Research translates to real-life success for student Isaac Lamb

Nothing beats real-life experience, particularly when it comes to developing marketable skills. While it will be a few more years before he hits the job market, it's no different for IUPUI's Isaac Lamb.

A biology and neuroscience double major, Lamb wasted little time setting himself up for medical school. He secured his first research opportunity even before taking his first class in the School of Science at IUPUI, and he has continued to add to his experience with each passing year.

As a first-year student, Lamb was in the Biology Freshman Work Program, learning the fundamentals of lab management, mixing solutions and cleaning. A year later, he joined the Sears Lab at the Indiana University School of Medicine under the watchful eye of Dr. Catherine R. Sears, an opportunity he seized through the Life-Health Sciences Internship program.

He continued working at the Sears Lab as a junior, but he also joined the Distributed Drug Discovery Lab with the Department of Chemistry and Chemical Biology after taking an organic chemistry class. And now he's completing a research project for his senior neuroscience capstone.

With each of those opportunities, Lamb is investigating DNA proteins with immunofluorescence microscopy to find ways to fight emphysema and other lung diseases. He is identifying chemical compounds that could lead to low-cost antibiotics to treat "orphan diseases," those that largely affect people in developing countries due to the prohibitive expense of developing drugs. And he's laying a foundation that, in the long run, could reduce birth defects in babies born to women using antidepressants.

If the technical seems overwhelming, the less-tangible results of his research -- job skills, networking opportunities and experience that helped earn him early admission to the IU School of Medicine -- are actually easier to grasp.

"I find it rewarding. I think it's helped me with my academics," said Lamb, who is also a member of the Honors College and a Bepko scholar. "There's a lot that I experience in my classes that I get to use in the lab. It helps me retain information, too. Things I learned previously come back in my research. It's kind of like a refresher, and it's sharpened because I have a real-life application of it."

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Isaac Lamb presented some of his research at an IUPUI Center for Research and Learning symposium last summer. Photo courtesy of Isaac Lamb

In his words

Sears Lab research

"Your DNA is constantly being bombarded with radiation, and all sorts of things, just from your environment. It's constantly getting damaged, but your body has repair mechanisms and usually fixes it pretty well. Usually -- 99.99 percent of the time -- it's repaired, no problem. One of these repair mechanisms is a protein called XPC. One thing we know is that it's implicated in oxidative damage, which is similar to what you'd see from cigarette smoke. It's theorized that if XPC is repairing damage caused by cigarette smoke, but you don't have XPC, you should see higher rates of lung cancer. You should also see possibly higher rates of emphysema.

"Emphysema is, in layman's terms, when some cells in your lungs die and have less surface area. They're less springy, so they don't absorb air as easily. You're left with shortness of breath. That can make the wheezing sound you think of with emphysema. The thing that causes that is that your cells actually have a pathway. If one detects it has too much DNA damage, it just automatically kills itself, and that's a good thing; you don't want the cell to become cancerous.

"What we found is that XPC increases the rates of the cells killing themselves. It's called apoptosis. The other way, the cell could explode and send all its contents everywhere, and that's bad. But apoptosis nicely puts everything in these little capsules, and it just kind of falls apart. That's good. We found that XPC increases the rates of that. I mostly did this through immunofluorescence microscopy. Basically, you can do some special treatments, and whatever you're looking for, it will glow under fluorescent light. I can say if DNA is fragmented in a certain way, it indicates it's undergoing apoptosis, and this thing will show up as green. I can look at it, all cells will stay in blue, and then I switch the light and see, out of the 1,000 cells that were in this picture originally, how many of them are now green. Then you can calculate the rate of damaged cells killing themselves."

Distributed Drug Discovery Lab

"It's extremely expensive to take a drug from research to market. We're talking millions, maybe billions, of dollars. What this means is that there are certain diseases we could develop a treatment for, but we won't because it's too expensive. These are called orphan diseases. These are often diseases that disproportionately affect developing countries. The people who have these diseases can't afford to pay for an expensive treatment, so no one's going to pay to develop a treatment because no one's going to be able to pay for it in the end. There's a need to come up with a more low-cost method of developing these drugs.

"So we look at cystic fibrosis patients. Because of the way the disease goes, they are at a much higher risk of having bacterial infections. We're developing antibiotics in a low-cost method. Ideally what we'd want to do is develop what's called a pro-drug. Usually, you make a chemical, and it's toxic to the bacteria. The problem is, it's also toxic to people. What we want to do is package it and add things to it so that the bacteria will eat it up, but human cells won't. It's pretty easy to find stuff that's toxic. It's hard to find something that is only toxic to bacteria and not human cells.

"The most exciting part about the D3 Lab is that we have this educational component to it. We look at it and say, 'Hey, I think this thing might work.' Then I'll synthesize a couple of compounds to see what it would look like. Then a biology team will test it on the bacteria and see if it kills it. If it does, we'll design a whole bunch of derivatives, and then we'll have the organic chemistry students, under our supervision, actually make these compounds during their class. They get to not only learn the chemistry that's involved, but also take part in the actual drug-discovery process. Instead of doing these theoretical projects, we're saying, 'We are going to test this. We will submit these to Eli Lilly.'"

Neuroscience capstone

"We work with C. elegans, which is a type of nematode. My project is looking at the impact of SSRIs, or selective serotonin reuptake inhibitors, which are a type of antidepressant. We're exposing these nematodes as an egg, and then we're testing their movement later in life and seeing if it's impacted. It's supposed to be a model of pregnant mothers who are told to get off of SSRIs. It's known they can cause birth defects. We're trying to model that in the worms. You can come up with a specific model of exactly what is causing the defects, and then you can come up with something -- maybe not a whole new drug, but maybe something else that could counteract it."