Graduate Student Profile: Anshu Rastogi
The Key to Back Pain: Is It In Our Genes?
Hometown: Bowie, Md.- B.S.: Biology, University of Maryland
- Advisor: Assistant Professor Adam Hsieh
- Started Program: Fall 2004
Could the cause of back pain be in our genes, preventable or stoppable by rendering the culprits inactive? Could a certain type of cell we lose in childhood, and the genes it contains, help repair and heal us as adults? Graduate Program in Bioengineering student Anshu Rastogi wants to find out.
Rastogi works with her advisor, Assistant Professor Adam Hsieh, in the Orthopaedic Mechanobiology Lab, where they hope to discover and understand the causes leading to intervertebral disc degeneration. Intervertebral discs are water balloon-like cushions between the bones (vertebrae) in our spines that absorb impact and prevent them from rubbing together. Disc degeneration is the leading cause of back pain in the U.S., affecting about 80% of the population at some point in their lives.
After earning her B.S. in biology and before returning to school, Rastogi, a UMD alumna, worked at Baxter, a company specializing in medical devices, pharmaceuticals and biotechnology. There, she developed meningitis combination (CYW) vaccines. "It involved lots of protein chemistry, process and research development," she recalls. "It was, in a sense, a lot of bioengineering." Interested in conducting more of her own research, she decided to pursue a Ph.D. and considered her options. "It was funny, because when I read Maryland's bioengineering program brochure, I thought, 'That's exactly what I did [at Baxter]!'"
Rastogi's background made her a good match for the program, but instead of continuing her work on vaccines, she chose to use her experience to explore an entirely new direction. She explains how she made the move to studying intervertebral disc degeneration: "Dr. Hsieh had just joined the faculty. He had a mechanical background and was looking for a biologist to carry on the genetic aspect of his work. He was also interested in RNA interference like I was, so we brought our skills together. We have the mechanics going on [in our research] as well as the biology. We're complimentary, so it's just worked out really well."
While mechanical stresses and injuries can cause or contribute to intervertebral degeneration—and are researched in the Orthopaedic Mechanobiology Lab—as the biologist on the team, Rastogi's mission is to examine intervertebral disc cells and discover which genes may be responsible causing this widespread problem, and whether tissue or genetic engineering could correct or prevent it.
In exploring the cause, Rastogi studies a class of genes called MMPs (matrix metalloproteinase), which are thought to be involved in the degeneration process. She uses a technique called RNA interference, in which she introduces a new piece of genetic material that "knocks down"—destroys or "turns off"—these genes without killing the intervertebral disc cells in which they reside. Once the MMP genes are out of action, she can then observe whether the cells still go through a degeneration cycle.
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Microscope images taken at 400x magnification: a) Notochordal cells in microlayer at 3 days; b) detailed view of notochordal cells at 3 days. |
Rastogi is also exploring whether other genes in intervertebral disc cells may be able to prevent degeneration. Within the spine there are several types of cells, including notochordal, chondrocyte (cartilage), and nucleus pulposus. In humans, notochordal cells die off at about age 4, and are replaced by chondrocytes. Studies have found that there are certain genes found only in the notochordal cells. Rastogi would like to know whether these genes, or the notochordal cells as a whole, play a role in maintaining the overall health of the intervertebral discs.
"If we placed notochordal cells into an unhealthy disc," she asks, "would that help maintain the health at what it is, make it worse, make it better? My work is about characterizing the genes within the disc [cells] to find out which ones play a role in degeneration, as well as which might prevent it."
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Tissue clusters of disrupted nucleus pulposus cells embedded in alginate at 2 weeks in culture, at 400x magnification. CellTracker Green was used to stain the cell and DAPI was used to stain the cell nucleus. |
Collecting the cells and genes Rastogi needs for her research is a time-consuming process. Currently, she primarily uses nucleus pulposus cells taken from rats. After extracting the contents of a rat's tiny intervertebral disc, she separates the cells she needs from the gelatinous matrix of proteins and collagens in which they reside, as this extracellular material can interfere with certain tests. She must then culture the cells, which presents another challenge: "When you put the cells onto tissue culture plastic in a single layer," she explains, "they flatten out. This is obviously not how they are physiologically—in the body they have the surrounding scaffold [of proteins and collagens] propping them up and keeping them round. One school of thought is that by working this way, you're changing the cells and they're not going to act as they do when they're in the body." She is therefore exploring other methods of cell culture that place the cells in a simple alginate gel to simulate the physical qualities of environment found in the intervertebral discs, allowing harvested cells—and the delicate genes they hold—to maintain their integrity over longer periods of study.
Choosing the Graduate Program in Bioengineering at Maryland was an easy decision for her, and she recommends it. "I'm from this area and came to UMD as an undergrad as well, so I knew what a big hub for research the school is. The [A. James] Clark School [of Engineering] is ranked well on a national level and BioE is booming right now. We have so many new faculty members doing research in many different fields. Some of the stuff going on here is amazing. And being in [the Washington, D.C.] area allows collaborations with a lot of other academic institutions and industries."
She says the relative youth of the program, and its steady growth, have been big factors in her enjoying her graduate experience. "You can help shape [the program] for students joining it in the future," she says. "And it's still fairly small, which means you aren't just another student."
Rastogi isn't sure whether she would like to return to industry or remain in academia after earning her Ph.D., but she is contemplating her options: "I hadn't considered working in academia until I started here, and the experience has been great so far. The campus environment is energizing. Industry was good, but I can't say it was a great job for me, because I wasn't doing my own work. Whatever comes down the pipeline, you have to work on. You have to deal with a lot of stuff that's more about the company than about the research."
When asked what advice she has for undergraduates considering graduate studies in bioengineering, she sums it up quickly: "Do it!...Seriously though," she adds, "it's something you really have to want to do, or you won't enjoy any part of it. It's not an easy task to accomplish. Look into a variety of programs and schools to make sure you find the right fit. I was applying to physical therapy programs before I came into this one. Without having gone through that, I wouldn't have known that it wasn't for me. This is."
Rastogi says the most rewarding outcome for her research would be to do something that will benefit society. "Disc degeneration affects so many people. If my work can help in the treatment of back pain through tissue engineering techniques, that will be a very big achievement."
