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Neuroscience PhD at Wake Forest University at Wake Forest University

Wake Forest University Graduate School » Neuroscience PhD at Wake Forest University

Carol Milligan

Carol Milligan

Professor, Neurobiology & Anatomy Translational Science Institute
Office of Women in Medicine and Science
Translational Science Institute

Studies of the events of central nervous system (CNS) development contribute not only to our understanding of developmental processes, but also lay foundations for understanding pathological conditions. Many individual factors are known to play key roles in CNS development, including extracellular matrix molecules, trophic factors, cytokines and individual cellular populations.

The interaction of such factors and cells mediate developmental events to prompt precise development of a functional, mature CNS, and while pathological events are not necessarily identical to those in development, understanding regulation and function in a "defined" physiological developmental situation will provide an understanding of possible regulation and function in pathology.

The research focus of my laboratory is to understand the underlying cellular and molecular mechanisms that mediate neuronal death and survival, critical events during CNS development and in pathological conditions such as spinal cord injury and neurodegenerative disorders. By using a well defined developmental model of avian spinal motoneuron death, we have begun to identify some of the "players" of neuronal cell death during CNS development.

These molecules and events also appear to have substantial roles in neurodegenerative disorders, and we believe that by developing ways to modulate these we may be able to provide protection for injured cells that would normally die and allow them to recover.


Oppenheim RW, Milligan CE, von Bartheld CS. Programmed cell death and neurotrophic factors In: Squire LR, Berg D, Bloom FE, Du Lac S, Ghosh A, Spitzer NC, eds. Fundamental neuroscience. 4th ed. Boston: Elsevier/Academic Press;2013: 405-435.


Taylor AR, Gifondorwa DJ, Robinson MB, Strupe JL, Prevette D, Johnson JE, Hempstead B, Oppenheim RW, Milligan CE. Motoneuron programmed cell death in response to proBDNF. Dev Neurobiol. 2012;72(5):699-712.


Gifondorwa DJ, Jimenz-Moreno R, Hayes CD, Rouhani H, Robinson MB, Strupe JL, Caress J, Milligan C. Administration of recombinant heat shock protein 70 delays peripheral muscle denervation in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Neurol Res Int. 2012;2012():170426.


Hicks AN, Lorenzetti D, Gilley J, Lu B, Andersson KE, Miligan C, Overbeek PA, Oppenheim R, Bishop CE. Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) regulates axon integrity in the mouse embryo. PLoS One. 2012;7(10):e47869.


Sherman A, Bowser R, Grasso D, Power B, Milligan C, Jaffa M, Cudkowicz M.Proposed BioRepository platform solution for the ALS research community. Amyotroph Lateral Scler. 2011;12(1):11-16.


Robinson MB, Gifondorwa DJ, Milligan C. Mechanisms of the motoneuron stress response and its relevance in neurodegeneration In: McNeill AS, ed. Neurodegeneration: theory, disorders, and treatments. New York: Nova Biomedical;2011: 45-62.


Milligan C, Gifondorwa D. Isolation and culture of postnatal spinal motoneurons. Methods Mol Biol. 2011;793(Pt 2):77-85.


Oppenheim RW, Milligan C, Sun W. Programmed cell death during nervous system development: mechanisms, regulation, functions, and implications for neurobehavioral ontogeny In: Blumberg MS, Freeman JH, Robinson SR, eds. Oxford handbook of developmental behavioral neuroscience. New York: Oxford University Press;2010: 76-107.


Markert CD, Kim E, Gifondorwa DJ, Childers MK, Milligan CE. A single-dose resveratrol treatment in a mouse model of amyotrophic lateral sclerosis. J Med Food. 2010;13(5):1081-1085.


Oppenheim R, Milligan C. Early changes in ALS: where does the end begin? [abstract]. J Physiol Sci. 2010;60(Suppl 1):S22.


Hernandez S, Texido L, Caldero J, Ciutat D, Piedrafita L, Casanovas A, Caress J, Prevette D, Oppenheim RW, Milligan C, et al. Increased intramuscular nerve branching and inhibition of programmed cell death of chick embryo motoneurons by immunoglobulins from patients with motoneuron disease. J Neuroimmunol. 2010;229(1-2):157-168.


Oppenheim R, Milligan C.Programmed cell death


Yoshikawa M, Vinsant S, Mansfield CM, Gifondorwa DJ, Pace L, Messi LM [sic] [Messi ML], Caress J, Cartwright M, Delbono O, Oppenheim RW, Milligan CE, et al.Identification of changes in muscle, neuromuscular junctions and spinal cord at early pre-symptomatic stages in the mutant SOD1 mouse model of ALS may provide novel insight for diagnosis and treatment development [abstract]. Soc Neurosci Abstr. 2009;2009(Neuroscience Meeting Planner):.


Hayes CD, Milligan CE. Motorneuron maintenance in the absence of the JNK1 or JNK2 isoforms [abstract]. Soc Neurosci Abstr. 2009;2009(Neuroscience Meeting Planner):.


Robinson MB, Taylor AR, Gifondorwa DJ, Tytell M, Milligan CE. Exogenous Hsc70, but not thermal preconditioning, confers protection to motoneurons subjected to oxidative stress. Dev Neurobiol. 2008;68(1):1-17.


Tytell M, Robinson MB, Milligan CE. Release of heat shock proteins and their effects when in the extracellular space in the nervous system In: Asea AAA, Brown IR, eds. Heat shock proteins and the brain: implications for neurodegenerative diseases and neuroprotection. Dordrecht (Netherlands): Springer;2008: 257-272.


Macosko JC, Newbern JM, Rockford J, Chisena EN, Brown CM, Holzwarth GM, Milligan CE. Fewer active motors per vesicle may explain slowed vesicle transport in chick motoneurons after three days in vitro. Brain Res. 2008;1211():6-12.


Taylor AR, Gifondorwa DJ, Newbern JM, Robinson MB, Strupe JL, Prevette D, Oppenheim RW, Milligan CE. Astrocyte and muscle-derived secreted factors differentially regulate motoneuron survival. J Neurosci. 2007;27(3):634-644.



Newbern J, Taylor A, Robinson M, Lively MO, Milligan CE. c-Jun N-terminal kinase signaling regulates events associated with both health and degeneration in motoneurons. Neuroscience. 2007;147(3):680-692.


Taylor AR, Robinson MB, Gifondorwa DJ, Tytell M, Milligan CE. Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Dev Neurobiol. 2007;67(13):1815-1829.


Gifondorwa DJ, Robinson MB, Hayes CD, Taylor AR, Prevette DM, Oppenheim RW, Caress J, Milligan CE. Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis. J Neurosci. 2007;27(48):13173-80.


Hayes CD, Gifondorwa DJ, Herdegen TM, Milligan CE. Absence of individual JNK isoforms results in altered spinal motoneuron programmed cell death [abstract]. Soc Neurosci Abstr. 2007;2007(Abstr Viewer):.


The overall focus of the research in Dr. Milligan’s lab is to understand the intra- and intercellular mechanisms that mediate motor neuron survival and death during normal development and in ALS and other motor neuron diseases.