A multidisciplinary project combines genomics, stem-cell differentiation, super-resolution microscopy, and AI/ML to reveal how closely related transcription factors steer development and neuron patterning along the spinal axis.

Researchers will investigate common Hox gene mutations linked to syndactyly and hand-foot-genital syndrome to understand how alterations in transcription factor biochemistry affect activity and development.

The team will map transcription factor binding sites with ChIP-seq, use high-resolution imaging to pinpoint protein-DNA interactions, and study how factors access open versus closed chromatin and why binding preferences differ.

Long-term aims include creating instruction manuals to guide stem cells toward specific lineages, enabling regenerative medicine applications and extending methods to other transcription factor families.

Artificial intelligence models, trained on binding and protein data, will predict transcription factor binding across cell types with a emphasis on interpretability over black-box predictions.

A collaborative NIH grant of about $3.8 million supports Penn State and NYU in exploring how transcription factors regulate gene expression during development and why similar factors yield different neuronal outcomes.

The research will focus on homeodomain transcription factors from Hox genes to understand how they pattern the mammalian spinal cord and motor neurons, including why related factors produce distinct neuron types.