Jeanne Paz’s lab aims to improve the outcome for patients with epilepsy by studying the disorder in animal models and identifying potential targets for new therapeutic interventions. A signature approach in her lab is optogenetics, which allows her team to disrupt the function of specific brain cells in live animals. Using this approach, the group identified a small brain region called the thalamus as a choke point for various forms of epilepsy—and a promising target for future therapies. Current research includes understanding how the thalamus controls seizures in distant brain regions, and how brain lesions like stroke and trauma can lead to epilepsy.
Areas of Expertise
Paz’s team showed they could stop epileptic seizures in mice in real time and with no side effects using optogenetics to control specific brain cells known as thalamocortical neurons. This work identified thalamocortical neurons as potential targets in the development of effective therapies against post-stroke seizures.
Optogenetics could also be used to identify the cells and circuits responsible for other forms of epilepsy or for neurological and cognitive disorders, leading to targeted therapeutics against these diseases as well.
Recent work by the team shows a link between chronic brain inflammation and the development of post-injury epilepsy, suggesting that certain anti-inflammatory drugs could be used in the treatment of this form of epilepsy.
Associate Investigator, Gladstone Institutes
Associate Professor of Neurology, UC San Francisco
Jeanne Paz is an associate investigator at Gladstone Institutes. She is also an associate professor of neurology in the Kavli Institute for Fundamental Neuroscience at UC San Francisco.
Before joining Gladstone, Paz completed a postdoctoral fellowship at Stanford University, where she identified seizure control points in the brain. Paz earned her undergraduate and graduate degrees from Université Pierre et Marie Curie in Paris. As a graduate student, she studied the role of basal ganglia in regulating absence epilepsy and received an award for the best neuroscience PhD thesis in France.
How Did You Get Your Start in Science?
“I always wondered: if we knew how the brain works, would we be able to understand ourselves?”
Honors and Awards
2019 Vilcek Prize for Creative Promise, Vilcek Foundation
2019 Associate Editor, Progress in Neurobiology
2017 Top reviewer 2 years in a row, Nature Publishing Group
2015 Michael Prize (Best Epilepsy Research), International League Against Epilepsy
2013 Challenge Award, Citizens United for Research in Epilepsy
2012 K99 Pathway to Independence Career Award, National Institutes of Health
2009 American Epilepsy Foundation Fellowship
2008 Best PhD in Neuroscience award in France (Prix de Thèse), French Society for Neuroscience
2007 Linus Pauling Graduate, University Pierre and Marie Curie
2005 Award for the best poster presentation in Neuroscience, 7ème Colloque de la Société des Neurosciences Française, French Society for Neuroscience
2003 Graduate Research Fellowship, French Ministry of Research and Technology
2002 Merit Scholarship, French Science Foundation, University Pierre and Marie Curie
- Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury. Holden SS, Grandi FC, Aboubakr O, Higashikubo B, Cho FS, Chang AH, Forero AO, Morningstar AR, Mathur V, Kuhn LJ, Suri P, Sankaranarayanan S, Andrews-Zwilling Y, Tenner AJ, Luthi A, Aronica E, Corces MR, Yednock T, Paz JT. Science. 2021 09 10; 373(6560):eabj2685.
- Gamma rhythms and visual information in mouse V1 specifically modulated by somatostatin+ neurons in reticular thalamus. Hoseini MS, Higashikubo B, Cho FS, Chang AH, Clemente-Perez A, Lew I, Ciesielska A, Stryker MP, Paz JT. Elife. 2021 04 12; 10.
- Behavioral and neural network abnormalities in human APP transgenic mice resemble those of App knock-in mice and are modulated by familial Alzheimer's disease mutations but not by inhibition of BACE1. Johnson ECB, Ho K, Yu GQ, Das M, Sanchez PE, Djukic B, Lopez I, Yu X, Gill M, Zhang W, Paz JT, Palop JJ, Mucke L. Mol Neurodegener. 2020 09 14; 15(1):53.
- Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation. Pai EL, Chen J, Fazel Darbandi S, Cho FS, Chen J, Lindtner S, Chu JS, Paz JT, Vogt D, Paredes MF, Rubenstein JL. Elife. 2020 05 26; 9.
- Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function. Pai EL, Vogt D, Clemente-Perez A, McKinsey GL, Cho FS, Hu JS, Wimer M, Paul A, Fazel Darbandi S, Pla R, Nowakowski TJ, Goodrich LV, Paz JT, Rubenstein JLR. Cell Rep. 2019 01 29; 26(5):1157-1173.e5.
- Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome. Ritter-Makinson S, Clemente-Perez A, Higashikubo B, Cho FS, Holden SS, Bennett E, Chkhaidze A, Eelkman Rooda OHJ, Cornet MC, Hoebeek FE, Yamakawa K, Cilio MR, Delord B, Paz JT. Cell Rep. 2019 Jan 22; 26(4):1071.
- Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome. Ritter-Makinson S, Clemente-Perez A, Higashikubo B, Cho FS, Holden SS, Bennett E, Chkhaidze A, Eelkman Rooda OHJ, Cornet MC, Hoebeek FE, Yamakawa K, Cilio MR, Delord B, Paz JT. Cell Rep. 2019 01 02; 26(1):54-64.e6.
- Conditional Bistability, a Generic Cellular Mnemonic Mechanism for Robust and Flexible Working Memory Computations. Rodriguez G, Sarazin M, Clemente A, Holden S, Paz JT, Delord B. J Neurosci. 2018 05 30; 38(22):5209-5219.
- Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development. Vainchtein ID, Chin G, Cho FS, Kelley KW, Miller JG, Chien EC, Liddelow SA, Nguyen PT, Nakao-Inoue H, Dorman LC, Akil O, Joshita S, Barres BA, Paz JT, Molofsky AB, Molofsky AV. Science. 2018 03 16; 359(6381):1269-1273.
- Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms. Clemente-Perez A, Makinson SR, Higashikubo B, Brovarney S, Cho FS, Urry A, Holden SS, Wimer M, Dávid C, Fenno LE, Acsády L, Deisseroth K, Paz JT. Cell Rep. 2017 06 06; 19(10):2130-2142.
- Absence seizure susceptibility correlates with pre-ictal ß oscillations. Sorokin JM, Paz JT, Huguenard JR. J Physiol Paris. 2016 11; 110(4 Pt A):372-381.
- Bidirectional Control of Generalized Epilepsy Networks via Rapid Real-Time Switching of Firing Mode. Sorokin JM, Davidson TJ, Frechette E, Abramian AM, Deisseroth K, Huguenard JR, Paz JT. Neuron. 2017 Jan 04; 93(1):194-210.
- Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. Lui H, Zhang J, Makinson SR, Cahill MK, Kelley KW, Huang HY, Shang Y, Oldham MC, Martens LH, Gao F, Coppola G, Sloan SA, Hsieh CL, Kim CC, Bigio EH, Weintraub S, Mesulam MM, Rademakers R, Mackenzie IR, Seeley WW, Karydas A, Miller BL, Borroni B, Ghidoni R, Farese RV, Paz JT, Barres BA, Huang EJ. Cell. 2016 May 05; 165(4):921-35.
- Voices of biotech. Amit I, Baker D, Barker R, Berger B, Bertozzi C, Bhatia S, Biffi A, Demichelis F, Doudna J, Dowdy SF, Endy D, Helmstaedter M, Junca H, June C, Kamb S, Khvorova A, Kim DH, Kim JS, Krishnan Y, Lakadamyali M, Lappalainen T, Lewin S, Liao J, Loman N, Lundberg E, Lynd L, Martin C, Mellman I, Miyawaki A, Mummery C, Nelson K, Paz J, Peralta-Yahya P, Picotti P, Polyak K, Prather K, Qin J, Quake S, Regev A, Rogers JA, Shetty R, Sommer M, Stevens M, Stolovitzky G, Takahashi M, Tang F, Teichmann S, Torres-Padilla ME, Tripathi L, Vemula P, Verdine G, Vollmer F, Wang J, Ying JY, Zhang F, Zhang T. Nat Biotechnol. 2016 Mar; 34(3):270-5.
- Microcircuits and their interactions in epilepsy: is the focus out of focus? Paz JT, Huguenard JR. Nat Neurosci. 2015 Mar; 18(3):351-9.
- Optogenetics and epilepsy: past, present and future. Paz JT, Huguenard JR. Epilepsy Curr. 2015 Jan-Feb; 15(1):34-8.
- Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury. Paz JT, Davidson TJ, Frechette ES, Delord B, Parada I, Peng K, Deisseroth K, Huguenard JR. Nat Neurosci. 2013 Jan; 16(1):64-70.
- R U OK? The Novel Therapeutic Potential of R Channels in Epilepsy. Paz JT, Huguenard JR. Epilepsy Curr. 2012 Mar; 12(2):75-6.
- A theory of rate coding control by intrinsic plasticity effects. Naudé J, Paz JT, Berry H, Delord B. PLoS Comput Biol. 2012 Jan; 8(1):e1002349.
- A new mode of corticothalamic transmission revealed in the Gria4(-/-) model of absence epilepsy. Paz JT, Bryant AS, Peng K, Fenno L, Yizhar O, Frankel WN, Deisseroth K, Huguenard JR. Nat Neurosci. 2011 Aug 21; 14(9):1167-73.
- Neocortical excitation/inhibition balance in information processing and social dysfunction. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K. Nature. 2011 Jul 27; 477(7363):171-8.
- Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus. Paz JT, Christian CA, Parada I, Prince DA, Huguenard JR. J Neurosci. 2010 Apr 14; 30(15):5465-79.
- Multiple forms of activity-dependent intrinsic plasticity in layer V cortical neurones in vivo. Paz JT, Mahon S, Tiret P, Genet S, Delord B, Charpier S. J Physiol. 2009 Jul 01; 587(Pt 13):3189-205.
- Activity of ventral medial thalamic neurons during absence seizures and modulation of cortical paroxysms by the nigrothalamic pathway. Paz JT, Chavez M, Saillet S, Deniau JM, Charpier S. J Neurosci. 2007 Jan 24; 27(4):929-41.
- Rhythmic bursting in the cortico-subthalamo-pallidal network during spontaneous genetically determined spike and wave discharges. Paz JT, Deniau JM, Charpier S. J Neurosci. 2005 Feb 23; 25(8):2092-101.
- On the activity of the corticostriatal networks during spike-and-wave discharges in a genetic model of absence epilepsy. Slaght SJ, Paz T, Chavez M, Deniau JM, Mahon S, Charpier S. J Neurosci. 2004 Jul 28; 24(30):6816-25.
- Distal His----Arg mutation in bovine myoglobin results in a ligand binding site similar to the abnormal beta site of hemoglobin Zurich (beta 63 His----Arg). Shimada H, Dong A, Matsushima-Hibiya Y, Ishimura Y, Caughey WS. Biochem Biophys Res Commun. 1989 Jan 16; 158(1):110-4.