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Faculty Profile: Joshua Meeks, ’05 MD, ’03 PhD, ’06, ’11 GME

Sadiya Khan

Joshua Meeks, ’05 MD, ’03 PhD, ’06, ’11 GME, is an assistant professor of Urology and of Biochemistry and Molecular Genetics. At Northwestern Memorial Hospital, Meeks is an urologic surgeon, specializing in the diagnosis, treatment and management of bladder cancer. His laboratory focuses on both the epigenetics and genetic mutations associated with cancer biology with the hope of developing novel systemic and intravesical therapies to improve patient survival. Watch a video about his lab.

Meeks is also section chief of Robotic Surgery at the Jesse Brown VA Medical Center in Chicago and is a member of multiple centers and institutes at Northwestern, including the Center for Genetic Medicine, the Simpson Querrey Institute for Epigenetics, the Northwestern University Clinical and Translational Sciences (NUCATS) Institute and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. He has authored more than 100 peer reviewed publications and currently leads a handful of active clinical trials for bladd

What are your research interests? 

My laboratory is focused on bladder cancer. As a urologic oncologist, we are able to see this very aggressive cancer from a different perspective and I see patients approximately 50 percent of my time at Northwestern.

We focus on three main problems. The first is trying to treat bladder cancers that are resistant to conventional therapies, such as immunotherapy and chemotherapy. We think that leveraging some of the unique mutations that occur in bladder cancer makes them particularly susceptible to therapy targeting DNA and chromatin. These would be considered epigenetic therapies. A second major focus of our laboratory is trying to identify more “at-risk” patients that should be treated with either more aggressive therapies at an earlier stage or different precision therapies. Last, there is a significant sexual dimorphism in bladder cancer where men are diagnosed approximately three to four times more than women, but women have significantly worse outcomes. We think there’s a very strong biologic driver here that likely involves a tumor in the immune microenvironment. Our lab uses techniques that include mice, cells tissues from patients and different organoid systems.

What is the ultimate goal of your research?

The ultimate goal of our research would be to cure bladder cancer, or rather identify the real cause of bladder cancer. I truly think it’s a preventable cancer. Interestingly, there’s been no survival improvements in bladder cancer in over 40 years. Survival is still at a median of 14 months for patients with metastasis. This is the second lowest of solid tumors. I really think bladder cancer is too heterogenous for a “one size fits all” approach, which emphasizes the role of biomarkers and molecular subtyping. Bladder cancer is considered a disease that occurs secondary to smoking, but only half of our patients are actually smokers. One thing that we study is how carcinogens cause bladder cancer. As a surgeon that works at the VA, I see many patients that were exposed to carcinogens during chemical and biological warfare.

How did you become interested in this area of research?

I became interested in bladder cancer and tumor genomics as a fellow in oncology at Memorial Sloan-Kettering Cancer Center. Bladder cancer was really a black box with very limited therapies, yet it seemed very interesting to me at the genetic level. It was clear to me that my colleagues would make significant improvements in the survival of patients with prostate and renal cancer. Testicular cancer was essentially cured with platinum chemotherapy, but bladder cancer remains a challenge.

Bladder cancer looks like lung cancer, or melanoma. Survival is terrible for patients with metastasis. As a surgeon, we have constant access to the bladder and this readily prepares us for trials, biomarkers and interventions, and we just hit things at the right time — coming to Northwestern at the beginning of The Cancer Genome Atlas (TCGA). I collected tumors for the TCGA as a fellow and by the time I finished my fellowship, the bladder TCGA was published.

Almost 70 percent of bladder cancers have a mutation in chromatin regulatory proteins. I learned a lot from Ali Shilatifard — he cloned the proteins that we see mutated in bladder cancer. The first immunotherapy trial was opened at Memorial Sloan Kettering when I was a fellow. I thought that bladder cancer made a lot of sense to look at as “immunoresponsive,” since we used tuberculosis as a common treatment. I wrote a phase I trial when I arrived at Northwestern that we just completed. Again, lucky to have great mentors at the right time. 

What types of collaborations are you engaged in across campus (and beyond)? 

I’ve been so fortunate to have amazing colleagues that I learn from daily at Northwestern. I’ve been at Northwestern for over 20 years, so our lab has friends and collaborators across many departments.

I have an appointment in Biochemistry, and Ali Shilatifard has been a great collaborator and mentor. We meet monthly officially, but I have frequent touch points. I have a close relationship with Steve Miller in Immunology. He’s taught me so much about immunology. I was recruited by Tony Schaeffer to become a urologist, and his son, Ted Schaeffer, is my chair. Ted has been so supportive, and one of the rare urologists that is a surgeon-scientist. Ted will call at five or six in the morning and what he accomplishes daily motivates me.

Our genitourinary medical oncologists are amazing, and I really enjoy every interaction I get to have with them. They’ve taught me a great deal about clinical trials, but we are quite fortunate to have collaborators in both urology and biochemistry. We have strong collaborators outside of Northwestern at Johns Hopkins, University of Texas, San Antonio, and in Vancouver, Denmark, Brazil and Paris. Slack has been great to constantly share information and data across the world.

How is your research funded?

We have been very fortunate to have funding from multiple sources since the lab began. The VA has been very supportive of our research. I had a Merit Award, funded in 2016, that was just renewed for six years. We have funding from multiple grants from the Department of Defense and the Prostate Cancer Foundation. Robert F. Smith, the philanthropist, funded our precision oncology center at Jesse Brown VA. Recently, we were funded by the Polsky Institute to study gender disparities in bladder cancer. I’d really like to be funded by the National Cancer Institute and am currently working towards this goal.

Where has your work been published?

We had a paper published in European Urology, which is the best journal in our field right now, that describes the heterogeneity of stage I tumors. These tumors were a real enigma. This was a problem we have been addressing for five years — most patients do quite well with stage I tumors with the intracavitary tuberculosis vaccine (BCG), but about 15 percent will have progression and death. The patient has to decide about bladder removal or BCG therapy. This leads to a lot of over and under treatment. Our transcriptome analysis found that tumors can respond or not respond to BCG for many reasons. We actually found five different tumor subtypes using unsupervised clustering. One of these subtypes seems to have a strong epigenetic imbalance that could be targeted with a specific small molecule. The exciting thing was to develop a classifier that we could potentially use to help patients make decisions about treatments.