Q&A: Dr. Mitchell Hayes, KCA Trailblazer Award Winner

Dr. Mitchell Hayes received a 2024 Kidney Cancer Association Trailblazer Award in partnership with the Michael and Ina Korek Foundation for research on “Tracing the Seeds of Progression: Spatial Transcriptomic Analysis of Immunoresistant Kidney Cancer”. Dr. Hayes is a Urologic Oncology Fellow at Moffitt Cancer Center in Tampa, Florida. We spoke with Dr. Hayes about his research and the impact it could have on people with kidney cancer.

What’s the simplest way you could explain ‘spatial transcriptomics’?

Spatial transcriptomic assays allow researchers to measure gene expression across biological tissues. This can tell how cells or groups of cells are organized in two- or three-dimensional space. In cancer research, spatial transcriptomics can give us important insight into how immune and other non-cancerous cells interact with cancer cells and each other. These cell-cell interactions or neighborhood interactions can then elucidate how cancers progress and metastasize or how the body fights cancer.

What is your research project about?

Although immunotherapy is the backbone of most treatment regimens for metastatic clear cell kidney cancer, most patients will eventually develop resistance to these drugs and their disease will progress. Our project looks at surgical kidney cancer specimens from patients who have undergone immunotherapy. Evolutionarily, these residual tumors harbor features of resistance to immunotherapy, thus our aim is to characterize those unique resistance features and identify new potential biomarkers or therapeutic targets for patients who have developed resistance. Specifically, we aim to test whether the spatial relationship of genes from the epithelial-to-mesenchymal (EMT) gene set predict survival of patients who receive immunotherapy. This hypothesis was generated from a pilot project of 13 patients. The current proposal will validate those findings in the spatial transcriptomics of 50 patients, and develop novel predictive spatial gene signatures in a multi-institutional database of 491 patients.

What about your research do you think should be most exciting to patients/families?

Today, some of the most important clinical management decisions are based on a pathologist’s review of cancerous tissue slides, or a description of what the cancer looks like under the microscope. A picture is worth 1000 words, and that certainly holds true every day in the OR, lab, and clinic. The power of spatial transcriptomics is that we can use very high-dimensional data to develop simple tissue based predictive tests that can be worked back into that same clinical workflow at the time of pathology diagnosis. I think most kidney cancer patients know that over the last two decades treatment options have exploded, which has been great. But now researchers are tasked with finally delivering the promise of personalized medicine to be able to tell patients which option is best for their cancer. I think this is one step closer to making good on that promise.

What motivates you?

On the clinical side, getting patients through a good operation and seeing them at follow up is very motivating. My favorite notes to write are those that say something to effect of “the patient is doing well without evidence of disease”. At the same time, there will always be some patients who will go through a big operation and still have recurrent or progressive disease. This is probably the biggest motivation for me on the research side. Advanced technologies and therapies like surgical robots, lasers, new ablative energies, targeted therapies, cell therapies, transplantation have made incredible advances, but only the science of patient selection can improve the balance of under/overtreatment. Another big motivation for me on the research side is the opportunity to work with career scientists who dare to ask fundamental basic science questions that challenge the assumptions we make every day in clinic.

What else do you want others to know about you or your research?

It takes a massive Team Science approach to produce this work. At every stage of the project, we have a seasoned expert scientist or clinician who is insightful and adaptive. As a fellow/trainee, I feel incredibly honored to work with these researchers who continue to teach me about how to be a better scientist. I also cannot thank my personal mentor, Dr. Brandon Manley, enough for his seemingly endless generosity and support.

We are very grateful to the KCA for highlighting and supporting our proposal. I am very excited to continue our work together and make an impact in our patients’ lives.