Cellular Energetics (current)


Despite detailed knowledge of metabolic pathways, it remains unclear what the spatiotemporal dynamics of energy usage in cells are, how cells partition energy among different cellular processes and the associated energetic constraints. A major challenge is to measure metabolic fluxes in living cells with sufficient spatiotemporal resolution. To overcome this challenge, I developed a biophysical model to infer mitochondrial metabolic fluxes from fluorescence lifetime imaging of NADH. The model is validated by direct measurements of oxygen consumption rate in mouse oocytes and human tissue culture cells, providing a general method to measure metabolic fluxes in living cells with subcellular resolution. Using this method, I discovered homeostasis and heterogeneity of mitochondrial metabolic fluxes in mouse oocytes. 

The goal is to use this method to study spatiotemporal regulation of metabolic fluxes, energetic costs of cellular processes and the interplay between energy dissipation and self-organization in cells. I am currently studying how mitochondrial metabolism correlates with spindle self-organization, chromosome segregation and early embryo development. This research could provide insights into the role of mitochondrial dysfunctions in infertility.

Publications


Metabolic state of human blastocysts measured by fluorescence lifetime imaging microscopy


M. Venturas, J. S. Shah, X. Yang, T. H. Sanchez, W. Conway, D. Sakkas, D. J. Needleman

Human Reproduction, 2022 Jan 6


Metabolic imaging of human cumulus cells reveals associations among metabolic profiles of cumulus cells, patient clinical factors, and oocyte maturity


Marta Venturas, Xingbo Yang, Kishlay Kumar, Dagan Wells, Catherine Racowsky, Daniel J. Needleman

Fertility and Sterility, 2021 Sep 2


Physical bioenergetics: Energy fluxes, budgets, and constraints in cells.


Xingbo Yang, Matthias Heinemann, Jonathon Howard, Greg Huber, Srividya Iyer-Biswas, Guillaume Le Treut, Michael Lynch, Kristi L Montooth, Daniel J Needleman, Simone Pigolotti, Jonathan Rodenfels, Pierre Ronceray, Sadasivan Shankar, Sadasivan Shankar, Sadasivan Shankar, Iman Tavassoly, Shashi Thutupalli, Denis V Titov, Jin Wang, Peter J Foster

Proceedings of the National Academy of Sciences of the United States of America, vol. 118(26), 2021 May 28


Combined noninvasive metabolic and spindle imaging as potential tools for embryo and oocyte assessment.


Tim Sanchez, Marta Venturas, S Ali Aghvami, Xingbo Yang, Seth Fraden, Denny Sakkas, Daniel J Needleman

Human Reproduction, vol. 34(12), 2019 Oct 30, pp. 2349-2361