Q&A: Dr. Katherine Alexander, 2025 KCA Grant Winner

Dr. Katherine Alexander is a researcher, Assistant Professor, and Cancer Center Member at Cold Spring Harbor Laboratory, a biomedical research and education institution in New York. Dr. Alexander received a 2025 KCA Research Award for a project on “Nuclear Speckles as Prognostic and Predictive Indicators in ccRCC”. We spoke with Dr. Alexander about her work and what it might mean for patients.

What are nuclear speckles? And how are they related to kidney (or any) cancer?

Although we consider the nucleus of the cell as the container for our DNA, the nucleus is more than just DNA. Different types of non-DNA structures coexist within the nucleus, intermingling with the DNA and impacting its interpretation. One such structure is nuclear speckles. They number 30-50 speckles per nucleus and are present in cells throughout the body, including in normal non-cancer cells. In cancer, nuclear speckles can take on an alternative state. We do not yet know if normal cells can sample this alternative state, but we do know that in certain cancers, particularly kidney cancer, the alternative speckle state corresponds to poorer survival and altered responsiveness to certain systemic anti-cancer treatments.

What is your current research focus?

In clear cell renal cell carcinoma (ccRCC), we lack effective ways to decide who should be subject to systemic treatment, and if so, which drug would be the most likely to work. We propose that the information we need to address these challenges is already present in the tumors in the form of nuclear speckles. Our working model is that nuclear speckles, by reflecting cancer-driving pathways, are a readout for the current and future biology of a tumor. We aim to evaluate the extent to which nuclear speckles can be used to improve patient outcomes and quality-of-life, hypothesizing that the state of nuclear speckles at the time of diagnosis can direct more personalized clinical care. The current proposal will evaluate a 600 patient clinically high-risk cohort treated with or without anti-angiogenesis therapy, and a 100-patient cohort treated with or without immune-checkpoint blockade, pembrolizumab. Evaluating nuclear speckles in these patient groups will test the utility of nuclear speckles as prognostic and predictive biomarkers. In parallel, comparing speckle states to the tumor microenvironment and other tumor features will provide potential insight into why speckles impact patient survival and response to therapy.

What kinds of new diagnostics or therapeutics could your research contribute to?

Ultimately, we aim to use nuclear speckles to help personalize patient care. The use of nuclear speckles as a prognostic indicator will help identify low-risk individuals who could be spared systemic therapy. Meanwhile, linking speckle state to differential response to therapy will provide a new way to select which individuals are likely to respond to a particular treatment. This will help maximize the anti-cancer benefit of therapy while reducing harmful side-effects of unneeded treatments.

What about your research could be most exciting for patients and families?

Over the recent decades, much progress has been made in identifying drivers of clear cell renal cell carcinoma (ccRCC) and developing systemic anti-cancer drugs to block those drivers. A current challenge is that these therapies only work for some individuals. What is exciting about our research is that it may not only provide a way to decide who is most likely to benefit from more aggressive treatment but may also indicate which treatment is more likely to be effective. This is helpful because it could help patients avoid unnecessary treatments that are less likely to work for their tumor and direct them toward therapies that are more likely to work.

What motivates you?

I am at my core a fundamental researcher. Meaning that I will pursue knowledge for the sake of knowledge with the belief that this approach will lead to new innovations that improve the human experience. I am motivated by a deep curiosity about what we do not yet know and the thrill of devising ways to illuminate these unseen spaces.

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

Beyond improving treatment options for kidney cancer patients, our research will provide insights into how nuclear speckles relate to other tumor features. We hope that this knowledge will further help personalize care by helping us form hypotheses about which other systemic therapies may work better depending on the state of the tumor’s nuclear speckles.