Graduate Student Profile: Ian Gifford
Using Nuclear Medicine to Combat Prostate Cancer
Hometown: Garret Park, Maryland- B.S.: Chemistry, University of Michigan Ann Arbor
- Advisor: Professor Mohamad Al-Sheikhly (Materials Science and Engineering, Graduate Program in Bioengineering)
- Started Program: Fall 2005
In the fight against cancer, scientists all over the world are inventing and refining their means of attack. Ian Gifford, advised by Professor Mohamad Al-Sheikhly (Department of Materials Science and Engineering, Graduate Program in Bioengineering), is addressing tiny packages of a drug to cancer cells, and using irradiation to trigger their disease-fighting effects. Along the way, he has worked with Al-Sheikhly and others to establish new nuclear medicine facilities for students and researchers to come.
Gifford hadn't originally planned on a career in bioengineering. He first worked for Al-Sheikhly in the summer of 2004, while he was an undergraduate majoring in chemistry at the University of Michigan. "I didn't quite know what I wanted to do when I graduated," he admits. "Although I enjoyed chemistry, I really wanted to branch out into biology and pursue a field where my research could directly be used to help people. [Professor Al-Sheikhly] said he could use my help in the lab if I wanted to work here while I figured things out." Taking him up on the offer, Gifford returned to the Clark School in January 2005.
"I realized I really liked this type of research," he explains. "I was interested in working with doctors and patients but not so much in actually being a medical doctor. Dr. Al-Sheikhly has a lot of background in biology, and he was looking for a student who was interested in bringing biology into his lab. We came together at the perfect time." Gifford decided to apply to the Graduate Program in Bioengineering, and was accepted to start in the Fall 2005 semester.
Gifford's research centers around boron-neutron capture therapy, a bimodal treatment currently in use around the world for patients with brain tumors. His goal is to adapt it for the treatment of prostate cancer, which, according to the American Cancer society, is the second most common in American men, affecting 1 in 6 during the course of their lifetimes. (American Cancer Society web site.)
In this type of therapy, doctors inject a drug specifically designed to seek out specific types of cancerous cells, resulting in fewer side effects for the patient. "Only [affecting cancerous cells] might be overly optimistic," Ian explains, "but the ratio of affected tumor cells to normal cells needs to be as high as possible."
The first part of Gifford's research involves cultivating both cancerous and healthy human prostate cells, and comparing their behavior when exposed to a boron-containing drug under identical conditions. Gifford is looking for the conditions under which the cancer cells take up the greatest amount of the drug, and the healthy cells the least. He notes the mechanisms and kinetics of absorption, the optimal temperature for the process, and how much of the drug accumulates or is released.
There are various ways to introduce drug molecules into a cell, including simply adding them into the medium (or body) in which the cells are growing. But this, Gifford explains, is not always effective or precise, and can lead to harmful side effects as good cells are treated along with the bad. "You could just hope that the cancer cells will take in the drug and the healthy cells won't," he explains, "or you can wrap up the drug molecule in a special kind of package that will enhance the delivery to cancer cells. When you're selectively targeting cancer cells, that packaging is very important. You want one that only they will find appealing."
Gifford starts by making liposomes, spherical containers also known as "vesicles" that are made out of a combination of lipids (a type of fat molecule), natural cholesterol, and a native cholesterol mimic. The mimics, which Gifford receives from a collaborator on the project, look exactly like natural cholesterol except unlike the real thing, each carries a cluster of boron atoms attached to one end, called a "cage" because if its configuration.
When the liposome packages come into contact with low density lipoproteins (LDL, carriers of bad cholesterol), which occur naturally in the body, the mimic detaches from the liposome, and, still carrying its boron cage, attaches to the LDL. At this time, no one is certain why this "handoff" occurs, but it is a crucial step—it is the LDL that will make the final delivery of the drug to the cancerous cells.
The mimic-containing LDL molecules are exactly the sort of package cancerous cells like to receive. But why? "That's actually one of the big questions in cancer therapy," Ian tells us. "What's different about cancer cells than normal cells?" While the question has not yet been fully answered, scientists do know that cancer cells have a higher quantity of low-density lipoprotein receptors—protrusions that "grab" lipoproteins—on their outer membranes, making them especially receptive to LDL. Some scientists believe that the rapidly dividing and growing cancer cells need the cholesterol to build their outer membranes. When presented with a tempting lipoprotein package, the cancer cell accepts it, taking up the drug along with it. Once inside, the LDL package degrades, releasing the drug exactly where it needs to be. Meanwhile on the outside, the body will naturally break down and dispose of the original liposome packages.
The second part of Gifford's research involves the University of Maryland's nuclear training and research reactor, which is being specially refitted for work in nuclear medicine. The prostate cancer-fighting drug he works with is not in itself harmful to cells, cancerous or otherwise. But when the drug is irradiated with neutrons generated by the reactor, its boron atoms burst apart, creating a high-intensity explosion confined mostly or entirely to the cell in which it is contained. This kind of interaction is called a high linear energy transfer (High LET).
Under ideal circumstances, only cancerous cells will have taken up the drug in its lipoprotein packages, and only they, not surrounding healthy cells, will fall victim to the tiny explosions. The drug molecules also require less radiation to trigger their bursting than a patient would receive in typical radiation therapy. The overall result would be a more accurate style of treatment with fewer side effects.
Gifford's work has received enough interest that not only has the University's reactor been modified to support the study of nuclear medicine, he was also tasked by Professor Al-Sheikhly and the Graduate Program in Bioengineering to design a facility to support his and future students' work. The new Biophysical and Polymer Radiation Laboratory will provide a cell culture environment adjacent to the reactor.
Gifford is excited by this responsibility and his position as one of the people pioneering nuclear medicine in the program and the department. "When I came here, Dr. Al-Sheikhly was very interested in shifting the focus of our reactor to nuclear medicine. The Graduate Program in Bioengineering let me get involved in that because students can blaze their own trails rather than follow a set path. Their approach is,'What do you want to do, and can we do it here?' which is a wonderful philosophy in my opinion. Having a reactor is the big limiting step in this type of research. It's the hardest thing to get, and it's the most expensive, so if you have that piece, if you have students who are interested, and if you have financial backing, you have a rare opportunity to put together a facility that can study nuclear medicine."
He also has high hopes for his research and the legacy of his work. The most rewarding outcome, he says, would be to have the Food and Drug Administration (FDA) approve the drugs used in his research for cancer treatment, and see an improved method of therapy available to people suffering from the disease. He's also proud of the new Biophysical and Polymer Radiation Laboratory: "It's great to have been a huge part in developing a facility here, and have interested students come here and do this type of work, using the things that I helped build."
Gifford cites the relationships he's built as one of the highlights of his graduate experience. "The advice I've gotten from Dr. Al-Sheikhly and other faculty members has been fantastic—I've never had this sort of student-teacher relationship where it's not just academic; it's also mentoring, friendship, and networking." He has also enjoyed learning how to be a scientist in a global community in which he has to network and communicate with peers, industry, the public, the government, and other academic institutions.
He describes the graduate program as "fantastic": "The University of Maryland has clearly made a strong commitment to become one of the best programs in the country. You can see that through the quality of the students they've admitted, in the facilities, and in the faculty. If there's something you're interested in doing, the faculty do everything they can to help you realize it. Many of them are interdisciplinary, which is really valuable because the most interesting and groundbreaking research requires an understanding of many different fields."
After graduating, Gifford intends to focus on an academic career. In the spring of 2007, he was one of only 20 students chosen to participate in the Clark School's new Future Faculty Program, which was created to prepare graduate students for academic careers in top-50 engineering schools. The program includes seminars, a teaching practicum, and a research mentoring practicum.
"There are many responsibilities that accompany a tenure-track position," says Gifford, "and I hope [the Future Faculty Program will] help with the transition from mentee to mentor. There are certain skills that young faculty members are expected to have, but the development of them as a graduate student is often overlooked. This program focuses on these skills, grooming students for future success."
As much as he enjoys his work, Gifford also likes living in the Washington, D.C. metro area, and makes time to experience what the nation's capital and the region have to offer: an active social life, diverse restaurants, clubs and bars, local music, great museums, and sporting events. He is also involved in intramural basketball on campus.
Asked what advice he has for undergraduates considering graduate studies in bioengineering, Gifford suggests not rushing into the decision. It's OK not to know exactly what you want to do right after graduation, he says, and encourages people to visit different programs at different universities, or try working in a lab or two to see what feels right. He also encourages undergraduates not to worry if they haven't majored in bioengineering: "Even if you think your discipline wouldn't be helpful in bioengineering, you could bring something completely different to the field that no one else is thinking of." Finally, he recommends people contact current students of programs in which they are interested. "I can't speak for anyone else," he says, "but in my case I've had such a good time here at Maryland and I love talking about how much I like it!"
