Fraley nets $500K Burroughs Wellcome Fund award for microfluidics work

Stephanie Fraley (Photo: Homewood Photography)

Stephanie Fraley (Photo: Homewood Photography)

A Johns Hopkins research fellow who is developing novel approaches to quickly identify bacterial DNA and human microRNA has won the prestigious $500,000 Burroughs Wellcome Fund (BWF) Career Award at the Scientific Interfaces. The prize, distributed over the next five years, helps transition newly minted PhDs from postdoctoral work into their first faculty positions.

Stephanie Fraley is a postdoctoral fellow working with Samuel Yang, MD, in Emergency Medicine/Infectious Disease at the Johns Hopkins School of Medicine and Jeff Wang, PhD, in Biomedical Engineering with appointments in the Whiting School of Engineering and the medical school. The goal of her work is to develop engineering technologies that can diagnose and guide treatment of sepsis, a leading cause of death worldwide, while simultaneously leading to improved understanding of how human cells and bacterial cells interact.

“Sepsis is an out of control immune response to infection,” Fraley said. “We are developing tools that are single molecule sensitive and can rapidly sort and detect bacterial and host response markers associated with sepsis. However, our devices are universal in that they can be applied to many other diseases.”

Fraley is using lab-on-chip technology, also known as microfluidics, to overcome the challenges of identifying the specific genetic material of bacteria and immune cells. Her technology aims to sort the genetic material down to the level of individual sequences so that each can be quantified with single molecule sensitivity.

“Bacterial DNA is on everything and contamination is everywhere, so trying to find the ones associated with sepsis is like the proverbial search for the needle in the haystack,” Fraley said. “With microfluidics, we can separate out all the bacterial DNA, so instead of a needle in a haystack, we have just the needles.”

Another advantage to Fraley’s novel technology is that it will assess all the diverse bacterial DNA present in a sample, without presuming which genetic material is important. “Bacteria are constantly evolving and becoming drug resistant,” she said. “With this technology, we can see all the bacterial DNA that is present individually and not just the strains we THINK we need to look for.”

Fraley’s award will follow her wherever her career takes her. The first two years of the prize fund postdoctoral training and that last three years help launch her professional career in academia. During the application process, she had to make a short presentation on her proposal to BWF’s panel of experts. “It was like the television show ‘Shark Tank’ but for scientists,” she laughs. “ The panelists gave me many helpful suggestions on my idea.”

Fraley earned her bachelor’s degree in chemical engineering from the University of Tennessee at Chattanooga and her doctorate in chemical and biomolecular engineering with Denis Wirtz, professor and director of Johns Hopkins Physical Sciences-Oncology Center. Wirtz is associate director for the Institute for NanoBioTechnology and Yang and Wang also are INBT affiliated faculty members.

BWF’s Career Awards at the Scientific Interface provides funding to bridge advanced postdoctoral training and the first three years of faculty service. These awards are intended to foster the early career development of researchers who have transitioned or are transitioning from undergraduate and/or graduate work in the physical/mathematical/computational sciences or engineering into postdoctoral work in the biological sciences, and who are dedicated to pursuing a career in academic research. These awards are open to U.S. and Canadian citizens or permanent residents as well as to U.S. temporary residents.

Shaping up nanoparticles for DNA delivery to cancer cells

Hai-Quan Mao, 2012 Johns Hopkins Nano-Bio Symposium. Photo by Mary Spiro

To treat cancer, scientists and clinicians have to kill cancer cells while minimally harming the healthy tissues surrounding them. However, because cancer cells are derived from healthy cells, targeting only the cancer cells is exceedingly difficult. According to Dr. Hai-Quan Mao of the Johns Hopkins University Department of Materials Science and Engineering, the “key challenge is between point of delivery and point of target tissue” when it comes to delivering cancer therapeutics. Dr. Mao spoke about the difficulties of specifically delivering drugs or genetic material to cancer cells at the 2012 Johns Hopkins University Nano-Bio Symposium. Scientists had originally thought they could create a “magic bullet” to patrol for cancer cells in the body. However, this has not been feasible; only 5 percent of injected nanoparticles reach the targeted tumor using current delivery techniques. Simply put, scientists need to figure out how to inject a treatment into the body and then selectively direct that treatment to cancer cells if the treatments are to work to their full potential.

With this in mind, Dr. Mao and his research team aim to optimize nanoparticle design to improve delivery to tumor cells by making the nanoparticles more stable in the body’s circulatory system. Mao’s group uses custom polymers and DNA scaffolds to create nanoparticles. The DNA serves dual purposes, as a building block for the particles and as a signal for cancer cells to express certain genes (for example, cell suicide genes). By tuning the polarity of the solvent used to fabricate the nanoparticles, the group can control nanoparticle shape, forming spheres, ellipsoids, or long “worms” while leaving everything else about the nanoparticles constant. This allows them to test the effects of nanoparticle size on gene delivery. Interestingly, “worms” appear more stable in the blood stream of mice and are therefore better able to deliver targeted DNA. Studies of this type will allow intelligent nanoparticle design by illuminating the key aspects for efficient tumor targeting.

Currently, Dr. Mao’s group is extending their fabrication methods to deliver other payloads to cancer cells. Small interfering ribonucleic acid (siRNA), which can suppress expression of certain genes, can also be incorporated into nanoparticles. Finally, Mao noted that the “worm”-shaped nanoparticles created by the group look like naturally occurring virus particles, including the Ebola and Marburg viruses. In the future, the group hopes to use their novel polymers and fabrication techniques to see if shape controls virus targeting to specific tissues in the body. This work could have important applications in virus treatment.

Story by Colin Paul, a Ph.D. student in the Department of Chemical and Biomolecular Engineering at Johns Hopkins with interests in microfabrication and cancer metastasis.