After losing three grandparents to cancer and taking a close look at intestinal diseases, Postdoctoral Fellow Alican Ozkan is determined to find better therapeutic options for all patients, regardless of race, ethnicity, age, or sex
By Jessica Leff
On the banks of the Aegean Sea sits Izmir, the third-most-populous city in Turkey. It’s geographically part of Asia, but culturally seems more at home in Europe. This is also the city where Alican Ozkan grew up.
His parents, both chemical engineers, met at their university. They soon discovered they had the same hometown and took a shuttle back together at least once a month. This proved convenient once they were married, since both of their parents lived in Nazilli, about an hour drive from Izmir.
When Alican was born, his mother was still pursuing her Ph.D. He spent a lot of time, including summers and winter breaks, with his doting grandparents while she worked on her dissertation. “Summers would be spent swimming, cycling, and cooking,” he remembers. “My parents were really into cooking traditional Turkish dishes and still I try to keep up cooking family recipes.”
From dreams of F1 race engineering to dreams of Organ Chips
By the time Alican was in high school, he knew he wanted to be an engineer based on his interest in physics and math. He also had a passion for both Formula One and MotoGP racing, following along on television. “Formula One is probably one of the few sports that relies heavily on engineering, rather than just the skills of the driver,” he explains.
So, Alican decided to study mechanical engineering with the hopes of becoming a race engineer, a professional responsible for managing the racecar. He even had an internship at a company collaborating with Formula One teams.
Formula One race engineering is an incredibly selective career, and as the sport evolved to meet sustainability goals and implemented cost caps, the amount of people on a team’s staff reduced. Alican eventually decided he would rather use his skills for something more attainable – and arguably more important: microfluidic systems for biomedical applications.
“There are a lot of uses for mechanical engineering in healthcare,” Alican says. “Biology becomes more enjoyable to me once it is more quantitative and applied, and it’s really attractive in terms of the usefulness of the technology.”
When your family becomes the face of your research
In 2015, Alican traveled over 6,500 miles to Austin, Texas to pursue his Ph.D. He developed novel Organ Chips to study tissue stiffening, and looked at how this would moderate the function of endothelial barriers, which control the nutrient transport in and out of different organs, and treatment efficacy in cancer cells. He modeled metastatic breast cancer and hepatocellular carcinoma (HCC), otherwise known as liver cancer.
After developing a model of HCC, during the second part of his Ph.D., Alican collaborated with a clinician at the MD Anderson Cancer Center to simulate drug delivery methods in Organ Chips. It was at this time he received some devastating news: his father’s mother was diagnosed with HCC.
Because of his work, he saw the writing on the wall. He remembers, “I already knew that the survival rates were pretty low. It’s basically a death sentence. HCC treatment is particularly challenging, because it’s mostly diagnosed in an advanced stage where the tumor is in a critical organ, so the chemo-associated side effects are strong and system toxicity is high.”
After nine months his grandmother unfortunately passed away from liver cancer.
Years later, Alican only has one remaining grandparent: his mother’s mother. He explains, “Almost every time I visit my last grandmother, I see this nice picture from my first birthday where all four of my grandparents were with me. Now, because of cancer, there’s only one left.” In addition to the grandmother who had liver cancer, he lost both of his grandfathers to prostate cancer.
From Austin to Boston, from the liver to the intestine
In June 2020, in the midst of the COVID-19 pandemic, Alican and his wife drove from Texas to Boston, Massachusetts, so he could begin his postdoctoral fellowship at the Wyss Institute. Here, his work is focused on modeling intestinal diseases and addressing challenges associated with them.
Inflammatory bowel disease (IBD), the umbrella term encompassing Crohn’s disease and the related inflammatory disorder ulcerative colitis, which is often called by ulcers in the intestinal wall, is incredibly disruptive to people’s lives. Alican explains, “Imagine an adult patient having to wear diapers all the time or check where the restroom is wherever they go. If an athlete gets diagnosed with IBD, they often have to retire because the disease causes serious fatigue. There is also a greater risk for female patients as it puts a person at high risk for maternal health issues.” Even worse, if these conditions aren’t well managed, they can lead to more serious complications, like colorectal cancer.
Currently, many patients develop resistance to treatment in a short amount of time or don’t respond well to available therapeutics. Mostly, immunosuppressants are used to target the immune system in the gut’s epithelial lining.
Alican and his colleagues are modeling IBD in Organ Chips and researching how the different forms of the disease trigger specific complications.
Their second project relates back to cancer: they’re looking at drug- or microbiome-related countermeasures against radiation-induced intestinal injuries. Radiotherapy, while helpful against cancer, can cause diarrhea and serious digestive problems because it does not only target the tumor, but also the surrounding organs. This work has become personally relevant again, as Alican’s grandmother-in-law was diagnosed with colorectal cancer.
Reimagining more personalized medicine
After studying various cancers and intestinal diseases, Alican has a good idea of what he’d like to see in the future. He says, “If I could Reimagine the World, it would be one with more personalized treatment options available to all patients, regardless of race, ethnicity, age, or sex.”
Alican’s vision is inspired by what he has learned about IBD patients. Female patients receiving TNF (tumor necrosis factor) inhibitors, or other anti-inflammatory drugs, to manage their IBD have more severe symptoms than male patients. This has been correlated with the fluctuation in their hormones corresponding to their menstrual cycle. Female IBD patients are also often advised to wait until their disease is in remission before they attempt to become pregnant, because IBD can cause severe complications when carrying a child.
In addition, most clinical trials for IBD treatments have been done in white patients, rather than an equal distribution across races and ethnicities. It has also been found that IBD varies in how exactly and frequently it occurs in different ethnic populations, but the reasons have not been explained yet. Alican laments, “We still don’t know too much about how we can propose treatments for male versus female patients or white versus African American patients.”
In an effort to realize his vision, Alican and his colleagues plan to use Organ Chips to further understand how female patients are affected differently by IBD in relation to their menstrual cycles or pregnancy hormones. They recognize that the first step to solving a problem is admitting you have one. “Our work doesn’t always need to be finding an immediate solution, we can start by bringing light to the fact that there is something that deserves a closer look, or discovering something that has not been well-documented.”
Though Alican hasn’t become a Formula One race engineer, he’s happy to have the opportunity to change people’s lives. He explains, “The translational potential is pretty attractive and makes the work more enjoyable.”
And despite his personal losses, Alican feels fortunate on the family front as well. “I consider myself lucky because some people don’t even get a chance to meet their grandparents. I had the chance to spend good time and make lasting memories with mine.”