Q&A: Dr. Syed Muneeb Alam, 2026 KCA Grant Winner
Dr. Syed Muneeb Alam received the 2026 KCA Interdisciplinary Medicine Focus Award given in partnership with the Michael and Ina Korek Foundation. Dr. Alam’s research investigates the “Impact of Obesity and the GLP-1 Axis on Anti-Tumor Immunity in RCC”. Dr. Alam is an Assistant Professor of Urology at the Yale School of Medicine. We spoke with him about his research and the impact it can have on people with kidney cancer.
Describe your project and how you developed the idea.
Obesity is an established risk factor for renal cell carcinoma (RCC), and it is estimated that over half of patients with RCC are obese. Given the rapidly growing using of medications targeting the glucagon-like peptide 1 receptor (GLP-1R) for the treatment of diabetes and obesity, a significant portion of patients with RCC are now on these agents. Unfortunately, very little is known about the impact of these agents on cancer biology, and it is hypothesized that drugs targeting GLP-1R can potentially impact tumor behavior and treatment response.
Based on preliminary data from our group and others, many cells found within an RCC tumor express GLP-1R and therefore may be affected by these medications. In other types of cancers, expression of GLP-1R has been associated with markers of response to immunotherapy, which remains the backbone of standard treatment for many patients with RCC. GLP-1R has also been associated with immune cell exhaustion, raising the concern that use of GLP-1R medications can potentially impact response to immunotherapy.
This project is part of a broader effort to understand the influence of obesity on immune cell function in kidney cancer, with a focus on understanding how targeting GLP-1R could affect anti-tumor immunity. The first aim of this project will use a large cohort of RCC tumors that underwent single-cell RNA sequencing (which allows us to understand gene expression by individual cells within an RCC tumor) to understand the influence of GLP-1R expression on immune cell characteristics. In the second aim, we will expose T cells (a type of immune cell) derived from patients with kidney cancer with drugs that either activate or block GLP-1R to understand how these medications may impact T cell function, which is critical to the activity of immunotherapy.
GLP-1 agents have become more widely known recently in relation to weight loss, but how long has this pathway been a focus of study in RCC or cancer?
The use of agents targeting GLP-1R has skyrocketed over the past several years, outpacing our understanding of how these agents impact cancer biology. Most studies evaluating GLP-1 in kidney cancer have used large population databases to determine if the use of GLP-1R medications is associated with an increased risk for kidney cancer. These studies have produced mixed results, and biological pathways involving GLP-1 are poorly understood in the context of RCC. In other cancer types, the GLP-1 axis appears to influence T-cell exhaustion and may affect other key immune cells such as natural killer (NK) cells. The GLP-1 axis may also affect release of cytokines, which are signaling molecules that can both activate or suppress the immune system depending on which cytokine is released and in what context.
In a study of colorectal cancer cells, inhibiting GLP-1R (the opposite of what obesity medications do) was shown to slow cancer growth in the laboratory, a finding that raises the question of whether GLP-1R could be a potential drug target. Based on existing data and the continued increase in use of medications targeting GLP-1R, it is critical to understand how these agents may impact tumor biology – specifically, immune cell biology – in patients with kidney cancer.
What is the most exciting thing about your research for patients and families?
The purpose of this project is to improve our understanding of how medications targeting GLP-1R potentially affect clinical outcomes in patients with kidney cancer. I think the most exciting aspect is the possibility of direct translation, in which biological insights gained through this project have the potential to inform future clinical decisions that can improve quality of life and outcomes for patients with kidney cancer. My ultimate hope is that the results of this project will help to inform the design of clinical studies seeking to optimize the use of GLP-1R agents in patients with kidney cancer. As the number of and indications for these medications grow, I hope that studies such as these will help to guide patients who may be on or considering taking an agent targeting GLP-1R during their treatment for kidney cancer. I am personally excited by the prospect that inhibition of GLP-1R may in fact favorably modulate immune cell activity, a finding which would raise the possibility of a new cancer drug target worth studying further.
What motivates you?
As a surgeon-scientist, I am most motivated by the patients that I care for on a regular basis. My research program is designed to address the fundamental challenges faced by patients with kidney cancer and their families, and the personal relationships I develop in the clinic are the strongest motivator for my work as a scientist. It is a privilege and immensely gratifying to be able to address unanswered clinical questions through lab-based science. In addition to my patients, I continue to be motivated by my colleagues, lab members, and mentors who all continue to teach me daily.
What else do you want others to know about you or your research?
The long-term goal of my research is to translate biological insights into impactful clinical trials. While it is important to fill ongoing knowledge gaps in kidney cancer, I think it is essential to bridge this knowledge with clinical care. I hope to continue designing lab-based research studies that are clinically applicable and that directly account for patient priorities.