Hopkins' young researchers honored for their contributions


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, 2004, The Johns Hopkins University 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 Preclinical 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. 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.

This year's award recipients, like those from previous years, 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 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 post-docs, 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 headed by Se-Jin Lee, M.D., Ph.D., aren't just about honoring people close to Hopkins. Recipients say they get a confidence boost from the recognition, and the entire celebration helps encourage all students and post-docs to continue the legacy of the awards' namesakes.

"Young Investigators' Day encourages those whose research careers are just beginning to bloom by emphasizing independent thinking, keen observation, perseverance and hard work as keys to research success at all levels of training," says Rowena McBeath, an M.D./Ph.D. candidate in Cellular and Molecular Medicine. McBeath received this year's 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 awards also give family members the chance to celebrate with young researchers without needing to understand, say, the genetics 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, Ph.D., 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!"

All of 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. 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 Research Award for his project "Inactivation of hCDC4 Can Cause Chromosomal Instability." With mentor Christoph Lengauer, M.B.A., Ph.D., Rajagopalan answered a hundred-year-old question by finding 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 differs dramatically from normal cells.

Rajagopalan sequenced DNA from 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, a Stanford graduate who expects to finish his program next year.

Daniel R. Southworth received a Paul Ehrlich Research Award for his project "Identification of Ribosomal Control Elements Involved in Translocation," conducted with Rachel Green, Ph.D.

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 thirty-year-old, unexplained observations," says Green.

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 anti-bacterial 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.

Postdoctoral fellow Samer Hattar, Ph.D., 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, Ph.D. 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.

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." The results could lead to better treatments for jet lag, depression and sleep disorders.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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