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samyounglab @SamYoungLab

Deciphering cellular and molecular mechanisms of synaptic function and impact on neuronal circuit output. Viral vector development and CNS gene therapy.

Joined December 2018
  • Tweets 827
  • Following 487
  • Followers 858
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samyounglab retweeted
Lu-Yang Wang@SynapticTweeter
10 Jul 2024
Delighted to share our new Nature paper: rdcu.be/dNlMQ This works shows a surprising off-target effect of glutamate on another cell death channel, acid sensing ion channels (ASICs). It turns out that glutamate directly binds to ASICs as a positive allosteric modulator

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Amazing findings !! Congrats you and the team
Lu-Yang Wang@SynapticTweeter
10 Jul 2024
Delighted to share our new Nature paper: rdcu.be/dNlMQ This works shows a surprising off-target effect of glutamate on another cell death channel, acid sensing ion channels (ASICs). It turns out that glutamate directly binds to ASICs as a positive allosteric modulator
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samyounglab retweeted
Matt Hill@canna_brain
8 Jul 2024
So for those of you interested in what it was that I took issue with in Hubermans first cannabis podcast, this is the Coles notes of the errors/inaccuracies that I noted. A lot of this is covered in the new episode, but some wont make it through and for others this is the TLDR
Andrew D. Huberman, Ph.D.
@hubermanlab
8 Jul 2024
New Huberman Lab podcast out now: CANNABIS: EFFECTS ON HEALTH & RISKS w/guest @canna_brain •THC, CBD Biology •Cannabis & Psychosis •Is THC addictive? •Are Strain Differences Real or Placebo? •Appetite, Hormones •Dosage Control: Inhaled vs Edible hubermanlab.com/episode/dr-m…
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Love cellular and molecular neuro. We are hiring a staff scientist interested in building framework of molecular principles for accurate sound information encoding and contribution to auditory deficits. unc.peopleadmin.com/hr/posti… Must have background in patch clamp DM or email
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Big news. We are moving. I have officially started as the Director of the Gene Therapy Center, and as a Professor of Pediatrics and Professor of Pharmacology at UNC-Chapel Hill. I am returning “home” to lead the Center where I earned my PhD.
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Amazing paper!!! Congratulations to you and John and the team.
Lu-Yang Wang@SynapticTweeter
20 Jun 2024
Check it out: most beautiful images of vATPase with a surprising partner on live synaptic vesicles from my brilliant colleague John Rubinstein and his team at SickKids Reaearch Institute & University of Toronto! science.org/doi/10.1126/scie…
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Using a “humanized” hCD46 mouse model, we demonstrate these Ad vectors transduce cerebellar cell-types, including Purkinje cells, that are refractory to Ad5 transduction.
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We thank @FamilieSCN2A @scn2agene @cacna1a @ncats_nih_gov @NIH_NINDS @NIDCD @uihealthcare @uiowaOUR funding this research We thank @UIowaACB @UIowaNeuro @UIowaResearch for creating an amazing environment for carrying out high risk high reward research
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Finally, I want to thank Dr. Emre Kul, Uchechi Okorafor @MissSafie and the rest of the team for taking on this immense challenge to solve a fundamental problem in the gene therapy field.
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However, these Ad5 vectors are unable to transduce many neuronal cell types that are dysfunctional in many CNS disorders. The human CD46 (hCD46) receptor is widely expressed throughout the human CNS and is the primary attachment receptor for many Ad serotypes.
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Therefore, to overcome the current limitations of Ad vectors to treat CNS disorders, we created chimeric 1st generation Ad vectors that utilize the hCD46 receptor.
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Viral vector gene therapy has immense promise for treating central nervous system (CNS) disorders. Although adeno-associated virus vectors (AAV) have had success, their small packaging capacity limit their utility to treat the root cause of many CNS disorders.
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Adenoviral vectors (Ad) have tremendous potential for CNS gene therapy approaches. Currently, the most common vectors utilize the Group C Ad5 serotype capsid proteins, which rely on the Coxsackievirus-Adenovirus receptor (CAR) to infect cells.
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For ~25 years Ad vectors had little to no ability to transduce Purkinje cells, until now! Excited to announce our paper in MTMCD @MolTherapy on the development of Ad vectors that transduce Purkinje cells in a humanized mouse model shorturl.at/wyBW5
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The CaV2.1 α1 subunit domain II–III loop and cytoplasmic C-terminus are positive regulators of presynaptic CaV2.1 abundance but do not regulate preference.
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The CaV2 α1 subunit motifs determining the presynaptic CaV2 preference are distinct from abundance.
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We are cranking away to get at this code that determine tpresynaptic Cav2 subtype specificity as it is a the keystone that determines how neuronal circuits transmit information in health and disease
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Presynaptic CaV2 subtype abundance regulates neuronal circuit properties, although the mechanisms regulating presynaptic CaV2 subtype abundance and preference remain enigmatic.
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The CaV α1 subunit determines subtype and contains multiple motifs implicated in regulating presynaptic subtype abundance and preference.
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