Chris Karlovich

Employee Spotlight

Can you tell us about your work at the Frederick National Laboratory?

Our lab, known as the Molecular Characterization Laboratory (MoCha), consists of around 45 scientists and staff members. Building 459 on Fort Detrick is our main facility, but we also have staff in three other buildings on this campus and a few based at NCI Shady Grove. We collaborate closely with NCI's Division of Cancer Treatment and Diagnosis, supporting their clinical trials. Currently, we are involved in supporting approximately 40 to 50 trials, including some large-scale ones. Our role involves receiving tumor and blood specimens and performing DNA and RNA sequencing on them. We do this both in real time and at the end of the trials.

When we perform real-time sequencing, it means our lab receives biopsy specimens from patients who are waiting for treatment. We extract DNA and RNA, prepare a “library” consisting of cancer-related DNA and RNA fragments of interest, then sequence the libraries. This entire workflow, from receiving the specimen to compiling the results into a clinical report, typically takes about two weeks. A board-certified pathologist specializing in molecular pathology reviews the report to ensure its accuracy. The report is then sent back to the treating physician, who uses this information to guide the patient's therapy based on the DNA sequence of the tumor.

When we perform sequencing at the end of clinical trials, we may handle hundreds of samples from a single trial, analyzing both tumor and blood specimens. These data help us understand why some patients respond to treatments while others do not, and why some patients experience disease progression. The insights gained from DNA sequencing are invaluable in these analyses.

In the past, before the completion of the Human Genome Project, cancer treatment was generally based on the cancer type. For example, all lung cancer patients would receive the same chemotherapy. However, our understanding of cancer has significantly improved since then. We now know that cancer is a highly heterogeneous disease. Even lung cancer has various subtypes, identifiable by specific DNA sequences. By analyzing these sequences, we can tailor treatments to target specific mutations driving the cancer's growth and progression. This approach, known as precision medicine, allows us to provide much more specific and effective treatments for patients.

How did you become interested in your line of work, and what drew you to the Frederick National Laboratory?

I've always been passionate about science, which led me to pursue a PhD. During graduate school, I studied Drosophila developmental biology, focusing on various aspects of fruit fly development. However, by the time I finished, I realized I wanted to work on something more closely related to human health. This led me to the biopharmaceutical industry, where I spent 13 years in the San Francisco Bay Area. During this time, I worked on developing drugs and diagnostics for diagnosing and treating cancer.

An exciting opportunity at the Frederick National Laboratory came to my attention through Mickey Williams, the founder of our lab and its director at the time. My wife was supportive of the move since she has family in the area. So, I decided to take the plunge and have now been here for seven and a half years.

Having lived in California my entire life, the decision to move was significant. I reached a point where I felt it was now or never. Sometimes, you just have that gut feeling that you shouldn't pass up a chance, and this was one of those times. We made the move, and it's turned out to be a wonderful decision.

What do you enjoy about working at the Frederick National Laboratory?

First, the people in the MoCha lab are fantastic. They are dedicated to our mission here at the Frederick National Laboratory and are incredibly bright. I enjoy coming to work every day because of the wonderful team we have. Additionally, our NCI colleagues are highly collaborative and excellent to work with.

An exciting aspect of our work is the implementation of cutting-edge technologies to gain new insights into cancer biology. One of my favorite technologies uses blood samples from patients with cancer to detect circulating tumor DNA (ctDNA).  CtDNA is released into the blood by tumor cells when they die. The use of ctDNA, also known as a liquid biopsy, is less invasive than traditional tumor biopsies and enables us to look for the same mutations. We have an assay that can sequence ctDNA fragments, making it a powerful tool in our research arsenal.

The sequencing machines we use are versatile and can handle various types of sequencing tasks. Whether we are sequencing tumor DNA or analyzing circulating tumor DNA from blood samples, we use the same instruments. This flexibility allows us to conduct a wide range of analyses efficiently and accurately.

Which project has been the most significant?

I believe the most significant project would be the NCI-MATCH trial. This was a massive trial conducted by the NCI over seven years and stands as the largest precision medicine study ever conducted. The trial consisted of 39 separate treatment arms, each with a different drug. We established a central network of labs to screen patients, with our lab serving as the hub. The core principle was to test tumor tissue for specific mutations that could be targeted by drugs included in the trial. This approach is known as precision medicine, and the NCI MATCH trial was NCI’s first Precision Medicine Initiative. The trial enrolled over 1,000 patients, marking a significant milestone in oncology. The successful implementation of DNA sequencing at such a large scale is something I am particularly proud of.

What accomplishments at the Frederick National Laboratory are you most proud of or how has your work made impact?

An important point I'd like to highlight is the profound impact I feel we're making on the lives of cancer patients through our work here. The sequencing data we generate are used by treating physicians to make informed treatment decisions, putting patients on therapies that are most likely to be of benefit. I often remind our team that we are genuinely making a difference.

It’s important to emphasize how much cancer treatment has evolved over the past 25 to 30 years. The advancements we have made in understanding the key events that drive cancer at a molecular level and the DNA sequencing capabilities we have today have fundamentally changed how we approach treating cancer patients.

What piece of advice has helped you in your career?

Many years ago, someone shared with me a saying attributed to Teddy Roosevelt, which resonated deeply with me. The essence of it is that before people care about how much you know, they need to know about how much you care. I’ve found this principle to be of tremendous value in both my professional and personal life. Showing you care is paramount, and I strive to always remember this.

What are some of your hobbies or special interests outside of the office?

I've always loved exercising, and it's been a part of my routine for as long as I can remember. During the week, I wake up at five in the morning to head to the gym. I might use the rowing machine, ride a bike, swim, go for a run, or hit the weights. Exercise is crucial for me; it not only keeps me physically fit but also prepares me mentally for the day ahead. Over the years, it has proven incredibly beneficial, and I prioritize it regardless of how busy I am.

Besides exercising, another passion of mine is cooking. I also enjoy spending quality time with my son, engaging in activities he loves. These activities are my top priorities outside of work.

Give us one little-known fact about you or your best-kept secret?

When I graduated from college, I wasn't entirely sure what career path to pursue. Teaching always intrigued me, so at 22, I became a high school chemistry and AP chemistry teacher, a role I held for four years. It was a valuable experience during my youth, where I learned a lot about myself and honed my teaching skills. Teaching abstract concepts, like those in chemistry, required me to create engaging visuals for my students, especially since many were visual learners.

I quickly realized the challenges of teaching, particularly with high school students, and I gained a deep admiration for educators because of it. I was fortunate to have a mentor—a fellow chemistry teacher with a Ph.D. in pharmacology. He guided me with lesson plans and demonstration ideas. Teaching prepared me for graduate school and solidified my decision to pursue further education.

It's gratifying that former students still reach out to me, even after so many years. Recently, someone from my first year of teaching contacted me through LinkedIn. It's remarkable to me how some of these connections continue to endure.