Research
Dr. Curtis' research in her Immunometabolism and Cancer Immunology Lab focuses on immunometabolism, cancer immunotherapy and tumor antigens in ovarian cancer.
Immunometabolism
Immunotherapy has transformed the treatment landscape for many cancers. But patients with ovarian cancer derive limited benefit from current approaches. A major barrier is the unique metabolic and immunosuppressive tumor microenvironment at metastatic sites that can profoundly impair immune cell function.
Dr. Curtis' lab focuses on overcoming these barriers by engineering and metabolically reprogramming immune cells for ovarian cancer immunotherapy. Ongoing projects include:
- Developing chimeric antigen receptor (CAR)‑macrophage and CAR‑T cell therapies to function effectively within hostile metastatic niches.
- Examining how metabolites shape immune cell behavior in the tumor microenvironment.
By integrating cellular engineering with tumor immunometabolism, the Curtis lab aims to generate next‑generation immunotherapies capable of driving durable antitumor immunity in ovarian cancer.
Cancer immunotherapy
Immune checkpoint blockade has revolutionized cancer therapy. But these approaches have shown limited efficacy in high-grade serous ovarian cancer. This lack of response is often attributed to low tumor immunogenicity and ineffective antitumor immune activation.
The Curtis lab is investigating how tumor-intrinsic DNA damage response pathways contribute to immune evasion. The lab is particularly focusing on protein phosphatase 4 (PP4), which is a critical regulator of genome stability and cellular stress signaling. These processes influence antigen presentation and sensitivity to immune attack.
Our work tests the hypothesis that PP4 activity limits antitumor immunity in ovarian cancer and that targeting PP4 can enhance tumor immunogenicity. We are specifically exploring PP4 inhibition as a strategy to sensitize tumors to immune checkpoint blockade, enabling more effective combination immunotherapies.
By integrating tumor cell-intrinsic signaling with immune-based treatment strategies, this research aims to identify new combination approaches capable of improving responses to immunotherapy in ovarian cancer.
Tumor antigens
The lab's goal is to develop next-generation immunotherapy strategies that improve outcomes for patients with advanced-stage ovarian cancer. This effort integrates immunopeptidomics, antigen discovery and clinical translation, with a particular emphasis on identifying cryptic tumor antigens that are not predicted by conventional genomic approaches.
By defining each patient's tumor-specific immunopeptidome, the team identifies immunogenic tumor antigens, including cryptic peptides, that bind major histocompatibility complex molecules and elicit tumor-reactive T cell responses. These insights inform the design of personalized, multiantigen vaccines tailored to the unique antigenic landscape of an individual patient's cancer.
In parallel, we are conducting a phase 1 clinical trial evaluating autologous T cells activated with long peptides derived from the shared tumor antigen, MUC1, in patients with recurrent ovarian cancer (NCT06483048).
Together, this integrated research and clinical program aims to advance antigen-driven immunotherapies that enhance tumor immunogenicity to support durable clinical responses in ovarian cancer.