Research
Our work focuses on these key areas
Controlling Mitochondrial Calcium Uptake
The mitochondrial calcium uniporter (mtCU) is the main route for calcium entry into mitochondria, a process that links energy output (ATP) to demand. Excess levels of mitochondrial calcium can trigger cell death pathways and is a hallmark of cardiac disease, so recent research has focused on the effects of blocking mitochondrial calcium uptake.
One of the lab's primary interests is identifying changes in cell signaling that result from blocking mitochondrial calcium uptake. We hope to define compensatory pathways that are activated in a time-dependent manner upon mtCU inhibition, and characterize their roles in modulating metabolism and cell death programs.
Mitochondrial Stress Signaling Pathways
Mitochondrial calcium overload is a form of mitochondrial stress that is associated with multiple age-related degenerative diseases. We are interested in mitochondrial-to-nuclear retrograde signaling pathways that are activated by this form of mitochondrial stress.
We are using RNASeq approaches to investigate whether mitochondrial calcium overload initiates a global transcriptional response. Expanding our analysis to other forms of mitochondrial stress will reveal whether there are overlapping mitochondrial-to-nuclear retrograde signaling pathways or whether different stress sources turn on distinct pathways with divergent downstream cell fate responses.
Mitochondrial Calcium and Muscle Repair
Calcium regulation plays an important role in muscular dystrophies, and mitochondrial calcium overload is also associated with muscle weakness. We are interested in how modulating mitochondrial calcium could affect muscle repair and regeneration after injury, potentially via disrupting the differentiation of muscle satellite cells. Ultimately, we hope to decipher how mitochondrial health or stress can play roles in regulating cell fate decisions in terms of not only energy utilization or cell death but also stem cell differentiation and tissue repair.
Publications
2020
Puente BN, Sun J, Parks RJ, Fergusson MM, Liu C, Springer DA, Aponte AM, Liu JC*, Murphy E*. MICU3 plays an important role in cardiovascular function. Circ Research, in press. *co-corresponding
Liu JC (2020). Is MCU dispensable for normal heart function? J Mol Cell Cardiol. 143: 175–183.
Liu JC, Syder NC, Ghorashi NS, Willingham TB, Parks RJ, Fergusson MM, Liu J, Holmström KM, Menazza S, Springer DA, Liu C, Glancy B, Finkel T, Murphy E. (2020). EMRE is essential for mitochondrial calcium uniporter activity in a mouse model. JCI Insight. 5(4):e134063.
2018
Parks RJ, Murphy E, Liu JC. (2018). Mitochondrial Permeability Transition Pore and Calcium Handling. Methods Mol Biol. 1782:187-196.
2017
Liu JC, Parks RJ, Liu J, Stares J, Rovira II, Murphy E, Finkel T. (2017). The In Vivo Biology of the Mitochondrial Calcium Uniporter. Adv Exp Med Biol. 982:49-63.
Porter JR, Fisher BE, Baranello L, Liu JC, Kambach DM, Nie Z, Koh WS, Luo J, Stommel JM, Levens D, Batchelor E. (2017). Global Inhibition with Specific Activation: How p53 and MYC Redistribute the Transcriptome in the DNA Double-Strand Break Response. Mol Cell. 67(6):1013-1025.
2016
Liu JC, Liu J, Holmström KM, Menazza S, Parks RJ, Fergusson MM, Yu ZX, Springer DA, Halsey C, Liu C, Murphy E, Finkel T. (2016). MICU1 Serves as a Molecular Gatekeeper to Prevent In Vivo Mitochondrial Calcium Overload. Cell Reports. 16(6):1561-1573.
Paek AL, Liu JC, Loewer A, Forrester W, and Lahav G. (2016). Cell-to-cell variation in p53 dynamics leads to fractional killing. Cell. 165(3):631-642.
2015
Holmström KM, Pan X, Liu JC, Menazza S, Liu J, Nguyen TT, Pan H, Parks RJ, Springer DA, Anderson SA, Murphy E, Finkel T. (2015). Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter. J Mol Cell Cardiol. 85:178-82.
Finkel T, Menazza S, Holmström KM, Parks RJ, Liu J, Sun J, Liu J, Pan X, Murphy E. (2015). The ins and outs of mitochondrial calcium. Circ Res. 116(11):1810-9.
2014
Liu JC, Lerou PH, and Lahav G. (2014). Stem cells: balancing resistance and sensitivity to DNA damage. Trends Cell Biol. 24(5):268-74.
2013
Liu JC, Guan X, Ryan JA, Rivera AG, Mock C, Agrawal V, Letai A, Lerou PH, and Lahav G. (2013). High mitochondrial priming sensitizes hESCs to DNA-damage-induced apoptosis. Cell Stem Cell. 13(4):483-91.