ASU SoLS Faculty: Lei Lei

How are neurons generated? How do they form specific neural circuits? How are they regulated? These are the big questions that our group is focusing on studying using transgenic and tissue-specific conditional knockout mice as a model system.

The human brain has over 100 billion neurons and 100 trillion interneuronal connections, termed "synapses". Most of these neurons are generated from multi-potent neural stem cells during embryogenesis, but new neurons are continuously generated from adult neural stem cells everyday throughout our lives, albeit at a much reduced rate. Neurons form specific neural circuits and control the function of the rest of our body including physiological, psychological, and cognitive functions.

The formation of human brain is a complex and delicate process. It is well recognized that subtle alterations in neural circuitry during critical periods in brain development (such as prenatal, neonatal, childhood, and adolescence) underlie the etiologies of many neuropsychiatric disorders. More severe brain malformations could lead to birth defects or cancers. My research group studies how neurons and neural circuits are generated in mammalian brains using transgenic, knockout, and conditional knockout mice. Through detailed analysis of these genetically engineered mice using molecular, cellular, imaging, and behavioral approaches, we have gained fundamental insights into how neurons and neural circuits are formed and how this complicated process is regulated. A thorough understanding of brain development has important therapeutic implications in treating neurological disorders and neurodegenerative diseases.

In the peripheral nervous system, primary sensory neurons located in the dorsal root ganglion (DRG) and trigeminal ganglion are responsible for transducing the stimulation of touch, temperature, pain, and information of limb placement and body position into the spinal cord, where information is relayed to higher centers in the brain. A subset of sensory neurons, termed nociceptive neurons, is responsible for pain and temperature. Our lab is also interested in understanding the specification and diversification of these neurons, with the hope that our research may lead to the identification of novel analgesics for managing pain, a major clinical problem.

For ASU undergraduate students, my laboratory is always interested in talented and motivated students, including but not limited to, MARC and SOLUR students. I am also interested in students who would like to pursue honor theses research in my laboratory.

For prospecting graduate students, I am a faculty member of the newly launched Interdisplinary Graduate Program in Neuroscience established between ASU and the Barrow Neurological Institute (BNI) in Phoenix. I am also a faculty member of the graduate programs in Molecular and Cell Biology (MCB) and Biology at ASU. Strong candidates are encouraged to contact me or the Graduate Program office ( http://sols.asu.edu/grad/index.php ).

Selected Publications

Romero, M., Lin, L., Lush, M., Lei, L ., Parada, L.F., and Zhu, Y. (2007). Deletion of NF1 in neurons induces increased axon collateral branching after dorsal root injury. Journal of Neuroscience 27, 2124-2134.

Lei, L., Zhou, J., Lin, L., and Parada, L.F. (2006). Brn3a and Klf7 cooperate to control TrkA expression in sensory neurons. Developmental Biology 300, 758-769.

Lei, L., Laub, F., Lush, M., Romero, M., Zhou, J., Luikart, B., Klesse, L., Ramirez, F., and Parada, L.F. (2005). The zinc finger transcription factor Klf7 is required for TrkA gene expression and development of nociceptive sensory neurons.Genes & Development 19, 1354-1364.

Laub, F., Lei, L., Sumiyoshi, H., Kajimura, D., Dragomir, C., Smaldone, S., Puche, A.C., Petros, T.J., Mason, C., Parada, L.F., and Ramirez, F. (2005). Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. Molecular and Cellular Biology 25, 5699-5711.

Ma, L.,Lei, L., Eng, S.R., Turner, E., and Parada, L.F. (2003). Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons. Development 130, 3525-3534.

Lei, L., Ma, L., Nef, S., Thai, T., and Parada, L.F. (2001) mKlf7, a potential transcriptional regulator of trkA nerve growth factor receptor expression in sensory and sympathetic neurons. Development 128, 1147-1158

Lei, L., Ren, D., and Burton, Z.F. (1999). The RAP74 subunit of human transcription factor IIF has similar roles in initiation and elongation. Molecular and Cellular Biology 19, 8372-8382

Ren, D., Lei, L., and Burton, Z.F. (1999). A region within the RAP74 subunit of human transcription factor IIF is critical for initiation but dispensable for complex assembly. Molecular and Cellular Biology 19, 7377-7387

Lei, L., Ren, D., Finkelstein, A., and Burton, Z.F. (1998). Functions of the N- and C-terminal domains of human RAP74 in initiation, elongation, and recycling of RNA polymerase II. Molecular and Cellular Biology 18, 2130-2142

Wang, B.Q., Lei, L., and Burton, Z.F. (1994). Importance of codon preference for production of human RAP74 and reconstitution of the RAP30/74 complex. Protein Expression and Purification 5, 476-485

Reviews
Lei, L.* and Parada, L.F. (2007) Transcriptional regulation of Trk family neurotrophin receptors. Cellular and Molecular Life Sciences 64, 1-11.*, Corresponding author.