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Afonso C. Silva, PhD
- Endowed Chair Professor of Translational Neuroimaging, Neurobiology
Education & Training1990 BS, MS, Universidade Federal de Pernambuco, Recife, Brazil 1996 PhD Carnegie Mellon University, Pittsburgh, PA
6065 Biomedical Science Tower 3
Research Interest Summary
Anatomical and functional imaging of the marmoset brain; cerebrovascular disease and Alzheimer’s disease; genetic engineering.
We are interested in using a combination of behavioral, electrophysiological and imaging techniques to understand the mechanisms of neurovascular coupling that maintain a tight relationship between neuronal activity and cerebral blood flow. This relationship is crucial for the brain, and its disruption leads to dysfunction and disease. Our main research interests are in understanding mechanisms of cerebrovascular dysfunction as a common cause of several neurodegenerative diseases. We have extensive experience in the development and application of multimodal neuroimaging methods to study the brain’s anatomy and function, and our laboratory works with genetically engineered marmoset models of brain diseases, including stroke, Alzheimer’s disease and multiple sclerosis. Our expertise is in the development of functional neuroimaging methods to understand (1) how the cerebral microvasculature reacts, in space and in time, to changes in neuronal activity; and (2) to understand how the mechanisms of neurovascular coupling are disrupted in neurological disorders.
On theme 1, we focus on understanding how the spatial localization and temporal evolution of the hemodynamic response to functional brain stimulation relate to the cortical cytoarchitecture. We use fMRI and optical imaging methods to probe the functional response to focal neuronal activity. Much of this was initiated in rodents, but has been ported to marmosets, a nonhuman primate with great promise as an animal model in biomedical research. We have been extremely productive in our work with marmosets (34 manuscripts published in the past 10 years), spanning from fMRI, to two-photon optical microscopy, to detailed MRI description of the rich anatomical details of the marmoset brain, to manuscripts on marmoset models of multiple sclerosis and transgenic and genetically engineered marmosets. We developed transgenic marmosets that express the genetically encoded calcium indicator molecule GCaMP6 that will constitute a much-improved animal model for studying neurovascular coupling in relevant conditions. These animals are the first transgenic marmosets produced outside Japan, the only transgenic marmosets present in the USA, and are currently in F1 generation and ready to be studied with two-photon laser scanning microscopy.
On theme 2, we are interested in understanding how the mechanisms of CBF regulation are altered by pathological brain states, including stroke and Alzheimer’s disease. We developed a genetically engineered marmoset model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), the most frequent of the genetic small vessel diseases. Data obtained from marmosets are likely to offer new insights into the molecular and genetic mechanisms of neurological disorders, and potentially contribute to the development of novel biomarkers and therapeutical approaches with higher translational impact.
Lee NJ, Ha SK, Sati P, Absinta M, Nair G, Luciano NJ, Leibovitch EC, Yen CC, Rouault TA, Silva AC, Jacobson S, Reich DS. Potential role of iron in repair of inflammatory demyelinating lesions. J Clin Invest. 2019 Oct 1;129(10):4365-4376. doi: 10.1172/JCI126809. PubMed PMID: 31498148; PubMed Central PMCID: PMC6763243.
Choi SH, Mou Y, Silva AC. Cannabis and Cannabinoid Biology in Stroke. Stroke. 2019 Sep;50(9):2640-2645. doi: 10.1161/STROKEAHA.118.023587. Epub 2019 Aug 1. PubMed PMID: 31366312; PubMed Central PMCID: PMC6713285.
Liu C, Yen CC, Szczupak D, Ye FQ, Leopold DA, Silva AC. Anatomical and functional investigation of the marmoset default mode network. Nat Commun. 2019 Apr 29;10(1):1975. doi: 10.1038/s41467-019-09813-7. PubMed PMID: 31036814; PubMed Central PMCID: PMC6488610.
Lefeuvre JA, Guy JR, Luciano NJ, Ha SK, Leibovitch E, Santin MD, Silva AC, Jacobson S, Lehéricy S, Reich DS, Sati P. The spectrum of spinal cord lesions in a primate model of multiple sclerosis. Mult Scler. 2019 Feb 7:1352458518822408. doi: 10.1177/1352458518822408. PubMed PMID: 30730246; PubMed Central PMCID: PMC6685769.
Park JE, Silva AC. Generation of genetically engineered non-human primate models of brain function and neurological disorders. Am J Primatol. 2019 Feb;81(2):e22931. doi: 10.1002/ajp.22931. Epub 2018 Dec 26. Review. PubMed PMID: 30585654; PubMed Central PMCID: PMC6463491.
Leibovitch EC, Caruso B, Ha SK, Schindler MK, Lee NJ, Luciano NJ, Billioux BJ, Guy JR, Yen C, Sati P, Silva AC, Reich DS, Jacobson S. Herpesvirus trigger accelerates neuroinflammation in a nonhuman primate model of multiple sclerosis. Proc Natl Acad Sci USA. 2018 Oct 30;115(44):11292-11297. doi: 10.1073/pnas.1811974115. Epub 2018 Oct 15. PubMed PMID: 30322946; PubMed Central PMCID: PMC6217390.
Lee NJ, Ha SK, Sati P, Absinta M, Luciano NJ, Lefeuvre JA, Schindler MK, Leibovitch EC, Ryu JK, Petersen MA, Silva AC, Jacobson S, Akassoglou K, Reich DS. Spatiotemporal distribution of fibrinogen in marmoset and human inflammatory demyelination. Brain. 2018 Jun 1;141(6):1637-1649. doi: 10.1093/brain/awy082. PubMed PMID: 29688408; PubMed Central PMCID: PMC5972667.
Choi SH, Arai AL, Mou Y, Kang B, Yen CC, Hallenbeck J, Silva AC. Neuroprotective Effects of MAGL (Monoacylglycerol Lipase) Inhibitors in Experimental Ischemic Stroke. Stroke. 2018 Mar;49(3):718-726. doi: 10.1161/STROKEAHA.117.019664. Epub 2018 Feb 13. Erratum in: Stroke. 2018 Sep;49(9):e294. PubMed PMID: 29440474; PubMed Central PMCID: PMC5829008.
Hirano Y, Yen CC, Liu JV, Mackel JB, Merkle H, Nascimento GC, Stefanovic B, Silva AC. Investigation of the BOLD and CBV fMRI responses to somatosensory stimulation in awake marmosets (Callithrix jacchus). NMR Biomed. 2018 Mar;31(3). doi: 10.1002/nbm.3864. Epub 2017 Dec 29. PubMed PMID: 29285809; PubMed Central PMCID: PMC5841465.
Liu C, Ye FQ, Yen CC, Newman JD, Glen D, Leopold DA, Silva AC. A digital 3D atlas of the marmoset brain based on multi-modal MRI. Neuroimage. 2018 Apr 1;169:106-116. doi: 10.1016/j.neuroimage.2017.12.004. Epub 2017 Dec 5. PubMed PMID: 29208569; PubMed Central PMCID: PMC5856608.
Yen CC, Papoti D, Silva AC. Investigating the spatiotemporal characteristics of the deoxyhemoglobin-related and deoxyhemoglobin-unrelated functional hemodynamic response across cortical layers in awake marmosets. Neuroimage. 2018 Jan 1;164:121-130. doi: 10.1016/j.neuroimage.2017.03.005. Epub 2017 Mar 6. PubMed PMID: 28274833; PubMed Central PMCID: PMC5587354
Toarmino CR, Yen CCC, Papoti D, Bock NA, Leopold DA, Miller CT, Silva AC. Functional magnetic resonance imaging of auditory cortical fields in awake marmosets. Neuroimage. 2017 Nov 15;162:86-92. doi: 10.1016/j.neuroimage.2017.08.052. Epub 2017 Aug 19. PubMed PMID: 28830766; PubMed Central PMCID: PMC5705576.
Silva AC. Anatomical and functional neuroimaging in awake, behaving marmosets. Dev Neurobiol. 2017 Mar;77(3):373-389. doi: 10.1002/dneu.22456. Epub 2016 Oct 21. Review. PubMed PMID: 27706916; PubMed Central PMCID: PMC5318267.
Papoti D, Yen CC, Hung CC, Ciuchta J, Leopold DA, Silva AC. Design and implementation of embedded 8-channel receive-only arrays for whole-brain MRI and fMRI of conscious awake marmosets. Magn Reson Med. 2017 Jul;78(1):387-398. doi: 10.1002/mrm.26339. Epub 2016 Aug 8. PubMed PMID: 27501382; PubMed Central PMCID: PMC5298952.
Park JE, Zhang XF, Choi SH, Okahara J, Sasaki E, Silva AC. Generation of transgenic marmosets expressing genetically encoded calcium indicators. Sci Rep. 2016 Oct 11;6:34931. doi: 10.1038/srep34931. PubMed PMID: 27725685; PubMedCentral PMCID: PMC5057151.
Santisakultarm TP, Kersbergen CJ, Bandy DK, Ide DC, Choi SH, Silva AC. Two-photon imaging of cerebral hemodynamics and neural activity in awake and anesthetized marmosets. J Neurosci Methods. 2016 Sep 15;271:55-64. doi:10.1016/j.jneumeth.2016.07.003. Epub 2016 Jul 5. PubMed PMID: 27393311; PubMed Central PMCID: PMC5003758.
Miller CT, Freiwald WA, Leopold DA, Mitchell JF, Silva AC, Wang X. Marmosets: A Neuroscientific Model of Human Social Behavior. Neuron. 2016 Apr 20;90(2):219-33. doi: 10.1016/j.neuron.2016.03.018. Review. PubMed PMID: 27100195; PubMed Central PMCID: PMC4840471.
Yu X, He Y, Wang M, Merkle H, Dodd SJ, Silva AC, Koretsky AP. Sensory and optogenetically driven single-vessel fMRI. Nat Methods. 2016 Apr;13(4):337-40. doi: 10.1038/nmeth.3765. Epub 2016 Feb 8. PubMed PMID: 26855362; PubMed Central PMCID: PMC6298439.