Professor & Department Head
Molecular and Cellular Neural Development
Our lab is interested in understanding the cellular and molecular mechanisms that drive the formation of the nervous system and how those steps can go awry to cause neural developmental disorders. Specifically, we are investigating the human hereditary sensory and autonomic neuropathy, Familial Dysautonomia. This developmental disorder is marked by devastation of the autonomic nervous system and decreased pain and temperature sensation and results from a mutation in the gene Ikbkap/Elp1, a scaffolding subunit of the Elongator complex. In addition to being a developmental disorder, the disease also causes the degeneration of neurons in the adult central nervous system (CNS) and peripheral nervous system (PNS). Our approach has been to generate mouse models for Familial Dysautonomia in which we delete Ikbkap from different neuronal populations, in order to decipher the underlying pathophysiology that causes the demise of neurons in both the CNS and PNS. With the identification of the cellular and molecular pathways that are active in FD, our goal is to develop therapeutic strategies for thwarting the death of neurons in both the CNS and PNS.
Ueki Y, Shchepetkina V, Lefcort F. 2018. Retina-specific loss of Ikbkap/Elp1 causes mitochondrial dysfunction that leads to selective retinal ganglion cell degeneration in a mouse model of familial dysautonomia.Dis Model Mech. In press
Goffena J, Lefcort F, Zhang Y, Lehrmann E, Chaverra M, Felig J, Walters J, Buksch R, Becker KG, George L. 2018. Elongator and codon bias regulate protein levels in mammalian peripheral neurons.Nat Communication 9(1):889
Lefcort F. 2018. Rethinking the autonomic nervous system: genetics and cell fate. Clin Auton Res. ;28(2):165-166.
Lefcort F, Mergy M, Ohlen SB, Ueki Y, George L. 2017. Animal and cellular models of familial dysautonomia. Clin Auton Res. 27(4):235-243.
Ohlen SB, Russell ML, Brownstein MJ, Lefcort F. 2017. BGP-15 prevents the death of neurons in a mouse model of familial dysautonomia. Proc Natl Acad Sci U S A. 114(19):5035-5040.
Lefcort F, Mergy M, Ohlen SB, Ueki Y, George L. 2017. Animal and cellular models of familial dysautonomia. Clin Auton Res. doi: 10.1007/s10286-017-0438-2.
Chaverra, M. George L, Mergy M, Waller H, Kujawa K, Murnion C, Sharples E, Thorne J, Podgajny N, Grindeland A, Ueki Y, Eiger S, Cusick C, Babcock AM, Carlso GA, Lefcort F. 2017. The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system. Dis Model Mech. 10(5):605-618.
George L., Dunkel, H., Hunnicutt, B.J., Filla, M., Little, C., Lansford, R. and Lefcort. F. 2016. In vivo time-lapse imaging reveals extensive neural crest and endothelial cell interactions during formation of the peripheral nervous system. Developmental Biology. 413(1): 70-85.
Ueki, Y., Ramirez, G., Stabio, M. and Lefcort, F. 2016. Loss of Ikap causes slow, Progressive retinal degeneration in a mouse model of Familial Dysautonomia. eNeuro 3:(5).
Kasemeier-Kulesa, J.C., Morrison, J.A., F. Lefcort, and PM Kulesa. 2015. TrkB/BDNF signaling patterns the sympathetic nervous system. Nature Communication 6:8281-9.
George L, Chaverra M, Wolfe L, Thorne J, Close-Davis M, Eibs A, Riojas V, Grindeland A, Orr M, Carlson GA, Lefcort F. (2013). Familial dysautonomia model reveals Ikbkap deletion causes apoptosis of Pax3+ progenitors and peripheral neurons. PNAS. 110 (46), 18698-18703.
Kasemeier-Kulesa JC, Lefcort F, Kulesa PM. (2013). Dorsal migration and formation of the secondary, permanent chain of sympathetic ganglia as revealed by the confocal time-lapse analysis in chick. Autonomic Neuroscience. 177 (2), 315-315.
Kulesa P, Kasemeier-Kulesa JC, Lefcort F. (2013). Dynamic Formation of the Chick Sympathetic Ganglia. FASEB JOURNAL 27.
Hunnicutt BJ, Chaverra M, George L, Lefcort F. (2012). IKAP/Elp1 is required in vivo for neurogenesis and neuronal survival, but not for neural crest migration. PLoS One. 7(2):e32050.
George, L., J. Kasemeier-Kulesa, B.R. Nelson, and F. Lefcort. (2010). Patterned assembly and neurogenesis in the avian dorsal root ganglion. J. Comp. Neurol. 518(4):405-22. (Cover photo).
Kasemeier-Kulesa, J., P.M. Kulesa, and F. Lefcort (2010). CXCR4 controls ventral migration of sympathetic precursor cells. Journal of Neuroscience. 30(39):13078-88.
Kulesa PM, Lefcort F, Kasemeier-Kulesa JC. (2009). The migration of autonomic precursor cells in the embryo. Auton Neurosci. 151(1):3-9.
George, L., M. Chaverra, V. Todd, R. Lansford and Lefcort, F. (2007). Nociceptive sensory neurons derive from contralaterally migrating, fate restricted neural crest cells. Nature Neuroscience 10 (10): 1287-93.
Kasemeier-Kulesa, J.C., F. Lefcort, and P. M. Kulesa. (2007). Sagittal explant culture for 3D confocal time-lapse analysis of chick peripheral nervous system formation. CSH Protocols. Cold Spring Harbor Labs Press.
Lefcort, F. and George, L. (2007). Neural crest cell fate: to be or not to be prespecified. Cell Adhesion and Migration, 1(4): 199-201.
Hapner, S.J., Chaverra, M., Nielson, K.M., Esper, R., Loeb, J. and Lefcort, F. (2006). NT- 3 and CNTF exert dose-dependent, pleiotropic effects on cells in the immature dorsal root ganglion: Neuregulin-mediated proliferation of progenitor cells and neuronal differentiation. Developmental Biology 297(1):182-97.
Hurley, S., Douglas Clary, Valerie Copie and Lefcort, F. (2006). Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system. Journal of Comparative Neurology 495(2):202-12.
Kasemeier-Kulesa, J.C., Bradley, R., Pasquale, E., Lefcort, F. and Kulesa, P.M.(2006). Eph/ephrins and N-cadherin coordinate to control the pattern of sympathetic ganglia. Development. 133(24):4839-47.
Lefcort, Frances, Timothy O'Connor and Paul Kulesa. (2006). A comparative analysis of neural crest cell and axonal growth cone dynamics and behavior. In press in Intracellular Mechanisms in Neuritogenesis Editor, Ivan DeCurtis, Springer-Verlag.
Kasemeier-Kulesa, J.C., Paul M. Kulesa, and Lefcort, F. (2005). Imaging neural crest cell Dynamics during formation of dorsal root ganglia and sympathetic ganglia. Development, 132: pg. 235-245.
Kasemeier, J.C., F. Lefcort, S.E. Fraser and P. Kulesa. (2004). A novel sagittal slice explant technique for time-lapse imaging of the formation of the chick peripheral nervous system. Symposia; In Imaging in neuroscience and development (ed. R.Yuste and A. Konnerth). Cold Spring Harbor, NY. Cold Spring Harbor Press.
Nelson, B.R., K.Claes, M.Chaverra, V. Todd and Lefcort, F. (2004). NELL2 promotes Motor and sensory neuron differentiation and stimulates mitogenesis in DRG in vivo. Developmental Biology, 270: 322-335.
Nielson, K. ,Chaverra, M., Zigmond, R. and Lefcort, F. (2004). PACAP induces differentiation of DRG neurons: abrogation by NT-3 and CNTF. Molecular and Cellular Neuroscience, 25: 629-641.
Nelson, B.R. M. Sadhu, J. C. Kasemeier, L. W. Anderson, and F. Lefcort (2004). Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia. 29(3):618-29. Developmental Dynamics.
BIOL 510: Topics In Neurobiology
WWAMI Medical Education Program:
MEDS 532: Nervous System
B.A. in Biology, Smith College, Northampton, Massachusetts, l982, cum laude.
Ph.D in Neurobiology, University of California, Berkeley, l988 (Dr. David R. Bentley, mentor).
Postdoctoral Fellow and Associate, University of California, San Francisco Howard Hughes Medical Institute and Department of Physiology, 10/88-8/94 (Dr. Louis F. Reichardt, mentor).