Meet the Researchers: Jes Sanders

Jes Sanders is a fifth-year general surgery resident at Northwestern Memorial Hospital and a postdoctoral research fellow in the laboratory of SQI members James Mathew and Joseph Leventhal. He recently presented a Rising Stars of SQI Lecture titled “Leveraging Antigen-Specific Regulatory T Cells as Adoptive Cell Therapy in Organ Transplantation.” In this interview, Sanders summarizes his lecture topic and explains why he was drawn to the field of transplant immunology.

How would you summarize your Rising Stars Lecture topic?

I’ve been working with Dr. Leventhal and Dr. Mathew for the last two years, and they are two of the world leaders in an area known as transplant tolerance. In organ transplant recipients, currently the way we prevent rejection of new organs is by giving patients immunosuppressant medications for their entire lives.

Dr. Mathew and Dr. Leventhal have dedicated their research to finding ways to manipulate the recipient’s immune system so it recognizes the new organ as “itself.” The idea is that rather than attacking the organ and causing rejection, the recipient’s immune system will actually protect it.

One of the ways we’ve been trying to achieve this is using a particular kind of white blood cell called a regulatory T cell. Unlike some other kinds of T cells, these cells are very important for maintaining the balance of the immune system.

For my project, we’ve been expanding these cells in the lab and “educating” them, teaching them how to be more targeted and effective in response to the new organ. There’s quite a bit of manipulation that occurs in the lab, but everything we’ve done so far indicates that the Tregs we’re growing are effective in downregulating the recipient’s immune response toward cells from the donor.

The next steps are to fully translate this from the lab to the clinic. Right now, we are in the final stages of the initial product development before starting our clinical trial.

What types of techniques do you use to “educate” these cells, multiply them in the lab, and then administer them to patients?

From start to end, the whole process takes about six weeks. To start, we use cells from the person who is going to donate the organ, and we co-culture them with the recipient’s cells. Over the course of a couple of weeks, there is a natural selection process that takes place. The recipient cells that can recognize the donor cells get a signal to survive and keep proliferating, so we are able to select those cells out from all the other ones.

We then expand the cells using a variety of strategies in order to ensure we have enough cells to give to the patient. We plan to give this as a single IV infusion about two and a half months after transplant. The reason we wait this long is because we want to make sure the effects of the immunosuppression that we give patients at the time of transplant have worn off before we give our therapy. Otherwise, those immunosuppressants would wipe out the cells that we’re giving them.

Can you go into more detail about the problem the cell therapy you are working on would solve? How big of an issue are the immunosuppressants that patients are currently taking?

These medications are expensive and have a lot of side effects. Our patients can develop high blood pressure, injury to their kidneys, or diabetes, and some patients are unable to tolerate the medications due to side effects, which is unfortunate because they must be on them to protect their new organ.

To be honest, I don’t think the therapy that we’re developing now is going to be the end-all, be-all. We still have a lot of work to do, but what we hope to achieve is to limit the number of medications that each patient must take. In general, people are either on two or three medications; if we could get them down to one, that would be huge.

That’s not only going to decrease the number of side effects, but it’s going to help patients be more compliant with taking their medication.

How did you get connected with Drs. Mathew and Leventhal and decide to pursue this line of research?

I got interested in immunology almost 10 years ago. Right before I came to medical school at Northwestern, I was diagnosed with ulcerative colitis, which is an autoimmune disease. Since then, I’ve been on a biologic therapy and get an infusion every couple of months.

In medical school, I worked with Dr. Josh Wechsler, a pediatric gastroenterologist, studying pediatric ulcerative colitis. Once I started residency, I knew I wanted to do something in the field of immunology during my protected research time.

How I got linked in with Dr. Mathew and Dr. Leventhal was sort of serendipitous. Dr. Karen Ho, who is our Director of Resident Research for the surgical residency, introduced me to Dr. Mathew. A spot had opened up in the lab, so I met with him and talked through what they do and it felt like the perfect fit.

Do you see yourself continuing as a surgeon-scientist, or do you think you’ll focus more strongly on one area as your career progresses?

Hopefully it will work out that I can be a surgeon-scientist. I want to be an abdominal transplant surgeon, so once I finish up in the lab three months from now, I still have four years left until I’m completely done with training. But my experience over the last two years has really shown me what area of transplant science and transplant immunology I want to be involved in. 

I’ve been very fortunate to be at Northwestern and have the infrastructure to allow me to learn all these techniques in the lab, how to apply for grants and write manuscripts, and everything else I would need to have a career as a surgeon-scientist.

What are your hobbies outside of your research and surgical training?

I enjoy running, cycling, and lifting weights. Even when I was in clinical training, I worked out five or six times a week. It’s really important to me and how I destress after a long day.

I’ve also been playing golf since I was two and a half. It’s something that both my sister and I did growing up. Anytime I get together with my family, the first thing we do is go out and play a round of golf together. It’s been more difficult being in Chicago as opposed to my home state of Arkansas, because it’s cold here during the winter and it’s hard to get out to a course that isn’t close to downtown. But even so, I’ve still had the chance to play with some of my coworkers.

Are there any other projects you have worked on during your two-year research period?

One of the other projects I’ve been working on with Dr. Mathew and Dr. Leventhal is developing a unique biomarker for rejection in kidney transplant patients. It’s a complicated process but it uses sequencing of T cell receptors, and we can identify those before transplant and then track them post-transplant. It can give us an early idea of whether a patient is about to reject the new organ if we see more of these cells popping up post-transplant.

I’ve also worked with one of our other surgeons, Dr. Daniel Borja-Cacho, who studies machine perfusion in transplantation. Once an organ is taken out of the donor, it’s subjected to a variety of insults before it goes into the recipient — it’s being put into a cooler with ice, it’s not getting blood flow, it’s not getting the oxygen and nutrients it needs. By using a perfusion device, we can minimize these insults before it goes into the recipient.

I’ve been studying that in the context of liver transplantation, and our patients who have received organs that have been perfused with our pump are doing really well.