Current Research Interests:
The Uhler laboratory studies the role of neuronal signaling in the context of human neurologic and psychiatric disorders. We have developed a number of tools to study gene expression in neurons derived from mouse and human stem cells. We derive various neuronal populations using expression of neurogenic transcription factors to produce excitatory and inhibitory neurons. Using these neurons, we have defined signal transduction cascades for fibroblast growth factors (FGFs) and identified genes regulated by FGFs that alter neuronal function. We are currently deriving neuronal populations from patients with major depressive disorder (MDD) to determine if FGF signaling is altered in MDD. We are also characterizing the role of novel signaling proteins in the regulation of synaptic activity of human neurons in vitro.


Asynchronous neuronal activity of 6 day old neurons indicated by calcium imaging on multi-electrode arrays.

Highly synchronous neuronal activity of 30 day old neurons by calcium imaging after FGF2 treatment.
Selected Publications
Gupta S, M-Redmond T, Meng F, Tidball A, Akil H, Watson S, Parent JM, Uhler MD.
Fibroblast growth factor 2 regulates activity and gene expression of human post-mitotic excitatory neurons.
J Neurochem, 2018. 145(3): p. 188-203.
Tidball AM, Dang LT, Glenn TW, Kilbane EG, Klarr DJ, Margolis JL, Uhler MD, Parent JM.
Rapid Generation of Human Genetic Loss-of-Function iPSC Lines by Simultaneous Reprogramming and Gene Editing.
Stem Cell Reports, 2017. 9(3): p. 725-731.
Ramakrishnan SK, Zhang H, Takahashi S, Centofanti B, Periyasamy S, Weisz K, Chen Z, Uhler MD, Rui L, Gonzalez FJ, Shah YM.
HIF2alpha Is an Essential Molecular Brake for Postprandial Hepatic Glucagon Response Independent of Insulin Signaling.
Cell Metab, 2016. 23(3): p. 505-16.
Huang HS, Redmond TM, Kubish GM, Gupta S, Thompson RC, Turner DL, Uhler MD.
Transcriptional regulatory events initiated by Ascl1 and Neurog2 during neuronal differentiation of P19 embryonic carcinoma cells.
J Mol Neurosci, 2015. 55(3): p. 684-705.
Yang H, Li G, Wu JJ, Wang L, Uhler M, Simeone DM.
Protein kinase A modulates transforming growth factor-beta signaling through a direct interaction with Smad4 protein.
J Biol Chem, 2013. 288(12): p. 8737-49.
Huang HS, Turner DL, Thompson RC, Uhler MD.
Ascl1-induced neuronal differentiation of P19 cells requires expression of a specific inhibitor protein of cyclic AMP-dependent protein kinase.
J Neurochem, 2012. 120(5): p. 667-83.
Zhang H1, Deo M, Thompson RC, Uhler MD, Turner DL.
Negative regulation of Yap during neuronal differentiation.
Dev Biol, 2012. 361(1): p. 103-15.
|