COMBINEDBrain coordinates collaborative research programs designed to accelerate therapeutic development for rare neurological disorders. By bringing together patient advocacy organizations, clinicians, and researchers, the consortium supports initiatives that advance diagnosis, scientific discovery, therapeutic development, and clinical trial readiness across many rare disease communities.
These programs span the therapeutic development pathway—from early identification of genetic disorders to the studies needed to prepare diseases for clinical trials and regulatory engagement.
The COMBINEDBrain Translational Research Pipeline
COMBINEDBrain supports research and infrastructure across the therapeutic development pathway. Through coordinated programs and partnerships, the consortium helps rare disease communities generate the scientific knowledge, clinical data, and collaborative networks needed to move potential therapies from discovery toward clinical trials and eventual approval.
Selected Publications from the COMBINEDBrain Team |
2026
Bryan, B. A., V. Faria, K. Esposito, D. Boyce, S. Poliquin, I. Terry, M. Wright, A. Abuhl, A. Rosenberg, D. Bearden, J. West, and S. Drislane. 2026. 'Caregiver perspectives on disease burden and treatment priorities in KCNT1-related disorders', Epilepsy Behav, 181: 111053.
Gelber,
A., H. Romero, D. Burrows, D. S. Whittaker, D. Carlin, E. A. Mukamel,
and P. Desplats. 2026. 'Spatial transcriptomics reveals brain-wide
circadian disruption in an Alzheimer's disease model', bioRxiv.
Zigler,
C. K., M. McFatrich, N. Lucas, K. Plyler, L. Zapata-Leiva, K. Gordon,
H. N. Jones, L. Lin, J. Kern, A. Radar, D. Chen, E. Bergelson, K. Still,
B. Hinger, C. G. Delagrammatikas, S. Poliquin, B. P. Short, L.
Marfia-Ash, K. Stephens, H. O. Oyler, J. M. Graglia, K. Worth, C. Son
Rigby, J. R. Goss, B. Bigelow, G. Bliss, K. Beatty, L. Schust Myers, M.
Thelen, N. Summerfield, T. J. Bichell, and B. B. Reeve. 2026. 'The
spectrum of communication abilities in children with 12 rare
neurodevelopmental disorders: a qualitative study with caregivers', J Child Psychol Psychiatry, 67: 740-54.
2025
Connors, K. L., N. E. Carmichael, T. J. Bichell, K. A. Dies, and Z. J. Frazier. 2025. 'Development of a Patient and Caregiver-Centered Pediatric Disease Concept Model for Kleefstra Syndrome', Sage Open Pediatr, 12: 30502225251336880.
Gomes, A. T., A. Moore, M. Cross, C. Hardesty, K. David, M. G. Sampedro, S. Dube, S. Weil-Chalker, A. G. Montepagano, U. Christel, R. Martin, A. Wheeler, W. H. Tan, L. M. Bird, and T. J. Bichell. 2025. 'Community-Sourced Reporting of Mortalities in Angelman Syndrome (1979-2022)', Am J Med Genet A, 197: e63961.
Weston,
K. P., A. M. Gunelson, S. E. Maloney, X. Ge, J. A. Stelzer, K. S. Kim,
S. Collier, M. M. Mindt, M. J. Agajanian, M. B. Major, D. Goldfarb, K.
K. Noguchi, and J. J. Yi. 2025. 'The gain-of-function UBE3A(Q588E)
variant causes Angelman-like neurodevelopmental phenotypes in mice', Sci Rep, 15: 9152.
2024
Heilmann, R., A. Pfalzer, T. J. Bichell, A. Terala, A. Campbell, D. Taatjes, J. Ghoumid, C. Grueter, J. Bain, R. Strich, V. Dias, K. Sokorai, N. Seaver, K. Sexton, and K. Boychuck. 2024. 'The MED13L Foundation strategic research plan: a roadmap to the future', Ther Adv Rare Dis, 5: 26330040241290252.
Poliquin,
S., G. Nwosu, K. Randhave, W. Shen, C. Flamm, and J. Q. Kang. 2024.
'Modulating Endoplasmic Reticulum Chaperones and Mutant Protein
Degradation in GABRG2(Q390X) Associated with Genetic Epilepsy with
Febrile Seizures Plus and Dravet Syndrome', Int J Mol Sci, 25.
Pullen, L. C., N. Bott, C. McCanless, A. Revana, G. Sevinc, C. Gorman, A. Duncan, S. Poliquin, A. C. Pfalzer, K. Q. Schmidt, E. R. Wassman, C. Chapman, and M. Picone. 2024. 'Use of Basket Trials to Solve Sleep Problems in Patients with Rare Diseases', Clocks Sleep, 6: 656-67.
Shen, W., C. Flamm, A. J. Delahanty, E. Casteel, M. Biven, M. B. DeLeeuw, S. Poliquin, G. Nwosu, K. Randhave, and J. Q. Kang. 2024. '4-Phenylbutyrate promoted wild-type γ-aminobutyric acid type A receptor trafficking, reduced endoplasmic reticulum stress, and mitigated seizures in Gabrg2(+/Q390X) mice associated with Dravet syndrome', Epilepsia, 65: 204-17.
Shen, W., G. Nwosu, M. Honer, J. Clasadonte, S. Schmalzbauer, M. Biven, K. Langer, C. Flamm, S. Poliquin, F. Mermer, S. Dedeurwaerdere, M. C. Hernandez, and J. Q. Kang. 2024. 'γ-Aminobutyric acid transporter and GABA(A) receptor mechanisms in Slc6a1(+/A288V) and Slc6a1(+/S295L) mice associated with developmental and epileptic encephalopathies', Brain Commun, 6: fcae110.
2023
Kalvakuntla, S., M. Lee, W. K. Chung, S. Demarest, A. Freed, K. J. Horning, T. J. Bichell, S. T. Iannaccone, and K. Goodspeed. 2023. 'Patterns of developmental regression and associated clinical characteristics in SLC6A1-related disorder', Front Neurosci, 17: 1024388.
Nwosu,
G. I., W. Shen, K. Zavalin, S. Poliquin, K. Randhave, C. Flamm, M.
Biven, K. Langer, and J. Q. Kang. 2023. 'GABA(A) Receptor β3 Subunit
Mutation N328D Heterozygous Knock-in Mice Have Lennox-Gastaut Syndrome',
Int J Mol Sci, 24.
Pepe, G., L. Capocci, F. Marracino, N. Realini, P. Lenzi, K. Martinello, T. F. Bovier, T. J. Bichell, P. Scarselli, C. Di Cicco, A. B. Bowman, F. A. Digilio, S. Fucile, F. Fornai, A. Armirotti, R. Parlato, A. Di Pardo, and V. Maglione. 2023. 'Treatment with THI, an inhibitor of sphingosine-1-phosphate lyase, modulates glycosphingolipid metabolism and results therapeutically effective in experimental models of Huntington's disease', Mol Ther, 31: 282-99.
Sullivan, K. R., S. M. Ruggiero, J. Xian, K. M. Thalwitzer, R. Ali, S. Stewart, M. Cosico, J. Steinberg, J. Goss, A. C. Pfalzer, K. J. Horning, N. Weitzel, S. Corey, L. Conway, C. S. Rigby, T. J. Bichell, and I. Helbig. 2023. 'A disease concept model for STXBP1-related disorders', Epilepsia Open, 8: 320-33.
Tjeertes, J., C. A. Bacino, T. J. Bichell, L. M. Bird, M. Bustamante, R. Crean, S. Jeste, R. W. Komorowski, M. L. Krishnan, M. T. Miller, D. Nobbs, C. Ochoa-Lubinoff, K. A. Parkerson, A. Rotenberg, A. Sadhwani, M. D. Shen, L. Squassante, W. H. Tan, B. Vincenzi, A. C. Wheeler, J. F. Hipp, and E. Berry-Kravis. 2023. 'Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS)', J Neurodev Disord, 15: 22.
Whittaker,
D. S., L. Akhmetova, D. Carlin, H. Romero, D. K. Welsh, C. S. Colwell,
and P. Desplats. 2023. 'Circadian modulation by time-restricted feeding
rescues brain pathology and improves memory in mouse models of
Alzheimer's disease', Cell Metab, 35: 1704-21.e6.
2022
Mermer, F., S. Poliquin, S. Zhou, X. Wang, Y. Ding, F. Yin, W. Shen, J. Wang, K. Rigsby, D. Xu, T. Mack, G. Nwosu, C. Flamm, M. Stein, and J. Q. Kang. 2022. 'Astrocytic GABA transporter 1 deficit in novel SLC6A1 variants mediated epilepsy: Connected from protein destabilization to seizures in mice and humans', Neurobiol Dis, 172: 105810.
Nwosu,
G., F. Mermer, C. Flamm, S. Poliquin, W. Shen, K. Rigsby, and J. Q.
Kang. 2022. '4-Phenylbutyrate restored γ-aminobutyric acid uptake and
reduced seizures in SLC6A1 patient variant-bearing cell and mouse
models', Brain Commun, 4: fcac144.
Poliquin,
S., and J. Q. Kang. 2022. 'Disruption of the Ubiquitin-Proteasome
System and Elevated Endoplasmic Reticulum Stress in Epilepsy', Biomedicines, 10.
2021
Mermer,
F., S. Poliquin, K. Rigsby, A. Rastogi, W. Shen, A. Romero-Morales, G.
Nwosu, P. McGrath, S. Demerast, J. Aoto, G. Bilousova, D. Lal, V. Gama,
and J. Q. Kang. 2021. 'Common molecular mechanisms of SLC6A1
variant-mediated neurodevelopmental disorders in astrocytes and
neurons', Brain, 144: 2499-512.
Poliquin,
S., I. Hughes, W. Shen, F. Mermer, J. Wang, T. Mack, D. Xu, and J. Q.
Kang. 2021. 'Genetic mosaicism, intrafamilial phenotypic heterogeneity,
and molecular defects of a novel missense SLC6A1 mutation associated
with epilepsy and ADHD', Exp Neurol, 342: 113723.
Willgoss,
T., D. Cassater, S. Connor, M. L. Krishnan, M. T. Miller, C.
Dias-Barbosa, D. Phillips, J. McCormack, L. M. Bird, R. D. Burdine, S.
Claridge, and T. J. Bichell. 2021. 'Measuring What Matters to
Individuals with Angelman Syndrome and Their Families: Development of a
Patient-Centered Disease Concept Model', Child Psychiatry Hum Dev, 52: 654-68.
Weston,
K. P., X. Gao, J. Zhao, K. S. Kim, S. E. Maloney, J. Gotoff, S. Parikh,
Y. C. Leu, K. P. Wu, M. Shinawi, J. P. Steimel, J. S. Harrison, and J.
J. Yi. 2021. 'Identification of disease-linked hyperactivating mutations
in UBE3A through large-scale functional variant analysis', Nat Commun, 12: 6809.
2020
Wang,
J., S. Poliquin, F. Mermer, J. Eissman, E. Delpire, J. Wang, W. Shen,
K. Cai, B. M. Li, Z. Y. Li, D. Xu, G. Nwosu, C. Flamm, W. P. Liao, Y. W.
Shi, and J. Q. Kang. 2020. 'Endoplasmic reticulum retention and
degradation of a mutation in SLC6A1 associated with epilepsy and
autism', Mol Brain, 13: 76.
Shen, W., S. Poliquin, R. L. Macdonald, M. Dong, and J. Q. Kang. 2020. 'Endoplasmic reticulum stress increases inflammatory cytokines in an epilepsy mouse model Gabrg2(+/Q390X) knockin: A link between genetic and acquired epilepsy?', Epilepsia, 61: 2301-12.
2019
Han, J., T. J. Bichell, S. Golden, I. Anselm, S. Waisbren, C. A. Bacino, S. U. Peters, L. M. Bird, and V. Kimonis. 2019. 'A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome', Orphanet J Rare Dis, 14: 232.
Shi,
Y. W., Q. Zhang, K. Cai, S. Poliquin, W. Shen, N. Winters, Y. H. Yi, J.
Wang, N. Hu, R. L. Macdonald, W. P. Liao, and J. Q. Kang. 2019.
'Synaptic clustering differences due to different GABRB3 mutations cause
variable epilepsy syndromes', Brain, 142: 3028-44.
