Anne E. Chiaramello

Education

BS, University of Nice-Sophia Antipolis, Nice, 1983

MS, San Diego State University, 1986

PhD, University of California, San Diego, 1990

Biography

Professional Experience

2017-present: Director of the Mito-EpiGen Program
2003-2016: Academic Coordinator of the Institute for Biomedical Sciences
2013-2016: Founding Director of the pre-medicine enhancer graduate programs in Anatomical and Translational Sciences (GCATS and MATS)
2008-2018: Concentration advisor for the Neurosciences and Pharmacology/Physiology tracks of the Institute for Biomedical Sciences

Institutes and Graduate Program Affiliations

GW Institute for Biomedical Sciences
GW Institute for Neuroscience
Molecular Medicine Graduate Program
Biochemistry and Systems Biology Graduate Program

Expertise

Mitochondrial Diseases
Mitochondrial Biology
Neurotherapeutics and Drug Development
Neuronal Transcriptional and Epigenetic Regulation

Research

The Chiaramello lab has two main research projects. The basic research project focuses on mitochondrial biology and neurodevelopment, while the translational research project aims at designing novel therapeutic approaches for incurable mitochondrial diseases.

One of our goals is to understand how the neurogenic basic helix-loop-helix transcriptional factor NeuroD6 links neuronal differentiation to survival during neurogenesis. The gene set enrichment analysis of our genome-wide microarray studies has revealed a link between NeuroD6 and a cluster of mitochondrial biogenic and bioenergetic genes. Furthermore, our functional studies highlighted neuronal-specific regulation of mitochondrial biogenesis, an area that has remained largely unexplored. More specifically, we made three substantial findings: 1) NeuroD6 plays an integrative role in coupling mitochondrial biogenesis with the early stages of neuronal differentiation, the timing of which is critical for proper neuritogenesis; 2) NeuroD6 increases the mitochondrial bioenergetic capacity of neuronal progenitors, thereby conferring tolerance to mitochondrial stressors known to affect neural development; and 3) small-molecule drugs induce mitochondrial biogenesis and metabolic remodeling in differentiating neuronal cells and embryonic mouse brains.

Our findings on mitochondrial biogenesis and energy metabolism have shifted our goals toward translational research, with the chief objective to investigate a novel therapeutic approach for patients affected with the incurable mitochondrial disorder MELAS. Currently, no therapeutic options are available to patients affected with MELAS. The cardinal hallmark of this fatal neurodegenerative disease is a chronic energy deficit due to mutations in the mitochondrial genome, resulting in mitochondrial dysfunction. Despite our better understanding of the pathogenesis and diagnosis of MELAS, no pharmacological agents can mitigate the ATP deficit and stop the fatal progression of this disease. Presently, we are collaborating with Dr. Gropman, a pediatrician and neurologist specializing in mitochondrial disorders at our affiliated Children’s National Health System. Using fibroblasts derived from skin biopsies performed on MELAS patients, we screen a battery of small molecule drugs to identify the most promising pharmacological agents to rectify mitochondrial dysfunction and to mitigate the chronic energy deficit.

Our NINDS-funded study will advance our understanding of the molecular pathogenesis of MELAS. Our collaborative pre-clinical studies with Children’s National Health System and its Center for Translational Research lay the foundation for clinical studies to evaluate the therapeutic value of the most promising candidates on MELAS patients. Our ultimate goal is to combine translational research with personalized medicine to alleviate the debilitating symptoms of MELAS and other mitochondrial disorders.

Teaching

MMED 8282 Neural Development and Neurodevelopmental Disorders (graduate students)
ANAT 6182 Fundamentals of Translational Sciences (graduate students)
ANAT 213 Human Microscopic Anatomy (medical students)

Publications

Uittenbogaard, M., Wang H., Zhang V.W., Wong, L.J., Brantner, C.A., Gropman, A., and Chiaramello, A. 2019. The nuclear background influences the penetrance of the near-homoplasmic m.1630 A>G MELAS variant in a symptomatic proband and asymptomatic mother. Mol Genet Metab. In Press, doi: 10.1016/j.ymgme.2019.01.022
Uittenbogaard, M., Brantner, C.A., Fang, Z., Wong, L.J., Gropman, A., and Chiaramello, A. 2018. The m.11778 A>G variant associated with the coexistence of Leber’s hereditary optic neuropathy and multiple sclerosis-like illness dysregulates the metabolic interplay between mitochondrial oxidative phosphorylation and glycolysis. Mitochondrion. In press, doi.org/10.1016/j.mito.2018.06.001
Uittenbogaard, M., Gropman, A., Brantner, C.A., and Chiaramello, A. 2018. Novel metabolic signature of compounds heterozygous Szt2 variants in a case of early onset of epileptic encephalopathy. Clin Case Rep. 6: 2376-2384
Gropman, A., and Chiaramello, A. 2018. Phenotypic spectrum of maternally inherited Leigh Syndrome associated with the m.8993 T>G. variant. Mol. Genet. Metab. Rep. 15: 134
Uittenbogaard, M., Brantner, C.A., Fang, Z., Wong, L.J., Gropman, A., and Chiaramello, A. 2018. Novel insights into the functional metabolic impact of an apparent de novo m.8993 T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome. Mol. Genet. Metab. 124: 71-81.
Uittenbogaard, M., Brantner, C.A., and Chiaramello, A. 2018. Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells. Cell Death Dis. 9: 360. doi: 10.1007/s00418-015-1388-1. Featured in Neural Cell News
Uittenbogaard, M., and Chiaramello, A. 2016. Novel subcellular localization of the DNA helicase Twinkle at the kinetochore complex during mitosis in neuronal-like progenitor cells. Histochem Cell Biol. 145: 275-286. Featured on the Cover Issue.
Uittenbogaard, M., and Chiaramello, A. 2015. Mitochondrial respiratory disorders: a perspective on their metabolite biomarkers and implications for clinical diagnosis and therapeutic intervention. Biomark. J. 1(1). Pii:1.
Uittenbogaard, M., and Chiaramello, A. (2014) Mitochondrial biogenesis: a therapeutic target for neurodevelopmental disorders and neurodegenerative diseases. Invited Review. Curr. Pharm. Des. 20: 5574-5593
Baxter, K.K., Uittenbogaard, M., and Chiaramello, A. (2012) The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone. Exp. Cell Res. 318: 2200-2214.
Uittenbogaard, M., Baxter, K.K., and Chiaramello, A (2010) The neurogenic basic helix-loop-helix transcription factor NeuroD6 confers tolerance to oxidative stress by triggering an antioxidant response and sustaining the mitochondrial biomass. ASN NEURO 2(2): e00034.
Uittenbogaard, M., Baxter, K.K., and Chiaramello, A. (2010) NeuroD6 genomic signature bridging neuronal differentiation to survival via the molecular chaperone network. J. Neurosci. Res. 88: 33-54.
Uittenbogaard, M., Baxter, K.K., and Chiaramello, A. (2009) Cloning and characterization of the 5’UTR of the rat anti-apoptotic Bcl-w gene. Biochem. Biophys. Res. Commun. 389: 657-662.
Baxter, K.K., Uittenbogaard, M., and Chiaramello, A. (2009) The neurogenic basic helix-loop-helix transcription factor NeuroD6 concomitantly increases mitochondrial mass and regulates cytoskeletal organization in the early stages of neuronal differentiation. ASN NEURO 1(4): e00016.
Uittenbogaard, M., Martinka, D.L., Johnson, P.F., Vinson, C., and Chiaramello, A. (2007). 5’UTR of the neurogenic bHLH Nex1/MATH-2/NeuroD6 gene is regulated by two distinct promoters through CRE and C/EBP binding sites. J. Neurosci. Res. 85: 1-18.
Uittenbogaard, M., and Chiaramello, A. (2005). The basic helix-loop-helix transcription factor Nex1/MATH-2 promotes neuronal survival of PC12 cells by modulating the dynamic expression of anti-apoptotic and cell cycle regulators. J. Neurochem. 92: 585-596.
Uittenbogaard, M., and Chiaramello, A. (2004) Expression profiling upon Nex1/MATH-2-mediated neuritogenesis in PC12 cells and its implication in regeneration. J. Neurochem. 91: 1332-1343.
Uittenbogaard, M., Martinka, D.L., and Chiaramello, A. (2003). The basic helix-loop-helix differentiation factor Nex1/MATH-2 functions as a key activator of the GAP-43 gene. J. Neurochem. 84: 678-688.
Uittenbogaard, M., and Chiaramello, A. (2002) Expression of the bHLH transcription factor Tcf12 (ME1) gene is linked to the expansion of precursor cell populations during neurogenesis. Brain Res. Expr. Patterns 1: 115-121.
Uittenbogaard, M., and Chiaramello, A. (2002) Constitutive expression of the basic helix-loop-helix Nex1/MATH-2 transcription factor promotes neuronal differentiation of PC12 cells and neurite regeneration. J. Neurosci. Res. 67: 235-245.