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Charlotte Sumner, MD

Department Affiliations Neurology and Neuroscience
Rank Associate Professor
Office Phone 410-502-6685
Lab Phone 410-502-6467
Fax 410-502-5459
SOM Address 246 Rangos
Sumner Lab

Will Aisenberg 2014

Research Interests

The goal of our laboratory is to determine the genetic and molecular mechanisms of neurodegenerative disorders of motor neurons and peripheral nerves. Spinal muscular atrophies (SMAs) and various forms of Charcot-Marie-Tooth disease (CMT) are among the most common inherited neurological disorders and cause progressive weakness of muscle, sensory loss, and often, early mortality. Currently, there are no disease-modifying therapies to offer patients. Our research aims are: 1) to genetically characterize these diseases, 2) to investigate molecular and cellular mechanisms of disease pathogenesis, and 3) to develop novel therapeutic strategies. Some of our ongoing research projects are:

Identifying novel genetic causes of SMAs and CMTs In order to further understand both normal motor neuron and peripheral nerve biology and pathological events that cause neuronal degeneration, we aim to identify the genetic causes of SMAs and CMTs in families with novel phenotypes. We recently identified mutations in the transient receptor vanilloid 4 gene (TRPV4) in patients with CMT2C and distal SMA. TRPV4 encodes a cation channel and the disease-associated mutations cause a gain of channel function. We are currently studying cellular, drosophila, and mouse models of this disorder.
Investigating the molecular and cellular mechanisms of SMAs A major focus of our work is the autosomal recessive motor neuron disease proximal SMA, the most common inherited cause of infant mortality. SMA is caused by mutation of the survival motor neuron 1 (SMN1) gene, retention of the SMN2 gene, and deficiency of the SMN protein. The SMN protein plays an essential role in synthesizing small nuclear ribonuclear proteins (snRNPs), which are critical components of the spliceosome. In order to understand how SMN protein deficiency causes motor neuron dysfunction and degeneration, we study the molecular, cellular, and physiological events during disease pathogenesis in SMA mice and human tissues.
Developing therapies for SMAs All patients with proximal SMA retain one or more copies of the SMN2 gene. When this gene is expressed at sufficient levels, it can prevent SMA disease manifestations. Thus a principal goal of our therapeutics development efforts is to identify small molecules that activate SMN2 expression. We studying SMN-inducing compounds that are being developed for the treatment of SMA patients.


Bosch-Marce M, Wee CD, Martinez TL, Lipkes CE, Choe DW, Kong L, Van Meerbeke JP, Musaro A, Sumner CJ. Increased IGF-1 in muscle modulates the phenotype of severe SMA mice. Human Molecular Genetics 2011;33:1733-41.

Mentis GZ, Liu W, Blivis D, Drobac E, Crowder ME, Kong L, Alvarez FJ, Sumner CJ, O’Donovan MJ. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy. Neuron 2011; 1):453-467.

Landouré G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nature Genetics 2010;42:170-4.

Kong L, Wang X, Choe DW, Polley M, Bosch- Marcé, Griffin JW, Rich MM, Sumner CJ. Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice. Journal Neuroscience 2009;29:842-51.

Avila AM, Burnett BB, Taye AA, Gabenella F, Knight M, Hartenstein P, Cizman Z, DiProspero NA, Fischbeck KH, Sumner CJ. Trichostatin A increases SMN expression and survival in spinal muscular atrophy mice. Journal Clinical Investigation 2007;117:659-71.

Levy J,* Sumner CJ,* Tokito M, Ligon LA, LaMonte B, Wallace KE, Harmison G, Puls I, Fischbeck KH, Holzbaur, ELF. A G59S dynactin mutation that causes motor neuron degeneration induces loss of function and protein aggregation. Journal Cell Biology 2006;172:733-745. (*The first two authors contributed equally to this study)