Systems Biology and Women's Health: A Q+A with Tal Korem, PhD

As a member of Columbia University’s Program for Mathematical Genomics (PMG) , Tal Korem, PhD, is bringing his interests in systems biology, quantitative research, and the human microbiome to areas of clinical relevance. For Dr. Korem, that clinical focus is women’s reproductive health. 

“There is still a lot we don’t understand that relates to women’s health, to fertility, and to birth outcomes, and how microbes play a role in all of this,” says Dr. Korem, assistant professor of systems biology, with a joint appointment in obstetrics and gynecology at Columbia University Vagelos College of Physicians and Surgeons. A current focus of the Korem lab is preterm birth, i.e., birth that occurs prior to 37 weeks of gestation, though Dr. Korem intends to expand into other areas such as infertility and endometriosis. 

Tal Korem, PhD
Tal Korem, PhD

Dr. Korem’s interest in  women’s health research is personal, stemming from several impactful experiences that hit close to home. 

“My aunt passed away from ovarian cancer and I have seen friends and family members struggle with idiopathic infertility,” he says. “Also, witnessing the complications with the birth of my first child, which involved emergency procedures, motivated my interest in this area, and I am very excited about the potential to contribute to women’s health with my own research.” 

Dr. Korem, a native of Tel Aviv, Israel, is the first in his family to earn a PhD, and had entered academia as a medical student. After completing  his undergraduate degree, he enrolled in a MD/PhD graduate program. There, he realized that research was what he enjoyed the most. He is a trained computational biologist, and studied under Professor Eran Segal at the Weizmann Institute of Science, where his work focused on the  human microbiome, a complex system of microbial communities that inhabit every body part. 

In the last two decades the gut microbiome, in particular, has attracted a lot of research interest for its strong associations to human health and disease. Researchers in the Korem lab are using novel computational methods to study how different microbes combine their metabolic activities to produce metabolites that have a systemic effect on the host. 

"The Program for Mathematical Genomics gives me the opportunity to conduct research in a place that does strong quantitative work … and at the same time, be very connected to the clinical side.”

The Korem lab is now applying these methods to study cancer. Specifically, working with a global team of researchers, Dr. Korem is helping to develop a comprehensive computational framework that will identify microbial high-risk factors for pancreatic cancer.  Funding for this research is provided by a grant from the Pancreatic Cancer Collective (PCC), awarded in the spring of 2018 and co-led by PMG Director Dr. Raul Rabadan .  “We hope that the results of this work will enable better and earlier identification of individuals at risk for this lethal disease, facilitating improved treatment and prognosis.”

This academic year marks Dr. Korem’s one-year anniversary as both a Columbia faculty member and first-time New Yorker. Prior to joining Columbia, he was a postdoc and graduate student at Weizmann, earning his PhD in computational biology, and at Tel Aviv University from where he received his Bsc. in medicine. In September 2019, he was named a CIFAR Azrieli Global Scholar in the Humans & the Microbiome program by CIFAR, a Canadian-based global charitable organization that targets pressing questions in science and technology. The fellowship will support Dr. Korem’s work in microbiome metabolism. CIFAR’s community of fellows includes 19 Nobel laureates and more than 400 researchers from 22 countries. 

Q: Tell us what fascinates you about studying the human microbiome and a bit about your focus in this area.

A: For the past couple of decades, we’ve been finding statistical associations between the microbiome and probably every disease you can think of. Like patients with electronic health records, we have come to think of the microbiome as sort of our biological health record. It is like a one-stop-shop for indications about almost everything that’s wrong with a person. It’s also a system that’s very challenging to explore. With genetics studies for example, there is an expected way in which things progress. If I’m now finding a new mutation that has a very strong signal for some disease, then it probably means that the mutation affects the disease in some way, whether directly or indirectly. 

With the microbiome, it is probably the opposite direction that is more reasonable, and that’s why we’ve been able to find all these associations of these signatures to changes in the microbiome. This means that whenever something is changing with the physiology of the host or when we get a disease or a condition, they cause a change in the microbiome. There is also a lot of evidence that there are some effects the other way around – and trying to find the microbiome’s causal effects on disease is the most interesting challenge for me and my lab. While the host affecting the microbiome gives us diagnostic understanding, the microbiome affecting the host, we hope, will lead us to novel therapeutics. 

Q: Are you oftentimes considering a clinical application in your research? 

A: We are always working on two things at the same time—one is our methodological or analytical approach to a research problem and the other is thinking about a specific clinical area. When we’re working on a new computational approach, where we can apply it is at the top of our minds. 

Q: A majority of your research is in women’s health. What are you currently working on?  

A: Right now our major focus is in preterm birth, and studying the link between the vaginal microbiome to this condition. It has been observed that there is a direct involvement of the vaginal microbiome in an estimated 25-40% of preterm births. But, we don’t yet know enough about the link. One hypothesis is that ascending infection from the vaginal or cervical area to the uterus triggers preterm birth in some cases. Scientists have also looked at metabolic effects associated with this condition. Despite these strong links between the vaginal microbiome and preterm birth, we don’t yet have good biomarkers of preterm birth and it is still hard to know whether a woman carrying a child will have this condition. Known risk factors are not predictive enough. If we can sample the vaginal microbiome in the first trimester and use it to mark really high risk women, then this could change the way this condition is treated. 

There are many research groups looking into this problem. The challenge is that it likely does not link back to a single microbe but, rather, to how the microbial ecosystem works as a whole. For example, we see that microbes associated with preterm birth are different from cohort to cohort and across different ethnicities. We are aiming to identify the underlying principle that connects all of this together—a mechanism that explains why some women experience preterm birth, or how we can use this mechanism to make an early diagnosis. Our work is focused on analyzing the data, developing machine learning approaches tailored to this type of data and to various characteristics of the data, and applying different approaches that could produce better predictors than what we currently have. 

Q: You are faculty of the Program for Mathematical Genomics (PMG), a multidisciplinary center born out of the Department of Systems Biology in the fall of 2017. What drew you to PMG? 

A: When I was searching for a position, I was looking for a quantitative program or department but I also wanted to be across the street from a hospital. Right now, I’m in a hospital, and that’s even better. PMG gives me the opportunity to conduct research in a place that does strong quantitative work, to be able to collaborate with people like Raul [Rabadan] and at the same time, be very connected to the clinical side. There aren’t a lot of institutions that can provide both.

Q: You first studied to be a doctor. What changed your mind? 

A: When I joined an MD/PhD program, I thought a PhD would be a nice addition on my way to becoming a doctor. But once I started, I realized that research really is the place for me, and decided not to go back to medical school and complete my MD. Every once in a while I wonder if I should have completed my MD, for various reasons; but ultimately I knew I wanted to be on the cutting edge of medicine, where medicine isn’t working or where you don’t yet know what is going on. I think that is exactly where I am today, and where my research is. Research in the microbiome area is very challenging and interesting from a quantitative standpoint, and at the same time could probably lead down the road to better, improved medical advances. 

-Melanie A. Farmer