Faculty

Pioneering Rehabilitation

Camille Brochier, Ph.D.

Instructor, Neuronal Epigenetics

Instructor in Neuroscience, Brain and Mind Research Institute

Weill Cornell Medical College

Phone:

(914) 368-3152

Research Focus

The main focus of my scientific interest is to prevent, treat and cure neurodegeneration.  Understanding the molecular events that determine a neuron's fate following injury or during disease is key to finding efficient therapeutic approaches.

During my training as a graduate student in Dr. Jean-Marc Elalouf’s laboratory (Paris XI University, France), I used transcriptomic (Serial Analysis of Gene Expression) and histological techniques to identify genes that exhibit a regionalized expression pattern in the mouse and human brain, and are deregulated in neuropathological conditions.  Pursuing my interest in gene deregulation linked to neuronal disease, I joined Dr. Brett Langley’s laboratory at The Burke Medical Research Institute as a post-doctoral fellow in order to study the role of histone deacetylases (HDAC) in DNA damage-induced neurodegeneration.  We demonstrated that the neuroprotective efficacy of HDAC inhibitors could be attributed to their ability to modify the specific acetylation pattern of the tumor suppressor protein p53, which is a major regulator of gene expression during neuronal death.  Our observations led us to explore the connection between HDAC activity and DNA repair in neurons, which is currently being investigated. 

Biography

B.Sc. Molecular Biology
Paris XI University, France

M.Sc. Molecular Biology, Genomics
Paris XI University, France

Ph.D. Molecular Biology, Genomics
Paris XI University, France
Atomic Energy Commission (CEA), France

Postdoctoral Fellow
The Burke Medical Research Institute, White Plains, NY
Weill Cornell Medical College, New York, NY

Publications

Brochier C and Langley B. 2013. Chromatin modifications associated with DNA double strand breaks repair as potential targets for neurological diseases. Neurotherapeutics, 10(4):817-30. DOI 10.1007/s13311-013-0210-9.

Brochier C, Dennis G, Rivieccio MA, McLaughlin K, Coppola G, Ratan RR, Langley B. 2013. Specific Acetylation of p53 by HDCA Inhibition Prevents DNA Damage-Induced Apoptosis in Neurons. J Neurosci, 33(20): 8621-32

Butler KV, Kalin Jay, Brochier C, Vistoli G, Langley B, and Kozikowski AP. 2010. Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A. 2010. J. Am. Chem. Soc, 132(31): 10842-6 

Rivieccio MA, Brochier C, Willis DE, Walker BA, D’Annibale MA, McLaughlin K, Siddiq A, Kozikowski AP, Jaffrey SR, Twiss JL,Ratan RR, Langley B. 2009. HDAC6 is a target for protection and regeneration following injury in the nervous system. PNAS, 106(46): 19599-604

Langley B, Brochier C, Rivieccio MA. 2009. Targeting Histone Deacetylases as a Multifaceted Approach to Treat the Diverse Outcomes of Stroke. Stroke, 40(8): 2899-905.

Brochier C, Gaillard MC, Diguet E, Caudy N, Dossat C, Segurens B, Wincker P, Roze Emmanuel, Caboche J, Hantraye P, Brouillet E, Elalouf JM, and de Chaldée M. 2008. Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models. Physiol Genomics, 33(2): 170-9.

de Chaldée M, Brochier C, Van de Vel A, Caudy N, Luthi-Carter R, Gaillard MC, Elalouf JM. 2006. Capucin: a novel striatal marker down-regulated in rodent models of Huntington disease. Genomics, 87(2): 200-7.


Citations via Google Scholar

Current Projects

Role of Acetylation in Neuronal DNA Repair

One of the most critical processes fundamental to cellular function, integrity, and indeed, survival, is the appropriate response to and repair of DNA damage that arises from normal aspects of DNA metabolism, endogenous sources such as reactive oxygen species, or exogenous genotoxic agents such as mutagens and ionizing radiation. Double strand breaks (DSBs) are the most genotoxic DNA lesions. Unrepaired DSBs can lead to cell death, whereas misrepaired DSBs increase the likelihood of chromosome rearrangement, mutagenesis and loss of crucial genetic information. In replicating cells, such instability can result in apoptosis or cellular transformation. In the case of neurons residing in the adult brain, this is even more critical, given that they are post-mitotic and terminally differentiated, and cannot be readily replaced after trauma or disease.  Indeed, accumulation of genomic (and mitochondrial) DNA damage is an important feature of both acute and chronic neurodegeneration.

A significant body of evidence suggests that histone acetylation, which is regulated by the concerted actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), plays a central role in the chromatin remodeling that occurs in response to DNA damage. Chromatin-modifying drugs such as HDAC inhibitors (HDACis) have emerged as attractive therapeutic compounds for neurodegeneration in the last decade. Nevertheless, more studies are needed to determine the effect of HDACis on DNA damage repair in neurodegeneration.

One limitation in understanding DNA repair in neurons, is that most of what is known comes from studies performed in cycling cells or tumors, and might be therefore irrelevant to post-mitotic cells. One of our goals in the Langley laboratory is to study the molecular mechanisms specific to neuronal DNA repair and the effects of HDAC inhibition in neurons, which is crucial for the development of efficient neurotherapeutic strategies.