The odds are strikingly high that you or someone you know has been directly affected by cancer. It is estimated that 4 out of 10 people will develop cancer at some point in their lives.
Sheereen Majd, Penn State assistant professor of biomedical engineering, has focused her research career on the study of cell membranes, a key battleground in the fight to make cancer a more treatable disease.
All animal cells are surrounded by a membrane that gives the cell its shape and functions as the cell’s gatekeeper, regulating what passes in and out. Although extremely effective, cell membranes are also quite delicate. A single membrane is approximately 5 nanometers thick. In comparison, it would take nearly 20,000 membranes to equal the width of a single human hair.
Human cell membranes are complicated structures, but Majd’s group uses micro- and nanofabrication techniques to make simple membranes that can be used to simulate living cells. By studying the cell membrane components at a single molecule level — a level that would never be visible with a standard microscope — they can, for instance, determine how individual proteins interact with anti-cancer drugs.
One such protein in the cell membrane is called a multi-drug-resistant transporter, and it has been identified as a major obstacle for current cancer treatments. In normal cells, the transporter protein protects the cell from toxins and pathogens. However, in cancer cells this protein is often overexpressed.
“In cancer cells, the chemotherapy reaches the inside of the cell, but the transporter thinks ‘this toxin does not belong here,’ and it begins to pump it out. It will keep pumping it, not allowing any of the chemo to accumulate inside,” Majd said. “Then, for reasons not well understood, the transporter is able to recognize other types of drugs as well, ones with different structures it has never encountered. That’s where the term ‘multiple drug resistance’ comes from. These proteins are actually keeping cancer cells alive.”
Majd and her research group have set themselves the difficult task of modulating the transporter proteins so that chemotherapy drugs can work efficiently. Eliminating the proteins wholesale would be catastrophic, creating free passage for toxic pathogens to enter the brain and central nervous system. The challenge, instead, is to explore ways to modify only the cancer cell membranes. For her work on this project, Majd was awarded The Pittsburgh Foundation’s Young Investigator Research Grant.
A second major research focus in Majd’s lab is designing a drug delivery system that can cross the blood-brain barrier to treat malignant brain tumors, namely, glioblastoma — an aggressive tumor that can quickly spread to other parts of the brain.
The BBB is a sophisticated membrane-like structure that protects the brain and keeps harmful pathogens in the blood from entering. The goal of Majd’s group is to identify a way around the BBB in order to administer injectable drugs directly to the malignancies using her membranes as nanoparticle delivery systems.
“We are trying to package these toxic drugs in such a way that they do not harm anything they come in contact with until they have reached the right cancer cells to destroy,” Majd said.
For this research, she and her group have partnered with Penn State neurosurgeon James Connor to test the feasibility of their drug delivery system. The team was awarded the Grace Woodward Grant for collaborative research in engineering and medicine from the Penn State College of Engineering and the Penn State Milton S. Hershey Medical Center. Although drug delivery systems targeting cancer are an active research field, using membrane-enveloped particles to target brain cancers is relatively new.
The group draws inspiration from nature and attempts to mimic the processes of cell membranes by gathering the right components under the proper conditions and allowing the molecules to self-assemble like living materials.
None of this is easy. The process of developing a plausible hypothesis, creating an experimental setup and testing the hypothesis can take years. Testing proceeds from a simple cell culture grown in 2-D on a flat surface to 3-D cell cultures with more complex components. Only a small proportion of such experiments will be successful. Even fewer experiments will progress to in vivo, or live animal, tests.
“You will have a lot of failed experiments,” Majd said, laughing. “Someone outside of science would think we’re crazy.”
“We also become emotionally attached to our work,” she continued. “It’s what brings us back every day. Anytime we discover something new, we feel like we are the first people to ever find that answer — it is such a beautiful moment. At the end of the day, our jobs translate into papers and patents. But beyond that, we hope to create a product that goes to the market. That is the ultimate success for us. Of course, we fully expect to have a few bumps along the way.”
Majd joined Penn State in 2011 as an assistant professor in the Department of Biomedical Engineering and, in 2012, was appointed to a joint position in the Department of Engineering Science and Mechanics. Her group actively partners with other members of the Penn State academic community, including biomedical engineers, chemical engineers and neuroscientists. More about Majd’s research can be found at www.bme.psu.edu/labs/Majd-lab/.