Contact: Alexander Shtifman
Phone: 617-713-8989
alex...@childrens.harvard.edu

Sun Hur Ph.D was awarded the 2015 Vilcek Prize for Creative Promise in Biomedical Science. The Vilcek Prizes for Creative Promise were established in 2009 to encourage and support young immigrants who have already demonstrated exceptional achievements, and who often face significant challenges early in their careers.

About Sun Hur

Self-discovery is a theme that unites Sun Hur's life and work.  Growing up with a passion for physics, Hur pursued a scientific career in chemistry before launching her own research group in biology. Today, Hur, an Associate Professor at Harvard Medical School, uses her considerable intellectual gifts to uncover how the immune system distinguishes self from non-self.  Her work bears implications for the treatment of inflammatory and autoimmune diseases.

Hur's foray into science began at home in Seoul, South Korea: Her father, an electronics engineer, was a guiding influence in her childhood, emphasizing problem solving over passive learning.  Her mother forsook a career as a chemist to help provide a nurturing home for her children.  From a young age, Hur was intrigued by order and chaos, and it was perhaps this early predilection that led to a lasting obsession with patterns observed in nature and artifice.  While studying physics in college, she learned that mathematical rules can describe natural phenomena; while painting still life in her studio, she realized that stories often shape the ostensibly random arrangement of objects in a scene.

While pursuing a bachelor's degree in physics at Seoul's Ehwa Womans University, a private women's university, Hur became enchanted with biological systems, which often resist elegant mathematical formulation.  To explore her interest in biology, she moved to the United States in 2000 for an undergraduate summer research program at Woods Hole Oceanographic Institute and an exchange program at the University of California, Santa Barbara, where she completed her undergraduate degree.

Braving culture shock and a formidable language barrier, Hur joined the lab of Santa Barbara organic chemist Thomas Bruice, known for his work on the computational analysis of enzyme reactions.  The experience offered an opportunity to use theory to interpret experiments and marked a step toward a biological research career.  "Back in Korea, I was doing a lot of programming in the applied mathematics department, so I was familiar with computers," she says.    Before long, she enrolled for a PhD with Bruice, exploring the molecular mechanisms of enzyme reactions. In particular, Hur's computational studies helped settle a long-standing question over whether all enzymes catalyze reactions by stabilizing a chemical intermediate called the "transition state," which appears during the conversion of reactants into products.  Her PhD work, completed in just two years, uncovered several examples to the contrary.  "That was something that the field did not expect," she says.

Despite her substantial contributions to enzymology, Hur felt an undercurrent of dissatisfaction with purely theoretical work, which relied on others' experimental data.  So she began a postdoctoral fellowship in experimental enzymology with University of California, San Francisco, structural biologist Robert Stroud.  There, she used X-ray crystallography to unravel the molecular structure of an enzyme that modifies a key player in protein synthesis in all cells.  Computational simulation of the structure provided clues to the exquisite specificity with which the enzyme recognizes its substrates, solving a mystery that had perplexed enzymologists.

The focus of Hur's work in Stroud's lab-RNA molecules found in some pathogenic viruses-heralded a new phase in her career and defined her research specialty for the coming years.  So when she launched her own lab as a 29-year-old assistant professor at Harvard Medical School in 2008, she continued to study RNA-but with the clear goal of performing clinically relevant research. She explored how the innate immune system of animals recognizes invaders, in particular disease-causing viruses that generate a double-stranded RNA during replication.  Because double-stranded viral RNA is typically longer than that naturally found in cells, Hur surmised that a mechanism that uses length to distinguish between viral and cellular RNA might underlie the immune system's discriminatory power.

Through biochemical, structural, and computational studies, Hur showed that one member of a previously discovered group of proteins called pattern recognition receptors, which recognize consistent molecular designs in pathogens, might indeed act as a ruler, measuring the length of double-stranded RNA to divine its source.  The protein, called MDA5, assembles into a filament along the length of the RNA in question, allowing it to size up the suspect.  If the RNA is deemed to be of viral origin, the protein triggers the appropriate defense mechanism to dispatch the virus. (A related protein called RIG-I, Hur found, uses a different mechanism of RNA detection and, hence, may target distinct viruses.)

Further studies revealed that genetic mutations in MDA5 can lead to its malfunction, locking the molecule in its filamentous state longer than usual and setting off runaway immune reactions that can damage cells.  "What we found is that the mutations confuse the MDA5 protein, and the self-RNA is recognized by the mutant MDA5 as non-self," Hur says.  The result is a rare inflammatory disorder called Aicardi-Goutieres Syndrome, whose symptoms include intellectual disability.  "We're following up on this work by asking if there are specific [cellular] RNA molecules that stimulate the MDA5 signaling," she adds.  Pursuing the therapeutic implications of that possibility, Hur has teamed up with a pharmaceutical firm to find drugs that can suppress aberrant signaling by MDA5.

The clinical impact of Hur's work may extend beyond inflammatory disorders.  Hur is now exploring ways to use genetic engineering to target gene fusion events that underlie some cancers. (Chronic myeloid leukemia, a deadly blood cancer, for example, is caused when two chromosomes in white blood cells exchange fragments, resulting in a hapless fusion of genes that are normally kept apart.)  By engineering an artificial protein that targets the product of such potentially cancer-causing gene fusions, Hur hopes to trigger immune defense mechanisms that kill rogue cells harboring the fusions.

Hur's scientific promise has been previously recognized; she has earned a Pew Scholarship in Biomedical Science and a New Investigator Award from the Massachusetts Life Sciences Center.  She ascribes her early success and continuing rise to the willingness of her mentors to welcome a relative novice into their labs and nurture her nascent scientific career.

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