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Science at the Center - Research
Kamal Sharma, Ph.D.
Assistant Professor, Department of Neurobiology, Pharmacology and Physiology
Research Relevant to Peripheral Neuropathy
Our research efforts are focused on understanding the spinal motor circuits. These circuits include motor neurons and spinal sensory neurons that project into the peripheral nerves and innervate different muscles in the body. These neurons and their axons are the primary target of many demyelinating and neurodegenerative diseases.
We are particularly intrigued by the observation that in most patients, the disease affects only some neurons and nerves. This observation suggests that many neurons are naturally resistant to pathological changes following insult. Molecular biology provides powerful tools to understand selective vulnerability and also natural resistance of different neurons to the disease causing agents. Dr. Hiroshi Yajima, a postdoctoral fellow in the laboratory, is using molecular and genetic techniques to study a relatively large gene family. These recently discovered molecules are called protocadherins. Hiroshi has developed reagents to study mRNA and protein expression of 36 members of this gene family. Hiroshi and an undergraduate student, Ms. Anushka Hauner, have found that these proteins are expressed in subsets of neurons in the spinal cord and the sensory ganglia. We are particularly encouraged by the observation that these proteins are highly concentrated in axons and dendrites of neurons in adult mice. With technical help from Ms. Aida Pourbovali and Charity Goodman, we are currently testing whether these proteins are important for motor and sensory functions of the spinal cord.
K. Sharma, Z. Korade and E. Frank. (1994) Central projections of sensory axons wait for development of guidance cues in the spinal cord. Development 120:1315-1323.
K. Sharma, Z. Korade and E. Frank. (1995) Late-migrating neuroepithelial cells from the spinal cord differentiate into sensory ganglion cells and melanocytes. Neuron 14:143-152.
K. Sharma, and E. Frank. (1998) Sensory axons are guided by local cues in the developing dorsal spinal cord. Development 125:635-643.
N. Takuma, H.Z. Sheng, Y. Furuta, J.M. Ward, K. Sharma, B.L.M. Hogan, S.L. Pfaff, H. Westphal, S. Kimura and K.A. Anderson (1998) Formation of Rathke's pouch requires dual induction from the diencephalon. Development 125:635-643.
K. Sharma, H.Z. Sheng, K. Lettieri, H. Li, A. Karavanov, S. Potter, H. Westphal and S.L. Pfaff. (1998) LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell 95:817-828.
J. Thaler, K. Harrison, K. Sharma, K. Lettieri, J. Kerl and S.L. Pfaff: (1999). Appropriate motor neuron specification and axon pathfinding is dependent on homeodomain factor HB9: A repressor of interneuron identity. Neuron 23:675-687.
K. Sharma, A.E. Leonard, K. Lettieri and S.L. Pfaff. (2000). Genetic and Epigenetic Mechanisms Contribute to Motor Neuron Pathfinding. Nature 406:515-519.
Fu, S.Y, Sharma, K., Luo Y., Raper J.A., Frank E. (2000). Sema3A regulate developing sensory projections in the chicken spinal cord. Journal of Neurobiology 45:227-236.
Kamal Sharma and Juan Carlos Ipisuza Belmonte (2001) Development of the limb neuromuscular system, Current Opinions in Cell Biology 13:204-210.
Kamal Sharma and Chian-Yu Peng (2001) Spinal motor circuits: Merging Development and Function. Neuron 29:321-324.
Lance-Jones, C. Omelchenlco, N, Bailis, A., Lynch, S., and Sharma, K. (2001). Hoxd-10 induction and regionalization in the developing lumbosacral spinal cord. Development 128:2255-2268.
For more information about research in the Sharma lab please visit their web site: http://sharmalab.bsd.uchicago.edu/