My research is fundamentally dedicated to developing transformative immunotherapies for solid tumors, with a particular emphasis on rare, aggressive, and currently incurable malignancies. Since joining University Hospitals Seidman Cancer Center in 2026, I have established and now lead the inaugural Neuroendocrine Tumor (NET) research laboratory. In this role, my primary focus has been extra-pulmonary poorly differentiated neuroendocrine carcinomas, or EP-NECs. These are lethal tumors with no effective second-line therapy and a profoundly immunosuppressive tumor microenvironment that distinguishes them even from small cell lung cancer, with which they are often mistakenly grouped.
To tackle this challenge, I have engineered and validated next-generation SEZ6-targeted CAR T cells specifically for EP-NEC. My preliminary data demonstrate that SEZ6 is a viable surface target on patient-derived EP-NEC cells. However, conventional SEZ6-CART shows only modest efficacy, achieving just 34.9% tumor growth inhibition without complete responses. To overcome this limitation, I designed two armored CAR constructs: SEZ6-CART-αPD-L1, which reverses T cell exhaustion by blocking the PD-L1 checkpoint, and SEZ6-CART-41BB, which enhances CAR T cell persistence. I have also established a first-in-kind EP-NEC xenograft model using the NT38 cell line in humanized NSG mice, which allows me to test these therapies in a more clinically relevant setting. These studies are now supporting an NIH R21 application focused on relapsed and refractory EP-NEC.
Recognizing that animal models do not fully recapitulate the human tumor microenvironment, I have additionally proposed, through a submitted Harrington ScholarInnovator Award, an ex vivo patient-derived tumor slice culture platform. This platform preserves the intact human EP-NEC tumor microenvironment, complete with its native stromal and immune components. If funded, it will enable me to perform side-by-side testing of immune checkpoint inhibitors, bispecific T cell engagers, and antibody-drug conjugates, benchmarked directly against standard-of-care chemotherapy, all while retaining the architecture of human patient tissue.
Prior to my current position, my cancer research at City of Hope focused on leveraging tumor-tropic neural stem cells and exosome-based therapies to enhance delivery of oncolytic viruses and other therapeutic agents to metastatic tumors. I developed three novel chimeric poxvirus constructs targeting small-cell lung cancer, neuroblastoma, and neuroendocrine neoplasms. I also contributed to advancing CAR-NK cell therapies, which reduce the risk of neurotoxicity and cytokine release syndrome compared to CAR-T cells, and an mRNA cancer vaccine targeting specific biomarkers. My work on ovarian cancer, glioblastoma, and appendix neuroendocrine neoplasms has further broadened my expertise across multiple solid tumor types.
Looking forward, my ultimate goal is to integrate oncolytic virus-derived exosomes, armored CAR-NK cells, and mRNA vaccines into a cohesive platform for treating solid tumors. At present, I am fully focused on translating these approaches specifically for EP-NEC patients, with the aim of delivering IND-enabling data that will support first-in-human clinical trials for this devastating disease. Collaborating closely with my clinical collaborators and research team at University Hospitals, I am committed to bridging laboratory discoveries directly to bedside applications, ensuring that our novel immunotherapies reach the patients who currently have no viable treatment options.