Nathan M Merrill, PhD

My long-term goal is to build the foundation to function as an independent investigator focused on precision oncology. My research interests involve the identification of biomarkers of drug efficacy and resistance in highly aggressive forms of cancer, with the ultimate goal of pairing the right patient with the right therapy. My academic training and research experiences have provided me with a multidisciplinary background in chemistry, biochemistry, genetics, molecular biology, experimental therapeutics, and translational cancer biology. As an undergraduate at the University of Michigan, I conducted research with Dr. Mi Hee Lim to develop small-molecule metal chelators that target Aβ plaques in Alzheimer’s disease, work that contributed to a second-author publication characterizing metal chelators and their corresponding metal complexes. As a doctoral student with Dr. Jeff MacKeigan at the Van Andel Research Institute, my research focused on elucidating the role of PI3K-C2α in the autophagy pathway and identifying small-molecule inhibitors of its kinase domain. I identified PI3K-C2α as a node connecting the endocytic and autophagy pathways, suggesting that PI3K-C2α may be a critical component of the complex that directly incorporates endocytic membrane sources into the autophagy pathway, and authored a first-author publication on this work. As a postdoctoral researcher at the University of Michigan, I expanded my expertise in experimental therapeutics, functional drug testing, and molecular correlates of drug response. I integrated drug screening with molecular characterization in triple-negative breast cancer and bladder cancer models, authoring publications that established the foundation for much of my current research program. I also helped establish a precision medicine platform that uses patient-derived material from the operating room to generate short-term organoid models for functional drug testing.
As a research investigator and now as a Research Assistant Professor at the University of Michigan, I have built on these experiences to expand our precision medicine platform across multiple aggressive solid tumors, including breast cancer brain metastases, triple-negative breast cancer, bladder cancer, and EML4-ALK–driven lung cancer. My current work integrates patient-derived organoids, patient-derived xenografts, functional drug response assessment, and multiomic profiling to identify molecular determinants of therapeutic response and resistance. This platform has supported studies of breast cancer brain metastases, fatty acid synthase inhibition in TNBC brain metastasis models, molecular correlates of gemcitabine response in patient-derived bladder cancer organoids, and emerging efforts to predict response to therapies such as enfortumab vedotin and targeted therapies in lung cancer. Together, these studies position me to investigate how tumor heterogeneity, cell-state plasticity, and the tumor microenvironment influence therapeutic response. My current research program is designed to advance translational science by developing functional and molecular approaches that inform individualized treatment strategies for patients with aggressive cancers.

My long-term research interests involve the identification of biomarkers of drug efficacy in highly aggressive forms of cancer. Utilizing tumor characteristics, I hope to pair the right patients with the right drugs.