Pejmun Haghighi, PhD, Professor

Tuning neural function as it relates to aging and age-related diseases

A growing consensus suggests that stability and homeostasis in synaptic growth and function may be key in maintaining the health of neural circuits, and as such, disruption in regulatory mechanisms that control synaptic homeostasis may lead to developmental and neurodegenerative nervous system diseases. My research program investigates the molecular mechanisms that underlie synaptic homeostasis. In particular, we are interested in learning how retrograde signaling cascades participate in this process. 

My laboratory has been identifying and characterizing genes and mechanisms that participate in this regulation by exploiting the power of Drosophila genetics in combination with imaging and electrophysiology.  In particular, my group’s success in understanding the basic biology of synaptic function have led us to the identification of the target of rapamycin (TOR) as a critical regulator of synaptic homoeostasis. This finding is of particular interest, since TOR-dependent pathways play a highly conserved role in the regulation of life span in a wide range of organisms from yeast to mice.  We believe that our work will generate important insight into how nervous system function and life span regulation may be mutually modulated.  

Aging and synaptic function:
Based on our findings, we have hypothesized that abnormal synaptic function negatively influences life span in Drosophila. We are addressing this hypothesis by establishing that interference with synaptic transmission can influence life span, while restoring normal synaptic function in mutant combinations with shorter life span can restore normal life span. We are also investigating the role of human disease-related genes in this process.

Postsynaptic translation:
We are interested in identifying mRNAs that are under the control of TOR-dependent postsynaptic translational cascades. We have been using genetic screens as well as biochemical approaches for these studies. 

The role of miRNAs:
Our recent findings suggest that miRNAs may be acting as negative regulators of synaptic strength by limiting the amount of presynaptic neurotransmitter release. We are pursuing this idea by combining genetic and optogenetic approaches to monitor miRNA activity in neurons while manipulating synaptic activity and/or signaling.

Dr. Haghighi received his PhD in Physiology from McGill University in Montreal, Canada, where he also served as an assistant, then associate professor.  In 2010 he received the Ann Wechsler Award for Excellence in Teaching Physiology. Dr. Haghighi’s research was funded in large part, by the Canadian Institute for Health Research.  He was a postdoctoral fellow in the lab of Corey Goodman, PhD, at the University of California Berkeley. 

phaghighi@buckinstitute.org 
Phone: 415-209-2205

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Recent Publications

2016

Jay Penney, Kazuya Tsurudome... A Pejmun Haghighi "LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction." Nat Commun 7 12188
Grant Kauwe, Kazuya Tsurudome... A Pejmun Haghighi "Acute Fasting Regulates Retrograde Synaptic Enhancement through a 4E-BP-Dependent Mechanism." Neuron 92:6 1204-1212
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