Prof. Dr. Alexander Tarakhovsky
Research Area: Epigenetic Mechanisms of Diapause and Dormancy
Branches: BiochemistryMetabolismMolecular Biology
Website: Tarakhovsky Lab
1. Research Background:
The ability of unicellular and multicellular organisms to enter the state of diapause characterized bysuspended growth and significantly reduced energy metabolism is essential for the organism's survival in response to nutrient deprivations and other adverse environmental conditions. The diapause-like conditions can also occur during cell-autonomous attenuation of the anabolic processes and active metabolism. The naturally occurring diapause-like dormant cells include memory immune cells, dormant tissue-specific stem cells, and dormant tumor cells.
We discovered a novel epigenetic mechanism of diapause induction. We identified a group of chromatin-bound proteins that can operate as sensors of nutrient supply and contribute to establishing the diapause-specific transcriptional state. We hypothesize that naturally occurring diapause in dormant tumor cells or memory immune cells involves the nutrient- independent epigenetic switch that drives and supports dormancy.
2. Research questions addresses by the group:
Our overreaching aim is to define the mechanism of the cell-autonomous modulation of diapause-inducing epigenetic regulators. We are also interested in understanding the mechanism of transcription homeostasis during long- lasting dormancy. We will focus on defining general principles of gene transcription and mRNA maintenance during dormancy.
3. Possible projects:
- The metabolic control of dormant cells' epigenetic state
- Epigenetic control of transcriptional homeostasis in dormant cells
- The transient dormancy in complex tissues and its role in longevity
4. Applied Methods and model organisms:
- In vitro cultured cell lines, mouse ES cells, ex vivo isolated mouse cells
- Chromatin studies, e.g. ChIP-sequencing, ATAC seq, sub-nuclear domains, RNA transcription, and stability. Large-scale gene analysis at the population and single-cell resolution.
5. Desirable skills and qualifications:
Molecular biology, biochemistry, and genetics, immunology
- Su I-H, Dobenecker M, Oser M, Basavaraj A, Margueron R, Viale A, Reinberg D, Wulfing C, Tarakhovsky A. Polycomb group protein Ezh2 controls actin polymerization and cell signaling. Cell. 2005; 121:425-36. PMID: 15882624
- Sampath SC, Marazzi I, Yap KL, Sampath SC, Krutchinsky AN, Mecklenbräuker I, Viale A,Rudensky E, Zhou MM, Chait BT, Tarakhovsky
A. Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol Cell. 2007; 27(4):596-608. PMID: 17707231
- Marazzi, I, Ho J, Kim J, Manicassamy B, Dewell S, Albrecht RA, Prinjha RK, Jeffrey KL, Lee K, Garcia-Sastre A, Roeder R, Tarakhovsky A. Suppression of the antiviral response by an influenza "histone mimic". Nature. 2012 Mar 14;483(7390):428-33. PMCID: PMC3598589
- Schaefer U, Ho JS, Prinjha RK, Tarakhovsky A. The "Histone Mimicry" by Pathogens. Cold Spring Harb Symp Quant Biol. 2014 Apr 28. [PMID: 24733380; PMCID PMC5406129
- Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK, Lee K, Tarakhovsky A., Suppression of inflammation by a synthetic histone mimic. Nature. 2010; Dec 23;468(7327):119-23. PMID: 21068722; PMCID PMCID PMC5415086
- Mourão D, Chen S, Schaefer U, Bozzacco L, Carneiro LA, Gerber A, Adura C, Dill BD, Molina H, Carroll T, Paul M, Bhanu NV, Garcia BA, Joberty G, Rioja I, Prinjha RK, Roeder RG, Rice CM, MacDonald MR, Patel D, Tarakhovsky A. A histone-like motif in yellow fever virus contributes to viral replication. bioRxiv. 2020 May 6. DOI: doi.org/10.1101/2020.05.05.078782