Teruel Lab Research

Our overall goal is to understand the interconnected regulation of cell movement, proliferation and differentiation in health and disease. We investigate such cellular control systems by identifying key signaling components and measure when and where signaling occurs in normal, cancer and other disease states. We use live-cell microscopy to watch cells signal as they move, enter the cell cycle or differentiate. To understand these cell signaling processes requires that we develop and apply new reporter and perturbation tools in combination with advanced automated live-cell fluorescent microscopes we have setup in the lab. These live-cell approaches are closely integrated with automated multiplexed immunostaining, and machine learning, which allows us to comprehensively explore how mammalian regulatory systems are build. We further integrate these approaches with systematic genomic and targeted screens, single-cell RNAseq analysis, and quantitative models of signaling pathways. Specific projects typically focus on in vitro models or organoids, with the ultimate goal to understand processes such as adipogenesis (differentiation of fat cells) or neurogenesis which often requires that we validate key findings using mouse models.

We do not yet understand how hormonal oscillations, the circadian clock and the cell cycle coordinate cell differentiation processes for tissue development and maintenance. We are developing in vitro 2D and 3D models that can be used together with automated microscopy to track thousands of individual cells as their signals oscillate and they chose trajectories towards one or more differentiated states. Current model systems in the lab include adipogenesis and neurogenesis and focus for example on the questions how cells integrate different signals to balance the number of differentiated cells while maintaining pools of progenitor cells, and how cells select which of two differentiation trajectories to take.

See the following publications for more about this work:

  • Zhao ML, Rabiee AR, Kovary KM, Bahrami-Nejad Z, Taylor B, Teruel MN. (2020). Molecular competition in G1 controls when cells simultaneously commit to terminally differentiate and exit the cell-cycle. Cell Reports Jun 16;31(11):107769. doi: 10.1016/j.celrep.2020.107769. PMID: 32553172.
  • Bahrami-Nejad Z*, Zhao ML*, Hunderdosse D, Tholen S, Tkach KE, van Schie S, Chung M, Teruel MN. (2018). A transcriptional circuit filters oscillating circadian hormonal inputs to regulate fat cell differentiation. Cell Metabolism Apr 3, 27(4):854-868.e8. doi: 10.1016/j.cmet.2018.03.012. PubMed PMID: 29617644. *equal contribution.

 

Adipocytes
A main research focus in the lab is on adipogenesis (fat cell differentiation) since defects in this process leads to obesity, diabetes, cardiovascular disease, and many types of cancer. A main issue in obesity and metabolic disease is faulty cell differentiation and dedifferentiation with adipocytes changing their differentiation program to become unresponsive to insulin. We are focusing on the idea that preventing the dedifferentiation of mature adipocytes and generating new healthy adipocytes improves metabolic health. Thus, the question we are asking is how one can control the number of newly differentiated cells and how one can maintain differentiated cells in a healthy state and prevent their dedifferentiation. We are using both in vitro models and in vivo validation in mice to understand how one can increase the number of differentiated cells and also lock differentiated adipocytes in a healthy state.

See the following publications for more about this work:

  • Ota A, Kovary KM, Wu OH, Ahrends R, Costa MJ, Shen W, Feldman BJ, Kraemer FB, Teruel MN. (2015). Using SRM mass spectrometry to profile nuclear protein abundance differences between adipose tissue depots of insulin resistant mice. Journal of Lipid Research May; 56(5):1068-78. Epub Apr 3. PMID: 25840986.
  • Ahrends R, Ota A, Kovary KM, Kudo T, Park BO, Teruel MN. (2014). Controlling low rates of cell differentiation through noise and ultra-high feedback. Science Jun 20; 344:1384-9. PMID: 24948735. Awarded an Editors’ Choice rating by signaling editors of Science.
  • Park BO, Ahrends R, Teruel MN. (2012). Consecutive positive feedback loops create a bistable switch that controls preadipocyte to adipocyte conversion. Cell Reports Oct 25; 2(4): 976-90. Epub 2012 Oct. 11. PMID: 23063366