Our main goal is to understand how the synthesis and degradation of mRNAs and proteins are coordinated when cells respond to the accumulation of misfolded proteins.
To do so, we employ both experimental and computational approaches, we investigate whole genomes and individual genes, we probe proteins as well as RNAs.
We have developed the first tools to systematically explore the dynamic relationships between sequencing, ribosome footprinting, and proteomics data, and experimental methods to parse small protein samples from as few as 1,000 cells.We have quantified and compared transcription, translation, and protein stability of cells responding to protein misfolding stress. We discovered new links between small molecule metabolism and the stress response, roles of alternative splicing, and translation regulatory elements. We discovered new roles for the proteasome in induced motor neurons that might help combat Amyotrophic Lateral Sclerosis, and translation regulatory elements that affect the cellular stress response.
In more detail…
We continue our efforts in method development, both computationally and experimentally. We have developed the first tools to systematically explore the dynamic relationships between sequencing, ribosome footprinting, and proteomics data, and experimental methods to parse small protein samples from as few as 1,000 cells.
We quantify and compare transcription, translation, and protein stability of cells responding to protein misfolding stress. We discovered new links between small molecule metabolism and the stress response, roles of alternative splicing, and new translation regulatory elements.
We apply these quantitative methods to disease relevant systems: using the stem-cell derived system developed in Esteban Mazzoni’s lab, we explore expression differences between induced cranial and spinal motor neurons in response to protein misfolding stress to understand the molecular underpinnings of Amyotrophic Lateral Sclerosis, a major neurodegenerative disease.
We collaborate with various groups at NYU: with Andreas Hochwagen to map protein modification during meiosis, with Lionel Christiaen to understand post-transcriptional regulation of heart development, with Richard Bonneau on integration of transcriptional and post-transcriptional processes, and with Elodie Ghedin to map the host response to virus infections and vaccines and identify new biomarkers of infection, e.g. in Zika.
We have a long-standing collaboration with Hyungwon Choi (NU Singapore) to move towards what we think is the future: integrative systems proteomics approaches to better understand human disease, such as cancer.
A great summary of our research can be found in this talk as part of the Proteostasis Consortium Seminar Series.