1). Stress responses and residual tumor development
2). Transcriptional control of cellular states
3). Lysosome-dependent cell death in residual tumors
4). Stromal regulation of residual tumor survival
5). Therapy-induced senescence in tumor and normal tissues
We study the mechanisms and targeting of residual tumors following chemotherapy and/or targeted therapy, with the ultimate goal of preventing tumor recurrence.
Tumor recurrence remains a major clinical challenge, as chemotherapy often leaves behind a population of residual tumor cells capable of driving disease relapse. This phenomenon is observed across multiple malignancies, including breast, lung, colorectal cancers, and leukemia. In breast cancer, the extent of residual disease following neoadjuvant therapy strongly predicts patient outcomes, underscoring its clinical significance. However, effective strategies to eliminate these cells remain limited, largely due to an incomplete understanding of their biology.
Our research focuses on the adaptive mechanisms that enable residual tumor cells to survive therapeutic stress. Rather than relying on stable genetic mutations, these cells enter a reversible drug-tolerant persister state, driven by dynamic, non-genetic programs. This transient state allows them to withstand cytotoxic treatments and later re-enter proliferative growth, contributing to recurrence.
The central goal of our laboratory is to define the core biology of therapy-induced residual disease and to identify targetable vulnerabilities unique to this state. By integrating functional genomics, pharmacology, and mechanistic studies, we aim to develop strategies that selectively eradicate residual tumor cells and improve long-term treatment outcomes.
Biography
Dr. Li completed his medical school training at Beijing Medical University and earned his graduate degree from Penn State University. He subsequently pursued postdoctoral training at Stanford University, where he remained for several years as an instructor. He later moved to Houston Methodist to establish his independent research laboratory.
Distinctions:
American Cancer Society Research Scholar Award
Career Cornerstone Award, Houston Methodist
Innovation Award, Houston Methodist Neal Cancer Center
