Our Research

Decoding the Molecular Logic of Neural Development

The development of sensory neural systems represents the culmination of a complex choreography of transcription complex functions and epithelial morphogenetic events. Frequently, it is these same or similar developmental processes that lie at the root of many human diseases, including cancer.

Our Long-Term Goal: To decode the molecular logic that confers both precision and robustness to neural system development, and to learn how these processes go awry in disease.

Our work focuses on studying the conserved Hippo-Yki(YAP1), mTOR-Mitf(MITF), and So(SIX1)-Eya(EYA1) signaling cascades in developing sensory epithelia, using the Drosophila eye disc as a model system. In humans, mutations in these regulators are linked to congenital blinding diseases and hearing loss. We are fascinated by how organisms have repurposed this small set of transcription regulators to control diverse and often disparate cellular and neurodevelopmental processes.

A fluorescent confocal micrograph showing neural development in a Drosophila (fruit fly) larval eye imaginal disc.

Fig. 1: Drosophila retinal neurons (magenta) and their axons (green) in a larval eye disc.

Areas of Investigation

Four-panel scientific diagram and light micrograph panel comparing normal and abnormal Drosophila eye development.

Fig. 2: Developmental juxtaposition of retinal and support cell domains of the ocular epithelium is critical for eye morphogenesis.

Retina (purple nuclei) and support cells (blue nuclei) are aligned in wildtype eye discs (A) leading to normal eye formation (A’). Tissue misalignment in development (B) results in malformed adult eyes (B’)

Determinants of Epithelial Topology During Organ Formation

The morphogenesis of complex epithelia into functional organs represents the culmination of myriad cell-intrinsic and tissue-scale events, often requiring interactions among discrete epithelial domains and the extracellular matrix.
Our overarching goal in this project is to elucidate the mechanisms that allow complex epithelia to maintain their scaling and juxtaposition during organogenesis. In Drosophila, Mitf and Yki serve to maintain eye imaginal disc and ultimately retina topology. Our work has shown that there is a putative causal link between Yki activity and the extracellular matrix.

Repurposing Transcription Regulators During Development

A remarkably small number of factors (~755 DNA-binding transcription regulators in the fruit fly Drosophila melanogaster) must be used combinatorially or iteratively throughout development to generate the cellular complexity typical of multicellular organisms.

While the iterative deployment of transcription regulators is an accepted phenomenon, how cells respond acutely to the need to repurpose them is not well understood. Molecular events in the developing fly eye offer our lab a unique opportunity to investigate this transition in transcription regulator function with high molecular, genetic, and temporal precision.

A scientific schematic diagram mapping two distinct signaling pathways that control separate cellular outcomes in the Drosophila eye epithelium, "fate" and "form".

Fig. 3: A switch in genetic and transcription regulator function occurs during Drosophila eye development.

Transcription regulators (Mitf, Yki, Hth) have discrete functions in eye epithelial cells (PE) during consecutive phases of Drosophila larval development. How this switch occurs, and what genes are regulated to control these distinct developmental outcomes are not understood.

Image illustrating a molecular pathway diagram focused on transcription complex assembly and gene regulation.

Fig. 4: Missense mutations may differentially affect how transcription complexes assemble and function.

Missense mutations in SIX and EYA are associated with branchio-otic syndromes (BOS) which present with varying comorbidities in different tissues and organs. Understanding how these mutations impact the molecular functions of these transcription regulators will help us develop new approaches to treating these diseases.

Molecular Genetic Analysis of Missense Mutations in Disease

Congenital hearing loss is frequently observed as a comorbidity in patients diagnosed with branchio-otic syndromes (BOS)—affecting roughly 1 in 40,000 live births. Nearly 50% of BOS cases are explained by monogenic inheritance of dominant alleles encoding co-factor EYA1 or transcription factor SIX1.

Most characterized BOS mutations affect a single amino acid in these proteins (missense mutations). Our goal is to identify the specific molecular complexes and gene expression programs that are dysregulated in BOS to help pave the way for new therapeutic approaches.

Why Drosophila melanogaster?

The fruit fly (Drosophila melanogaster) has played a critical role as a model organism for developmental biology research, beginning with pioneering work by Nobel Laureate Thomas Hunt Morgan, here, in New York State. As a model organism, it is easy to maintain, develops quickly, and has far less genetic redundancy than humans or other vertebrate models. Drosophila was among the first Metazoan organisms to have its genome fully sequenced, and the tools developed to annotate the Drosophila genome were critical to the success of the Human Genome Project.

Funding & Acknowledgments

The lab is currently funded by a grant from the National Eye Institute (NEI; R21) and through support from SUNY Upstate and the Department of Neuroscience and Physiology.

Join the Lab

Students interested in our work should apply to the Summer Undergraduate Research Fellowship (SURF) program, or to the Upstate PhD program, offered through the SUNY Upstate College of Graduate Studies.

SURF Program

Upstate PhD program

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