Nilay Shah, MD
College of Medicine
Molecular Biology and Cancer Genetics
Cancer, Neuroblastoma, Breast Cancer, Sarcoma, Ewing, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm Metastasis, DNA Damage
The primary interest of Dr. Shah’s lab is the set of aberrations that lead to embryonic cancers, i.e. cancers of developmental errors. They are examining these errors in neuroblastoma, the most common extracranial solid tumor in children. This disease can manifest with very divergent presentations. In younger children (<18 months), the disease can present as large tumors or even with metastases to the liver, skin, and marrow. Most of these patients, however, have “low-risk” disease, even with these metastases, and are often managed with surgery or observation alone. Still, 20% will require some adjuvant chemotherapy for durable cure. In contrast, older patients often present with high-grade disease and with metastases including to the bone; despite toxic multimodal therapies including high-dose chemotherapy, radiation therapy, immunotherapy and differentiation agents <50% of these patients survive their disease. Identification of novel biomarkers of disease severity are needed to better delineate these patient groups (e.g., those “low-risk” patients who will need chemotherapy for cure, and those high-risk patients who will not respond to current treatments). This will also lead to novel therapeutic targets, which will improve outcomes and reduce toxicity. Dr. Shah’s lab is currently examining components of the HOX gene pathway, the master regulatory system for normal tissue differentiation and development, to better understand the aberrations that lead to neuroblastomagenesis. This has lead to the identification of multiple targets for further validation, among the HOX genes themselves, as well as in associated long noncoding RNAS (lncRNAs) and the HOX cofactors in the TALE family of genes (PBX, MEIS, and PKNOX paralogs). Evaluation of some of these genes includes validation of select genes for utility as a clinical biomarker, to guide treatment approach. The lab currently uses primary tumors and established neuroblastoma cell lines as the main models of disease, using a variety of molecular and cellular approaches including gene expression analysis by RT-qPCR and high-throughput techniques, protein analysis by Western blot, IHC, and IF, and protein interactions with other proteins, DNA, and or RNA. They are also expanding the models in 2014 into zebrafish models of neuroblastoma, in collaboration with the Zebrafish Core facility at OSU, and into use of circulating tumor cells from patients to generate banks of pre- and post-treatment cells and primary cell cultures.