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Chris Li

Chris Li

Biology

Developmental neurobiology


Email:
Office Phone: (212) 650-8450

Education:

  1. Ph.D., Harvard University
  2. M.S., Columbia University
  3. A.B., Barnard College, Columbia University

Biography:

Programs: Neuroscience (NS), Molecular, Cell, and Developmental Biology (MCD), Biochemistry 
Office: Marshak J718, 212-650-8450
Lab: Marshak J721, 212-650-8533

Laboratory personnel:
Graduate Students: Collin Ewald, Pei Zhao, Adanna Alexander
Master's Student: Ingrid Buntschuh
Undergraduate Students: Ivor Joseph, Lana Tolen, Ruby Cheng, Aysha Islam, Jain Mathew, Maisam Begum
Technician: Dan Raps

 

Research:
My lab uses molecular genetic approaches to address two questions in neurobiology.  In our first project, we are interested in how different neurotransmitters affect the behavior of an organism.  We are using the nematode Caenorhabditis elegans as our model system and have focused on examining the role of a specific class of neurotransmitter, the neuropeptides.  We are interested in the family of FMRFamide-related peptides, which have been implicated in pain modulation in mammals.  At least 31 genes encode FMRFamide-related peptides, or FLPs, in C. elegans.  To understand the role of the different flp genes, we have begun the task of determining the expression pattern and knocking out each flp gene.  Although there is functional overlap between the genes, inactivation of certain flp genes leads to behavioral defects, including defects in movement, reproduction, oxygen response, and fat accumulation.  Insights into the role of the flp genes may reveal how neuropeptides are used in mammalian systems as well as in parasitic nematodes, which infect over one billion people worldwide. 
In a second project, we are using C. elegans as a model to examine genes implicated in neurodegenerative disorders.  Mutations in the human APP gene have been linked to familial Alzheimer's Disease.  The functions of APP and APP-related genes in humans, however, are unclear.  C. elegans contains one APP-related gene, apl-1, which encodes a protein that is highly similar to human APP.  apl-1 has an essential function in C. elegans.  Loss of apl-1 disrupts several developmental processes, including molting and morphogenesis, and results in larval lethality.  Expression of the extracellular domain of APL-1 is sufficient to rescue the apl-1 lethality, suggesting that apl-1 acts non-cell autonomously as a signaling molecule.  Overexpression of APL-1 also causes several phenotypes, including an incompletely penetrant lethality, suggesting that levels of APL-1 need to be tightly regulated to ensure the animal’s viability.  We are examining the role of apl-1 and identifying the genes that act in the same pathway as apl-1.  Although different organisms may use APP and related proteins in different functional contexts, the pathways in which they function and the molecules with which they interact are likely to be conserved.  Hence, identification of pathways relevant to APL-1 may provide insights into the roles and cellular pathways of human APP.

Recent publications:
Rogers, C., V. Reale, K.Kim, H. Chatwin, C. Li, P. Evans, and M. de Bono (2003) Inhibition of social feeding in C. elegans by FMRFamide-related peptide activation of the NPR-1 receptor.  Nature Neurosci. 6:1178-1185.
Lints, R., L. Jia, K. Kim, C. Li, and S.W. Emmons (2004) Specification of sensory organ identity by selector genes in C. elegans.  Dev. Biol. 269:137-151.
Kim, K, and C. Li (2004) Differential expression and regulation of flp neuropeptide genes in C. elegans.  J. Comp. Neurol.  475:540-550.
Zhao, J., K.L. Townsend, L.C. Schulz, T.H. Kunz, C. Li, E.P. Widmaier (2004) Leptin receptor expression increases in placenta, but not hypothalamus, during gestation in Mus musculus and Myotis lucifugus.  Placenta J. 25:712-722.
Li, C. (2005) The ever expanding neuropeptide gene families in the nematode Caenorhabditis elegans.  Parasitology 131:S109-127.
Shan, G., K. Kim, C. Li, and W.W. Walthall (2005) Convergent genetic programs regulate similarities and differences between related motor neuron classes in Caenorhabditis elegans.  Dev. Biol. 280: 494-503.
Novillo, A., S.-J. Won, C. Li, and I.P. Callard (2005) Changes in nuclear receptor and vitellogenin gene expression in response to steroids and heavy metal in Caenorhabditis elegans.  Integr. Comp. Biol. 45:61-71.
Hornsten, A., J. Lieberthal, S. Fadia, R. Malins, L. Ha, X. Xu, I. Daigle, M. Markowitz, G. O’Connor, R. Plasterk, and C. Li. (2007) APL-1, a C. elegans protein related to human Amyloid Precursor Protein, is essential for viability.  Proc. Natl. Acad. Sci. USA 104:1971-1976.  Selected as an Editors’ Choice Science 315:914 (2007)
Liu, T., K. Kim, C. Li, and M. Barr (2007) FMRFamide-like neuropeptides and mechanosensory touch receptor neurons regulate male sexual turning behavior in Caenorhabditis elegans.  J. Neurosci. 27:7174-7182.
Niwa, R., F. Zhou, C. Li, and F. Slack (2008) The expression of the Alzheimer’s amyloid precursor protein-like gene is regulated by developmental timing using microRNAs and their targets I Caenorhabditis elegans. Dev. Biol. 315:418-425.

Seid, M., K. Goode, C. Li, and J. Traniello (2008) Age- and subcaste -related patterns of serotonergic immunoreactivity in the optic lobes of the ant Pheidole dentata. Develop. Neurobiol. 68:1325-1333.

Hoopes, J.T., X. Liu, X. Xu, B. Demeier, E. Folta-Stognlew, C. Li, and Y. Ha (2010) Structural characterization of the E2 domain of APL-1, a C. elegans homolog of human amyloid precursor protein, and its heparin binding site. J. Biol. Chem. 285:2165-2173.

Dimitriadi, M., J.N. Sleigh, A.K. Walker, H.C.-H. Chang, A. Sen, G. Kalloo, J. Harris, T. Barsby, M.B. Walsh, J.S. Satterlee, C. Li, D. Van Vactor, S. Artavanis-Tsakonas, and A. Hart (2010) Conserved genes act as modifiers of invertebrate SMN loss of function defects. PLoS Genetics 6(10): e1001172. doi:10.1371/journal.pgen.1001172.

Arimoto, M., S. Koushika, B. Choudhary, C. Li, K. Matsumoto, and N. Hisamoto (2011) The C. elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein. J. Neurosci. 31:2216-2224.

Cha, D.S., S.E. Hollis, U.S. Datia, S. Lee, J. Ryu, H.R. Jung, E. Kim, K. Kim, M. Lee, C. Li, and M.H. Lee (2012) Differential subcellular localization of DNA topoisomerase-1 isoforms and their roles during Caenorhabditis elegans development.  Gene Expression Patterns 12:189-195.

Ewald, C.Y., D.A. Raps, and C. Li (2012) APL-1, the Alzheimer’s amyloid precursor protein in Caenorhabditis elegans modulates multiple metabolic pathways throughout development.  Genetics 191:493-507.

Ewald, C.Y., R. Chent, L. Tolen, V. Shah, A. Gillani, A. Nasrin, and C. Li (2012) Pan-neuronal expression of APL-1, an APP-related protein, disrupts olfactory, gustatory, and touch plasticity in C. elegans.  J. Neurosci., in press.

Book Chapters & Reviews

Li, C. and K. Kim (2008) Neuropeptides in C. elegans. In WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.142.1, http://www.wormbook.org NIHMSID #125541

Ewald, C.Y. and C. Li (2010) Understanding the molecular basis of Alzheimer’s disease using a Caenorhabditis elegans model system. Brain Structure & Function 214:263-283.
Li, C. and K. Kim (2010) Neuropeptide gene families in Caenorhabditis elegans. In Neuropeptide Systems as Targets for Parasite and Pest Control, Adv. Exp. Med. Biol. 692:98-137.
Ewald, C.Y. and C. Li (2012) Caenorhabditis elegans as a model organism to study APP function.  Exp Brain Res 217:394-411.

 

 

 

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