


Postdoctoral fellow Samer Hattar received the Albert Lehninger Research Award for his project "Melanopsin cells: Novel photoreceptors involved in non-image-forming visual functions," conducted with King-Wai Yau, professor of neuroscience and a Howard Hughes Medical Institute investigator. Hattar's research focused on understanding how light regulates the mammalian internal clock.

Hattar uncovered a third class of cells in the retina that detect light, ending the monopoly of rods and cones, which for nearly 150 years were thought to be the eye's only light-detecting cells. In a complex series of experiments with knock-out mice, Hattar discovered that retinal cells making the protein melanopsin also detect light. These cells, he found, send information about light intensity, help control non-image-forming functions of the eye, such as the size of the pupil, and give the brain information to figure out whether it's day or night.

"Since I was a biochemistry graduate student, I am very happy to have received an award named after the famed biochemist Albert Lehninger," says Hattar, who notes that a healthy, supportive and collaborative environment were keys to his research success at Hopkins.

Hattar is gearing up to establish his own laboratory, at a place to be determined. His work will focus on how the three light-detecting cells together help regulate aspects of mammalian behavior such as sleep, mood, alertness and seasonal affective disorder, commonly known as the "winter blues," possibly leading to better treatments for jet lag, depression and sleep disorders.
— Runa Musib

For a complete list of Young Investigators' Day award recipients and the schedule of events, see below.


16 Researchers To Be Honored For Their Contributions

2004 Young Investigators' Day
Thursday, April 8, 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

4:05 p.m. Student lectures

The Michael A. Shanoff Research Award
Harith Rajagopalan, M.D./Ph.D. candidate, Cellular and Molecular Medicine Graduate Program
"Inactivation of hCDC4 can cause chromosomal instability"
Sponsor: Christoph Lengauer, Molecular Genetics Laboratory, Department of Oncology

The David Israel Macht Research Award
Hao Jiang, Ph.D. candidate, Graduate Immunology Program "A detailed molecular mechanism for the linkage of V(D)J recombination to the cell cycle"
Sponsor: Stephen Desiderio, Department of Molecular Biology and Genetics

The Martin and Carol Macht Research Award
Sarah White, Ph.D. candidate, Cellular and Molecular Medicine Graduate Program
"Human Ufd2 ubiquitinylates securin and regulates sister chromatid separation"
Sponsor: Antony Rosen, Department of Medicine, Division of Rheumatology

The Hans Joaquim Prochaska Research Award
Jason Pellettieri, Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program
"Regulation of embryonic gene expression by protein degradation"
Sponsor: Geraldine Seydoux, Department of Molecular Biology and Genetics

4:45 p.m. Presentation of student awards

The Nupur Dinesh Thekdi Research Award
Rowena McBeath, M.D./Ph.D. candidate, Cellular and Molecular Medicine Graduate Program
"Commitment of stem cell fate by cell shape, cytoskeletal tension and RhoA"
Sponsor: Christopher S. Chen, assistant professor, Department of Biomedical Engineering

The Alicia Showalter Reynolds Research Award
Joseph W. Lewcock, Ph.D. candidate, Biochemistry, Cellular and Molecular Biology Graduate Program
"A feedback mechanism regulates mono-allelic odorant receptor expression"
Sponsor: Randall R. Reed, Department of Molecular Biology and Genetics

The Mette Strand Research Award
Timothy Hefferon, Ph.D. candidate, Predoctoral Training Program in Human Genetics and Molecular Biology
"New insights into the role of cis-acting sequences in the splicing of a constitutive exon"
Sponsor: Garry Cutting, Institute of Genetic Medicine

The Paul Ehrlich Research Awards
Shih-Chun Lin, Ph.D. candidate, Neuroscience Graduate Program
"Synaptic signaling between neurons and oligodendrocyte precursor cells"
Sponsor: Dwight E. Bergles, Department of Neuroscience

Daniel Southworth, Ph.D. candidate, Biochemistry,
Cellular and Molecular Biology Graduate Program
"Identification of ribosomal control elements involved in translocation"
Sponsor: Rachel Green, Department of Molecular Biology and Genetics

Gyanu Lamichhane, Ph.D. candidate,
Cellular and Molecular Medicine Graduate Program
"Genes essential for pathogenesis of mycobacterium tuberculosis"
Sponsor: William R. Bishai, Department of Medicine, Division of Infectious Diseases

5 p.m. Postdoctoral lectures

The Helen B. Taussig Research Award
Elizabeth A. Hunt, postdoctoral fellow
"Simulation of pediatric cardiopulmonary arrests: Identification of errors"
Sponsor: Peter Pronovost, Department of Anesthesiology and Critical Care Medicine

The W. Barry Wood Jr. Research Award
Hongbo R. Luo, postdoctoral fellow
"Inositol pyrophosphates as novel intracellular signaling molecules"
Sponsor: Solomon Snyder, Department of Neuroscience

5:20 p.m. Presentation of postdoctoral awards

The Daniel Nathans Research Award
Jeroen Pasterkamp, postdoctoral fellow
"A novel role for integrins in semaphorin signaling"
Sponsor: Alex L. Kolodkin, Department of Neuroscience

The Alfred Blalock Research Award
Alberto Bardelli, postdoctoral fellow
"Kinome in colorectal cancers"
Sponsor: Victor Velculescu, Molecular Genetics Laboratories, Department of Oncology

The Albert Lehninger Research Award
Samer Hattar, postdoctoral fellow
"Melanopsin cells: Novel photoreceptors involved in non-image-forming visual functions"
Sponsor: King-Wai Yau, Department of Neuroscience

The A. McGehee Harvey Research Award
Khurram Nasir, postdoctoral fellow
"Coronary atherosclerosis and premature family history of coronary heart disease"
Sponsor: Roger S. Blumenthal, Department of Medicine, Division of Cardiology

5:30 p.m. Poster presentation and reception, PCTB Greenhouse


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