SOM Honors Young Researchers
Daniel Southworth, recipient of a
Paul Ehrlich Research Award, in the laboratory with mentor
PHOTO BY HPS/WILL KIRK
Young Investigators' Day recognizes innovative,
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
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
"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
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
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
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,
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
— 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
2004 Young Investigators' Day
Thursday, April 8, Mountcastle Auditorium of the
Preclinical Teaching Building on the East Baltimore
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
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
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
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
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
The Paul Ehrlich Research Awards
Shih-Chun Lin, Ph.D. candidate, Neuroscience Graduate
"Synaptic signaling between neurons and oligodendrocyte
Sponsor: Dwight E. Bergles, Department of
Daniel Southworth, Ph.D. candidate,
Cellular and Molecular Biology
"Identification of ribosomal control elements involved in
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
Sponsor: William R. Bishai, Department
of Medicine, Division of Infectious
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
The W. Barry Wood Jr. Research Award
Hongbo R. Luo, postdoctoral fellow
"Inositol pyrophosphates as novel intracellular signaling
Sponsor: Solomon Snyder, Department of
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
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
GO TO APRIL 5, 2004
TABLE OF CONTENTS.
GO TO THE GAZETTE