Instructor, Harvard Medical School
Understanding the molecular and cellular pathophysiology of Neurodevelopmental Disorders using human stem cell models.
Brief Research Description
I am a physician scientist with a unifying interest in the genetic causes underlying the development of neural circuits and the conditions that arise when these mechanisms are pathologically disrupted, especially behavioral and cognitive disorders. Due to the enormous genetic complexity underlying ASD, I have approached my research questions from the perspective of rare genetic syndromes with high rates of ASD. Throughout my post-doctoral research, I have been mostly focusing on Tuberous Sclerosis Complex (TSC) because it has the dual advantage of conferring a significant risk to developing ASD and the downstream pathways are relatively well understood. I have developed projects on the intrinsic dysfunction of human neurons in TSC and found alterations in RNA binding and activity dependent processes. In addition, I am interested in potential non-cell autonomous effects in TSC leading to formation of cortical dysplasia.
Key Publications (PMCIDs)
Increased degradation of FMRP contributes to neuronal hyperexcitability in tuberous sclerosis complex.
Winden KD, Pham TT, Teaney NA, Ruiz J, Chen R, Chen C, Sahin M.
Cell Rep. 2023 Aug 29;42(8):112838. PubMed Central PMCID: PMC10529098
Loss of Tsc1 in cerebellar Purkinje cells induces transcriptional and translation changes in FMRP target transcripts.
Dalal JS*, Winden KD*, Salussolia CL, Sundberg M, Singh A, Pham TT, Zhou P, Pu WT, Miller MT, Sahin M.
Elife. 2021 Jul 14;10 PubMed Central PMCID: PMC8279760.
Biallelic Mutations in TSC2 Lead to Abnormalities Associated with Cortical Tubers in Human iPSC-Derived Neurons.
Winden KD, Sundberg M, Yang C, Wafa SMA, Dwyer S, Chen PF, Buttermore ED, Sahin M.
J Neurosci. 2019 Nov 20;39(47):9294-9305. PubMed Central PMCID: PMC6867816.
Abnormal mTOR Activation in Autism.
Winden KD, Ebrahimi-Fakhari D, Sahin M
Annu Rev Neurosci. 2018 Jul 8;41:1-23. PubMed PMID: 29490194.
