Courtney Miller, PhD

Associate Professor
Department of Molecular Medicine
Florida Campus



Scripps Research Joint Appointments

Faculty, Pearson Center for Alcohol and Addiction Research
Associate Professor, Department of Neuroscience
Faculty, Graduate Program

Other Joint Appointments

Affiliate Research Professor, Dept. of Biological Sciences, Florida Atlantic University

Research Focus

The Miller Lab is working to develop new medications for the treatment of disorders marked by persistent, unwanted memories – specifically substance use disorder (SUD; addiction) and posttraumatic stress disorder (PTSD). Mechanistically, our efforts are large focused on epigenetic and synaptic structural players.

DEVELOPMENT OF THERAPEUTICS TO PREVENT ADDICTION RELAPSE

Dr. Miller has long been interested in ways to selectively disrupt drug-associated memories (Reconsolidation; Miller and Marshall, Neuron, 2005) and the mechanisms that contribute to the persistence of memory (DNA methylation; Miller et al, Nature Neuroscience, 2010). In bringing these two areas together, the Miller Lab made the surprising discovery that memories associated with the commonly abused stimulant, methamphetamine, employ a unique, actin-based storage mechanism in the brain’s emotional memory center, the amygdala, that allows for their selective disruption (Young et al, Biological Psychiatry, 2014). This was followed by identification of nonmuscle myosin II (NMII) as a viable therapeutic target (Young et al, Molecular Psychiatry, 2015) and we are now in the middle of a drug development program supported by the NIH’s Blueprint Neurotherapeutics Network to develop a clinically safe NMII inhibitor. The goal is to enter a Phase 1a safety trial in 2020.

MicroRNA REGULATION OF TRAUMATIC MEMORY RELATED TO PTSD

We recently developed an animal model with PTSD-like features, including differential susceptibility, which has been replicated by other groups. The stress susceptible subgroup displays persistent, stress-enhanced fear memory, hyperarousal, amygdala hyperactivation and differential expression of genes with known polymorphisms in human PTSD genomic studies (Sillivan et al, Biological Psychiatry, 2017). Importantly, the stress susceptible population can be identified by training behavior, removing the need for additional phenotyping that introduces a molecular confound. Because the model was developed in an inbred mouse line (c57’s), it’s an excellent opportunity to investigate epigenetic mechanisms. To date we have largely focused on noncoding RNAs, including miRNAs. Small RNA-sequencing integrated with quantitative proteomics revealed a panel of miRNAs persistently upregulated in the amygdala of stress susceptible mice. We recently completed a study demonstrating a functional role for one of these miRNAs, which is also expressed in the human amygdala. Working with our collaborators, we also discovered the miRNA’s passenger strand is elevated in serum of a Dutch military cohort diagnosed with PTSD six months after a combat deployment to Afghanistan, indicating this miRNA may be a therapeutic target and biomarker for PTSD (Sillivan et al, Biorxiv).


Education

Ph.D. (Neurobiology & Behavior), University of California, Irvine, Center for the Neurobiology of Learning & Memory, 2005
B.S. (Biopsychology), University of California, Santa Barbara, 1999

Professional Experience

Program in Technology Ventures, UAB Collat School of Business
2009-2013 Assistant Professor, Metabolism and Aging, Scripps Research

Awards & Professional Activities

Host, SFN Women in Neuroscience Luncheon, "Effective self-promotion" (2018)
Invited Participant, NIH Opioid Meeting Series, "Understanding the neurobiological mechanisms of pain" (2017)
Organizer, SFN Professional Development Workshop, "Addressing issues facing women in the early stages of their scientific career"
Presidential Early Career Award for Scientists and Engineers (PECASE), awarded by President Obama (2016)
Distinguished Speaker Award, UNC Department of Psychology and Neuroscience (2016)
Most influential paper published by Neuron in 2007 (2014)
Associate Member, American College of Neuropharmacology (ACNP; 2014)
Faculty of 1000 Selections (2013, 2010, 2007)
Consultant, Scientific and market expertise, DisvoeryBioMed and EnVivo Pharmaceuticals (2008-2009)
Kauffman Fellow - Program for Venture Education (2008)
Co-Organizer, SFN Social, Professional Women's Nexus (PWN), "Breaking barriers for young women in science" (2008-present)
Co-Founder, Professional Women's Nexus (PWN) (2007)
NIDA Young Investigator Award (2005) 


Selected References

All Publications

Griggs EM, Young EJ, Rumbaugh G, Miller CA. (2013) MicroRNA-182 regulates amygdala-dependent memory formation. Journal of Neuroscience. 2013 Jan 23;33(4):1734-40.

Clement JP, Aceti M, Creson TK, Ozkan ED, Shi Y, Reish NJ, Almonte AG, Miller BH, Wiltgen BJ, Miller CA, Xu X, Rumbaugh G. (2012) Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses. Cell 2012 Nov 9;151(4):709-23.

Gavin CF, Rubio MD, Young E, Miller C, Rumbaugh G. (2011) Myosin II motor activity in the lateral amygdala is required for fear memory consolidation. Learning & Memory. 2011 Dec 14;19(1):9-14. Print 2012 Jan.

Mikaelsson MA, Miller CA. (2011) DNA methylation: a transcriptional mechanism co-opted by the developed mammalian brain? Epigenetics. 2011 May;6(5):548-51. Epub 2011 May 1.

Mikaelsson MA, Miller CA. (2011) The path to epigenetic treatment of memory disorders. Neurobiolgy of Learning and Memory. 2011 Jul;96(1):13-8. Epub 2011 Feb 12. Review.

Rubio MD, Johnson R, Miller CA, Huganir RL, Rumbaugh G. (2011) Regulation of synapse structure and function by distinct myosin II motors. The Journal of Neuroscience. 2011 Jan 26;31(4):1448-60.

Rex C, Gavin CF, Rubio MD, Kramar EA, Jia Y, Huganir RL, Muzyczka N, Gall CM, Miller CA, Lynch G and Rumbaugh G (2010) Myosin IIB regulates actin dynamics during synaptic plasticity and memory formation. Neuron 67:603-17.

Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A, Yancey CR, Rivera IM, Rubio MD, Rumbaugh G and Sweatt JD (2010) Cortical DNA methylation maintains remote memory. Nature Neuroscience 13: 664-6.

Kilgore M*, Miller CA*, Fass DM, Hennig KM, Haggerty S, Sweatt JD and Rumbaugh G (2010) Inhibitors of Class I histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s Disease. Neuropsychopharmacology 35: 870-80.

Cahill ME, Xie Z, Day M, Barbolina MV, Miller CA, Weiss C, Radulovic J, Sweatt JD, Disterhoft JF, Surmeier DJ and Penzes P. (2009) Kalarin regulates cortical spine morphogenesis and disease-related behavioral phenotypes. Proceedings of the National Academy of Sciences 106: 13058-63.

Guo X, Hamilton PJ, Reish N, Sweatt JD, Miller CA, and Rumbaugh G (2008) Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of schizophrenia. Neuropsychopharmacology 34: 1659-72.

Miller CA, Campbell SL and Sweatt JD (2008) DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiology of Learning and Memory 89: 599-603.

Miller CA and Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53: 857-69.

Levenson MJ, Roth TL, Lubin FD, Miller CA, Huang IC, Desai P, Malone L, Sweatt JD (2006) Evidence that DNA (Cytosine-5) methyltransferases regulate synaptic plasticity in the hippocampus. Journal of Biological Chemistry 281: 15763-73.

Miller CA and Marshall JF (2005) Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory. Neuron 47: 873-84.

Miller CA and Marshall JF (2005). Altered Fos expression in neural pathways involved in cue-elicited drug seeking. European Journal of Neuroscience 21, 1385-93.

Miller CA and Marshall JF (2004). Altered prelimbic cortex output during cue-elicited drug seeking. Journal of Neuroscience 24, 6889-97.



Clement JP, Ozkan ED, Aceti M, Miller CA and Rumbaugh G (2013) SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity. Journal of Neuroscience 33:10447-52. 

Young EJ, Griggs EM, Aceti M, Fuchs RA, Zigmond Z, Rumbaugh G and Miller CA (2014) Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization. Biological Psychiatry 75:96-104. (Priority Communication)        

Ozkan E, Creson TC, Kramar EA, Rojas C, Seese RR, Babyan AH, Shi Y, Lucero R, Xu X, Noebels JL, Miller CA, Lynch G and Rumbaugh G (2014) Reduced cognition in Syngap1 mutants is caused by isolated damage within developing forebrain excitatory neurons. Neuron 82:1317-33. 

Aguilar-Valles A, Vaissiere T, Griggs EM, Mikaelsson M, Takacs I, Young EJ, Rumbaugh G and Miller CA (2014) Methamphetamine-associated memory is regulated by a writer and an eraser of permissive histone methylation. Biological Psychiatry 76:57-65. 

Aceti M, Creson TK, Vaissiere T, Rojas C, Huang W, Wang Y, Petralia RS, Page DT, Miller CA and Rumbaugh G (2015) Syngap1 haploinsufficiency damages a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly. Biological Psychiatry 77:805-15. 

Rumbaugh G*, Sillivan SE*, Ozkan ED, Rojas CS, Hubbs CR, Aceti M, Kilgore M, Kudugunti S, Puthanveettil SV, Sweatt JD, Rusche J and Miller CA (2015) Pharmacological selectivity within class I histone deacetylases predicts effects on synaptic function and memory rescue. Neuropsychopharmacology 40:2307-16.

Sillivan SE, Vaissiere T and Miller CA (2015) Neuroepigenetic regulation of pathogenic memories. Neuroepigenetics, 1:28-33.

Ozkan ED, Aceti M, Creson TK, Rojas CS, Hubbs CR, McGuire MN, Kakad PP, Miller CA and Rumbaugh G (2015) Input-specific regulation of hippocampal circuit maturation by non-muscle myosin IIB. Journal of Neurochemistry 134:429-44. 

Mediouni S,  Miller C, Marcondes MCG, McLaughlin J, Valente ST (2015) The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders. Frontiers in Microbiology, 6:1164. 

Young EJ, Briggs SB and Miller CA (2015) The actin cytoskeleton as a therapeutic target for the prevention of relapse to methamphetamine use. CNS & Neurological Disorders - Drug Targets 14:731-7. 

Young EJ*, Blouin AM*, Briggs SB*, Sillivan SE, Lin L, Cameron MD, Rumbaugh G and Miller CA (2016) Nonmuscle myosin IIB as a therapeutic target for the prevention of relapse to methamphetamine use. Molecular Psychiatry, 21:615-23. 

Mavrikavi M, Girardet C, Kern A, Brantley AF, Miller CA, Macarthu Hr, Marks DL and Butler AA (2016) Melantocortin-3 receptors in the limbic system mediate feeding-related motivational responses during weight loss. Molecular Metabolism, 5:566-79. 

Blouin AM*, Sillivan SE*, Joseph NF and Miller CA (2016) The potential of epigenetics in stress-enhanced fear learning models of PTSD. Learning & Memory, 23:576-86. 

Girardet C, Mavrikaki MM, Stevens JR, Miller CA, Marks DL and Butler AA (2017) Melanocortin-3 receptors expressed in Nkx2.1(+ve) neurons are sufficient for controlling appetitive responses to hypocaloric conditioning. Scientific Reports, 7:44444. 

Briggs SB*, Blouin AM*, Young EJ, Rumbaugh G and Miller CA (2017) Memory disrupting effects of nonmuscle myosin II inhibition depend on the class of abused drug and brain region. Learning & Memory, 24:70-75.

Young EJ, Briggs SB, Rumbaugh G and Miller CA (2017) Nonmuscle myosin II inhibition disrupts methamphetamine-associated memory in females and adolescents. Neurobiology of Learning and Memory, 139: 109-116. 

Sillivan SE, Joseph NF, Jamieson S, King ML, Chevere-Torres I, Fuentes I, Shumyatsky GP, Brantley AF, Rumbaugh G and Miller CA (2017) Susceptibility and resilience to PTSD-like behaviors in inbred mice. Biological Psychiatry, 82:924-933. 

Furth D, Vaissiere T, Tzortzi O, Xuan Y, Martin A, Lazaridis I, Spigolon G, Fisone G, Tomer R, Deisseroth K, Carlen M, Miller CA, Rumbaugh G and Meletis K. An interactive framework for whole-brain maps at cellular resolution. Nature Neuroscience, 21:139-149. 

Spicer TP, Hubbs C, Vaissiere T, Collia D, Rojas C, Kilinc M, Vick K, Madoux F, Baillargeon P, Shumate J, Martemyanov KA, Page DT, Puthanveettil S, Hodder P, Davis R, Miller CA, Scampavia L, Rumbaugh G (2018) Improved scalability of neuron-based phenotypic screening assays for therapeutic discovery in neuropsychiatric disorders. Molecular Neuropsychiatry, 3:141-150.

Briggs SB, Hafenbreidel M, Young EJ, Rumbaugh G and Miller CA (2018) The role of nonmuscle myosin II in polydrug memories and memory reconsolidation. Learning & Memory, (in press).

Blouin AM, Pisupati S, Hoffer CG, Hafenbreidel M, Jamieson SE, Rumbaugh G and Miller CA. Social stress-potentiated methamphetamine seeking. Addiction Biology, (in press).

Sillivan SE, Jamieson S, de Nijs L, Jones ME, Snijders C, Klengel T, Joseph NF, Krauskopf J, Kleinjans J, Vinkers CH, Boks MPM, Geuze E, Vermetten E, Ressler KJ, Rutten BPF, Rumbaugh G and Miller CA. microRNA regulation of persistent stress-enhanced memory. Biorxiv, doi.org/10.1101/379594.


Links

VIDEO: Can a drug erase selective memories to help addicts?

Scientists may have found a way to make you forget that you’re addicted to meth (Washington Post)

Scripps Florida’s Courtney Miller Wins Presidential Early Career Award

Scripps awarded grant to develop drug that could erase meth-induced memories (Sun Sentinel)

Michael Oldstone, Courtney Miller Named 2015 TSRI Outstanding Mentors

Memories of Meth Can Be Deleted (Scientific American)

Learning and memory: Dynamic DNA methylation (Nature Neuroscience Reviews)

Memories may be stored on your DNA (New Scientist)

Abolishing Addiction (The Economist)

The Ten most Revelatory Discoveries of the Year: Chemicals can cure addiction (Seed Magazine)