Frances Hundley

Frances Hundley is a molecular biologist focused on how cells decide which proteins to reuse and which to degrade and how this decision is disrupted in disease. Cells constantly make protein fate decisions—whether to reuse or degrade a protein—when a protein is damaged, no longer functional, or otherwise no longer needed. For example, proteins may need to be degraded in response to changing environmental conditions, to help communicate with other cells, and to allow a cell to grow and divide. Cells use two major mechanisms to adjust protein levels through regulated protein degradation: the ubiquitin proteasome system and the endolysosomal system. Frances previously investigated how the ubiquitin proteasome system helps cells respond to numerous conditions through CRISPR-Cas9 screening approaches. Prior to joining Smith College, Frances developed methods to measure protein recycling in the endolysosomal system in human neurons as a postdoctoral fellow in the laboratory of Wade Harper at Harvard Medical School. Using an interdisciplinary approach drawing on cell biology, molecular genetics, biochemistry, and computational biology, Frances’ current research aims to (1) determine which proteins are recycled in the endolysosomal system and how this occurs, (2) evaluate the consequences of neurodegenerative disease-associated mutations in the protein recycling and degradation pathways, and (3) investigate the mechanisms regulating protein recycling.

Teaching and mentoring students is one of Frances’ favorite parts of being a scientist, and she is committed to helping students feel that they can pursue and belong in a career in science or medicine.

Fu, T., Lee, C., Hundley, F.V., Paulo, J.A., Harper, J.W. (2026). Structural mechanisms of DNAJC13 dimeric assembly and InsP6 binding in recycling endosome regulation. bioRxiv. Pre-print.

Hundley, F.V.*, Gonzalez-Lozano, M.A.*, Gottschalk, L.M., Cook, A.N.K.**, Zhang, J., Paulo, J.A., Harper, J.W. (2024). Endo-IP and Lyso-IP toolkit for endolysosomal profiling of human-induced neurons. PNAS 121. (*co-first authorship. **indicates student or research associate mentee co-authors.)

Longhurst, A.D., Wang, K., Suresh, H.G., Ketavarapu, M., Ward, H.N., Jones, I.R., Narayan, V., Hundley, F.V., Hassan, A.Z., Boone, C., Myers, C.L., Shen, Y., Ramani, V., Andrews, B.J., Toczyski, D.P. (2024). The PRC2.1 subcomplex opposes G1 progression through regulation of CCND1 and CCND2. eLife.

Park, H., Hundley, F.V.*, Yu, Q.*, Overmyer, K.A., Brademan, D.R., Serrano, L., Paulo, J.A., Paoli, J.C., Swarup, S., Coon, J.J., Gygi, S.P., Harper, J.W. (2022). Spatial snapshots of amyloid precursor protein intramembrane processing via early endosome proteomics. Nature Communications 13: 6112. (*co-second authorship.)

Hundley, F.V. and Toczyski, D.P. (2021). Chemical-genetic CRISPR-Cas9 screens in human cells using a pathway-specific library. STAR Protocols 2: 100685.

Hundley, F.V., Sanvisens Delgado, N., Marin**, H.C., Carr**, K.C., Ruilin Tian, Toczyski, D.P. (2021). A comprehensive phenotypic CRISPR-Cas9 screen of the ubiquitin pathway uncovers roles of ubiquitin ligases in mitosis. Mol Cell 81: 1319-1336. (**indicates student or research associate mentee co-authors.)

Meza-Gutierrez, F., Hundley, F.V., Toczyski, D.P. (2015). Parallel Parkin: Cdc20 Takes a New Partner. Mol Cell 60: 3-4.