From Telomeres in Space, Cancer Research to Microbes on Earth: Harnessing the Power of qPCR

Conversation with Dr. Christopher Mason from Weill Cornell Medicine

From cancer research to space medicine, Dr. Christopher Mason’s work spans an impressive range of applications. As a professor at Weill Cornell Medicine, he focuses on clinical genetics, computational biology, and synthetic biology to improve diagnostics, develop analytical tools, and design cells, genomes, and microbiomes.

Our Senior Manager for Global Market Development in Genetic Sciences, Dr. Vishwadeepak Tripathi, interviewed Dr. Mason to learn more about how he uses techniques like quantitative PCR (qPCR) and sequencing. Their discussion covers everything from biomarker validation and microbiome analysis to integrating automation in research workflows.

Q: How do you typically use qPCR in your research, particularly in microbiome and cancer studies? Are there advantages of qPCR over sequencing?

A: We use qPCR for a wide range of applications. In cancer research, we use it to detect and validate copy number and structural variations in tumor genomes. In space medicine, we use it to study how radiation impacts astronauts’ genomes, such as changes in telomere length or mutations.

We also do a lot of sequencing, but whenever we see an interesting mutation, we validate it with an orthogonal assay like qPCR. Due to its high sensitivity, qPCR is our preferred validation method for cancer gene expression studies and microbiome research.

Q: How do you use qPCR to validate cancer biomarkers identified through RNA-seq?

A: We use RNA sequencing extensively, including shotgun RNA-seq, single-cell sequencing, and spatial transcriptomics for biopsies. However, qPCR is the most sensitive method we use to validate gene fusion events, expression changes, or isoform variations.

I’ve shared my thoughts in publications saying that there are no unambiguous gold standards, and that each technology has its limitations, but I still consider qPCR the high bar for validation.

Q: What role does qPCR play in cancer research, particularly in identifying oncogenes, tumor suppressor genes, or cancer-related biomarkers?

A: qPCR is really effective in cancer research. It can identify novel rearrangements and genotype changes in oncogenes or tumor suppressor genes, including genes like p53, which act as the guardian of the genome. qPCR is a way to clarify which mutations are present and what rearrangements have occurred in the genome; it is a very sensitive method for doing so.

Q: What factors do you consider when choosing reference genes for qPCR in cancer tissues, given the variability in gene expression between tumor and normal cells?

A: Selecting control genes for qPCR has always been a challenge. Historically, housekeeping genes were assumed to have stable expression across tissues. But, research has shown that even these genes can vary depending on tissue type, disease state, or stress conditions. So, we typically use multiple reference genes like GAPDH or ribosomal genes and include both biological and technical replicates.

Q: How do you apply qPCR to study minimal residual disease (MRD) and monitor cancer recurrence?

A: One really exciting application of qPCR is in monitoring MRD. It allows us to track mutations like EGFR in a patient’s blood after therapy. For instance, mutation levels may decrease during treatment but could later re-emerge. qPCR, with its high sensitivity, will fundamentally change how we look at cancer. We will not just treat your cancer; we’ll monitor it, look for variations of it, and search for new mutations that arise. So, it’s really an exciting time for MRD because we can finally see the cancer evolve at this high resolution with panels and NGS, then focused tracking with qPCR, and then use that to guide therapy. We’re very excited about that application.

Q: Between qPCR and digital PCR, which do you prefer for MRD studies?

A: We’ve used both qPCR and digital PCR for MRD. The choice depends on validated panels and known targets. qPCR is favored for its long-standing reliability and general robustness while digital PCR is effective for detecting rarer targets. Currently, there’s a debate in the field regarding the preferred method. Some primers and probes have proven to be highly reliable and well-validated, particularly those used in qPCR, since they have been in use for a longer duration.

Q: How do you combine qPCR with other methods, such as 16S rRNA sequencing, to gain deeper insights into the microbiome?

A: We often use qPCR complementary to sequencing to study the microbiome, especially in samples with a high host DNA background, such as skin or coral. For example, in skin samples, 99% of DNA could be human, making it challenging to isolate microbial DNA. Methods like 16S rRNA amplification are effective in identifying microbial profiles by overcoming this background noise. When we use qPCR and sequencing to confirm each other, we gain a clearer understanding of the microbial ecosystem, whether it’s skin, gut, or coral microbiomes.

Q: What emerging applications of qPCR in microbiome research do you find most promising and why?

A: One of the exciting applications of qPCR in microbiome research is tracking antimicrobial resistance in wastewater. We can now see how resistance spikes over time and even correlate these spikes with antibiotic prescriptions at a hospital. We recently published a paper showing that qPCR can detect resistance genes or even pathogens like monkeypox down to just a few copies per liter of wastewater—sometimes before they are observed in the patient population. This ability to profile wastewater at such a deep level provides a window into the epidemiology and virology of a community, or even an entire country. What’s particularly exciting is that we don’t have to rely on individuals reporting symptoms; we can detect potential outbreaks before people even know they’re sick.

Q: Do you still use Sanger sequencing in your workflows?

A: Sanger sequencing is thought of as a technique from the 80s or 90s But I still think it’s a great tool for validation. One area where we still see Sanger sequencing being used is in validating complex rearrangements or when identifying a new target, such as in consortium projects or when filling gaps in a new assembly of the human genome.

However, in my lab, we don’t actively use Sanger sequencing anymore. We haven’t had it in our workflows for years, but it remains a valuable method in specific contexts.

Q: What advice do you have for young scientists who want to follow a similar career path?

A: Stay curious. Keep asking questions until you reach a point where no one has the answer—that’s where the real fun begins. Those unanswered questions are your opportunities to discover something new. You can then start to piece them together, creatively. For example, using bacterial CRISPR for therapeutic development or borrowing a gene from a tardigrade to enhance radiation resistance in human cells. The possibilities are endless. Biology is like a massive playground of information, and we now have the tools to explore and build within it.

Q: You’re a busy and accomplished scientist. What do you do in your free time? What are your hobbies?

A: I have a lot of hobbies. I love running, and I just ran the New York City Marathon and Half-Marathons. I also enjoy spending time with my family and taking French lessons, though I’m still working on becoming fluent. Beyond that, I love traveling and learning about other cultures, always keeping an open mind and curiosity about different places in this world.

Q: As a scientist, what is the most mysterious question you would like to find answers for?

A: There are several big unanswered questions in science. One of the most intriguing is: where did life first originate? Was it here on Earth, or could it have started on other planets? Could we find life in the clouds of Venus or deep in the bedrock of Mars? And if there isn’t, should we go put it there?

And another huge question for me is: how long can life survive? Could humanity make it beyond our solar system and reach other star systems? I believe we can, but it will require will and careful planning. Ultimately, the question is how far we can go as a species and as shepherds of life.

Q: We hear you’ve written a book. Could you tell us what it’s about and what readers can gain from it?

A: The book is called The Next 500 Years: Engineering Life to Reach New Worlds. I wrote it as a blueprint for what humanity can and should strive to achieve over the next 500 years. It’s about setting intergenerational goals—specifically, how we can extend life to other planets and ensure its survival.

I discuss why it’s important for us to take on this responsibility. We are the only species that understands extinction, and with that understanding comes a duty to preserve life—not just on Earth but across multiple planets. The book is a combination of philosophy, ethics, and technology, exploring what we can achieve as caretakers or shepherds of life in the universe. Learn more about the book The Next 500 Years.

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