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Sonya Neal


"Understanding the mechanistic underpinnings and medical importance of misfolded proteins"

Life is harsh, and hard on protein structure. Continuously-produced misfolded proteins represent a threat to proper cell and organ function. To survive this threat, organisms are equipped with quality control systems to maintain properly folded proteins; a process known as protein homeostasis. For the past two decades, it has become increasingly clear that protein homeostasis is critical to the health of cells and organisms. Defects in protein homeostasis underlie many of the most pressing maladies, including aging, cancer and neurodegenerative diseases. Our research strives to understand the basic biology of protein homeostasis and how organisms use quality control pathways to mitigate this universal biological stress. There are three questions that motivate our research:

  1. How do cells maintain protein homeostasis?
  2. How do changes in protein homeostasis lead to pathology?
  3. Can modulation of protein homeostasis be used to treat disease?

Our research aim is to understand the cellular and tissue-specific roles of factors involved in protein quality control pathways, with a particular emphasis on the pathways that detect and specifically destroy these dangerous molecules. An understanding of these pathways allows us to define the mechanisms that protect the organismal proteome in health and disease, and eventually devise methods to harness cellular quality control to modify the proteome in the laboratory and the clinic. As a first step towards this goal, we are focused on discovering and studying proteostasis pathways in yeast, mammalian cells and zebrafish, allowing us to synergistically capitalize on the investigative strengths that each has to offer. We take advantage of the laboratory’s unique set of skills in genetics, biochemistry, functional genomics, cell and molecular biology to extend these lines of inquiry and to train the next generation of scientific leaders.

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  • A. Nejatfard, Nicholas Wauer, S. Bhaduri, A. Conn, S. Goukanti, N. Singh, T. Kuo, R. Kandel, R. Amaro, and S.E.Neal. (2021). Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion function for retrotranslocation of ER multi-spanning membrane substrates. Cell Reports doi:
  • S. Bhaduri and S.E.Neal. (2021). Assays for studying normal versus suppressive ERAD-associated retrotranslocation pathways in yeast. STAR Protocols.
  • M.,Flagg, M., Wangeline, S,. Holland, S.E., Neal and R.Y., Hampton. (2021) Inner-Nuclear-Membrane-Associated Degradation Employs Dfm1-Independent Retrotranslocation and Alleviates Misfolded Transmembrane-Protein Toxicity.” MBoC.
  • P.E., Sam, E., Calzada, M., Acoba, T., Zhao, Y., Watanabe, A., Nejatfard, J.C., Trinidad, T., Shutt, S.E.Neal, and S.M., Claypool. (2021). Impaired phosphatidylethanolamine metabolism activates a reversible stress rersponse that detects and resolves mutant mitochondrial precursors. iScience.
  • R. Kandel and S.E.Neal. (2020). The role of rhomboid superfamily members in protein homeostasis: Mechanistic insight and physiological implications. BBA Molecular Cell Research.
  • S.E. Neal, D. Syau, A. Nejatfard, S. Nadeau, and R.Y Hampton. 2020. HRD complex self-remodeling enables novel route of ERAD-M retrotranslocation. iScience.
  • Neal, S.E., Duttke, S, R. Hampton. (2019). Assays for protein retrotranslocation in ERAD. Methods of Enzymology. 618.
  • Neal, S.E., Jaeger, P., Duttke, S., Benner, C., Glass, C., Ideker, T., R. Hampton. (2018). The Dfm1 Derlin is Required for ERAD Retrotranslocation of Integral Membrane Proteins. Molecular Cell. 69, 306-320. (Highlighted: Avci, D. and Lemberg, A. (2018) Molecular Cell)
  • Neal, S.E., Dabir, D.V., Boon, C., and Koehler C.M. (2017). Osm1 is an electron acceptor of Erv1 in the Mia40-dependent import pathway. MBoC. 28, 2773-2785.
  • Neal, S.E., Mak, R., Bennett, E.J., and Hampton, R. (2017). A Cdc48 “Retrochaperone” Function Is Required for the Solubility of Retrotranslocated, Integral Membrane Endoplasmic Reticulum-associated Degradation (ERAD-M) Substrates. J. Biol. Chem. 292, 3112–3128.
  • Vashistha, N., Neal, S.E., Singh, A., Carroll, S.M., and Hampton, R.Y. (2016). Direct and essential function for Hrd3 in ER-associated degradation. Proc. Natl. Acad. Sci. 113, 5934–5939.
  • Neal, S.E., Dabir, D. V., Tienson, H.L., Horn, D.M., Glaeser, K., Ogozalek Loo, R.R., Barrientos, A., and Koehler, C.M. (2015). Mia40 Protein Serves as an Electron Sink in the Mia40-Erv1 Import Pathway. J. Biol. Chem. 290, 20804–20814.
  • Tienson, H.L., Dabir, D. V, Neal, S.E., Loo, R., Hasson, S.A., Boontheung, P., Kim, S.-K., Loo, J.A., and Koehler, C.M. (2009). Reconstitution of the mia40-erv1 oxidative folding pathway for the small tim proteins. Mol. Biol. Cell 20, 3481–3490.


Dr. Neal received her Ph.D. from U.C. Los Angeles in 2013 after working in the laboratory of Dr. Carla Koehler. She then carried out her postdoctoral studies at U.C. San Diego in the laboratory of Dr. Randolph Hampton. She was the recipient of the Burroughs Wellcome Postdoctoral Diversity Enrichment Award and Ruth L. Kirschstein NRSA Postdoctoral Fellowship. Dr. Neal joined the faculty in 2018.

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