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Dive into Andrew’s OMICs study defining changes in the metabolome and transcriptome in a model of HFpEF, in the August Issue of JACC: Basic to Translational Science.
The issue included a commentary by the McKinsey lab, “Cat-apulting Toward a Molecular Understanding of HFpEF”.
Pooja and Joanne teamed up to write an extensive review of mitochondrial and metabolic dysfunction in neurodegenerative disease development and progression, “Reappraisal of metabolic dysfunction in neurodegeneration: Focus on mitochondrial function and calcium signaling” published in the July issue of Acta Neuropathologica Communications (https://doi.org/10.1186/s40478-021-01224-4).
Joanne and John published a commentary on the controversies of mitochondrial calcium content in heart disease entitled, “Is the failing heart starved of mitochondrial calcium?” published in the April 16th issue of Circulation Research (PMID: 33856917).
Michael received a Ruth L. Kirschstein National Research Service Award (F30 MD/PhD Fellowship) for his project “The Role of Acetyl-CoA Metabolism in Epigenetic Regulation of Myofibroblast Differentiation”. Congrats Mike!
Pooja Jadiya was awarded an NIH Pathway to Independence Award (K99/R00) from the National Institute on Aging (NIA) to enable her transition to independent faculty. The project is focused on “The role of mitochondrial calcium uptake in Alzheimer's disease”.
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Andrew and Michael’s review article titled “Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation” was published in the July 17th issue of Circulation Research (PMID: 32673537).
Joanne’s review article with lab alumnus Tim Luongo, titled “The debate continues - What is the role of MCU and mitochondrial calcium uptake in the heart?” (PMID:32353353) was published in the June 2020 issue of Journal of Molecular and Cellular Cardiology as part of a Special Issue, Unsolved mysteries and controversies of mitochondria in the heart.
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Dhanendra Tomar was awarded an NIH Pathway to Independence Award (K99/R00) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to enable his transition to independent faculty. Congrats DT!
Joanne was awarded an NIH F32 Ruth L. Kirschstein NRSA Postdoctoral Fellowship for her project on “Molecular Modulation of the Mitochondrial Na+/Ca2+ Exchanger as a novel therapeutic target for heart failure”. Congrats Joanne!
Jonathan and Emma’s review article titled “ MCUB and mitochondrial calcium uptake - modeling, function, and therapeutic potential” was published in Expert Opinions on Therapeutic Potential. (PMID: 32093523)
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Alyssa’s thesis work was published in the October issue of Nature Communication.
"Our experiments show that the accumulation of fibrotic cells results directly from mitochondrial calcium-dependent genetic reprogramming involving α-ketoglutarate, which changes the structure of chromatin, or DNA packaging - a phenomenon referred to as epigenetics, that is important in regulating gene expression," Dr. Elrod said. This the first time that extracellular signals directly modifying mitochondrial function have been linked to alterations in the cell nucleus for the formation of myofibroblasts.
"The key finding that a change in mitochondrial calcium uptake plays a central role in metabolic and genetic reprogramming presents new opportunities for investigation," explained Dr. Elrod. "We hope that the new pathways we've identified as essential to myofibroblast formation can be manipulated to treat fibrotic disease."
Jonathan published his thesis work defining a how MCUB alters the stoichiometry of the uniporter to modulate mitochondrial calcium uptake during stress.
The new research, published in the journal Circulation, identifies MCUB as a promising new target for the treatment of conditions that feature calcium overload and cell death – conditions that include heart failure, heart attack, stroke, and neurodegeneration.
“MCUB fine-tunes calcium uptake by mitochondria in injured heart tissue, in an attempt to limit calcium overload, which is a major contributor to cell death, particularly following a heart attack,” explained John W. Elrod, PhD, Associate Professor in the Center for Translational Medicine at the Temple University Lewis Katz School of Medicine and senior investigator on the new study.
Lambert JP, Luongo TS, Tomar D, Jadiya P, Gao E, Zhang X, Lucchese AM, Kolmetzky DW, Shah NS, Elrod JW. MCUB regulates the molecular composition of the mitochondrial calcium uniporter channel to limit mitochondrial calcium overload during stress. Circulation. 2019 Sep 19. 10.1161/CIRCULATIONAHA.118.037968
In the labs first foray into neurodegeneration, we report that alterations in mitochondrial calcium exchange proceed histopathology and cognitive decline in multiple Alzheimer’s disease (AD) models. The Pooja Jadiya led study also showed that these same mitochondrial alterations occur in the brains of patients diagnosed with sporadic AD. Her work has garnered numerous awards and been featured by numerous news outlets.
Jadiya P, Kolmetzky DW, Tomar D, Meco AD, Lombardi AA, Lambert JP, Luongo TS, Ludtmann MH, Praticò D, Elrod JW. Impaired mitochondrial calcium efflux contributes to Alzheimer’s disease progression. Nat Commun. 2019 Aug 29
DT, a senior postdoc in the lab, was awarded an American Heart Association Career Development Award for his proposal to define how mitochondrial structure is regulated in the context of ischemia-reperfusion injury. With this award DT will be transitioning to faculty position in the near future.
Andrew Gibb was awarded a postdoctoral fellowship (F32) from the NIH to study “Metabolic Control of Cellular Differentiation and the Fibrotic Response.”
Andrew and John published a commentary entitled, “Not just correlative: a new pathway defines how an ALDH2 SNP contributes to atherosclerosis” published in the January issue of The Journal of Clinical Investigation (PMID: 30507608).
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