Dr. Carla Nasca's Epigenetics and System Neuroscience laboratory is working on an innovative model of epigenetic mechanisms of neuroplasticity to stress with a new angle on the communication between mitochondria and cell nuclei. Key to this framework is the pivotal mitochondrial metabolite L-acetyl-carnitine or LAC, which our group discovered as a novel epigenetic modulator of glutamatergic function and a promising therapeutic target for clinical endophenotypes of depression – a prodrome to Alzheimer’s Disease. Her laboratory also uses computational approaches together with emerging technologies to isolate patient-derived exosomes for identifying in vivo neural mechanisms of main CNS diseases (mood and cognitive disorders) and potential biomarkers of the responses to antidepressant candidates (LAC), drugs (ketamine) and brain stimulation (TMS).
Dr. Nasca's research has been recognized with awards from the Blavatnik Foundation for Innovative Research, the Hope for Depression Research Foundation, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation and the Falk Foundation for Transformative Research.
Nasca C, Dobbin J, Bigio B, Watson K, de Angelis P, Kautz M, Cochran A, Mathé AA, Kocsis JH, Lee FS, Murrough JW, McEwen BS, Rasgon N. Insulin receptor substrate in brain-enriched exosomes in subjects with major depression: on the path of creation of biosignatures of central insulin resistance. Mol Psychiatry. 2021 Sep;26(9):5140-5149. doi: 10.1038/s41380-020-0804-7. Epub 2020 Jun 15. PMID: 32536688; PMCID: PMC7787430.
Nasca C, Menard C, Hodes G, Bigio B, Pena C, Lorsch Z, Zelli D, Ferris A, Kana V, Purushothaman I, Dobbin J, Nassim M, DeAngelis P, Merad M, Rasgon N, Meaney M, Nestler EJ, McEwen BS, Russo SJ. Multidimensional Predictors of Susceptibility and Resilience to Social Defeat Stress. Biol Psychiatry. 2019 Sep 15;86(6):483-491. doi: 10.1016/j.biopsych.2019.06.030. Epub 2019 Jul 29. PMID: 31466563; PMCID: PMC6730655.
Nasca C, Bigio B, Lee FS, Young SP, Kautz MM, Albright A, Beasley J, Millington DS, Mathé AA, Kocsis JH, Murrough JW, McEwen BS, Rasgon N. Acetyl-l-carnitine deficiency in patients with major depressive disorder. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8627-8632. doi: 10.1073/pnas.1801609115. Epub 2018 Jul 30. PMID: 30061399; PMCID: PMC6112703.
Nasca C, Bigio B, Zelli D, de Angelis P, Lau T, Okamoto M, Soya H, Ni J, Brichta L, Greengard P, Neve RL, Lee FS, McEwen BS. Role of the Astroglial Glutamate Exchanger xCT in Ventral Hippocampus in Resilience to Stress. Neuron. 2017 Oct 11;96(2):402-413.e5. doi: 10.1016/j.neuron.2017.09.020. PMID: 29024663.
Bigio B, Mathé AA, Sousa VC, Zelli D, Svenningsson P, McEwen BS, Nasca C. Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance. Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7906-11. doi: 10.1073/pnas.1603111113. Epub 2016 Jun 27. PMID: 27354525; PMCID: PMC4948346.
- Commentary in Post RM. Myriad of implications of acetyl-l-carnitine deficits in depression. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8475-8477.