19 - Syngap Researcher spotlight: Dr Gavin Rumbaugh, Scripps Research Institute

Dr. Gavin Rumbaugh is a neuroscientist at Scripps Research Institute in Jupiter, Florida. His laboratory focuses on how synaptic connection and neural circuitry contribute to memory, cognition, and behavioral adaptations; more specifically, in comprehension of the genetic mechanism of neurodevelopmental disorders. The Rumbaugh laboratory has been actively pursuing therapeutic pathways to recover disrupting synaptic function and circuit connectivity caused by SynGap 1 mutation.

Dr. Rumbaugh has authored at least a dozen papers on Syngap to date, including one that gives us reason to believe that our patients can be helped by a theraputic.  This is better explained in this articles from AAAS.

Dr. Gavin Rumbaugh worked with Dr. Rick Hunganir during his postdoctoral years when he studied the basic science of how SynGAP protein regulates synaptic function. At the time, SynGAP 1 was a gene, but rare SynGAP 1 related disorders have not been identified in human patients.  He experienced a “powerful change in his career” after meeting his first SynGAP1 patient and devoted his time on SynGAP translational research in his own laboratory to discover pharmaco-therapeutic for his SynGAP patients from then on.  

SynGAP Research Fund has the privilege to gain some insights of what Dr. Gavin is working on. His interview below:

1. Can you tell us a little about you and how did you get interested in SynGAP mutation in the first place?

I studied Syngap1 function as a postdoc in an effort to understand how it generally regulated synapse function. Very basic science. The year I started my own lab, Michaud’s group identified the original Syngap1 patients. Overnight, I re-directed my lab to understand how the brain is impacted by Syngap1 haploinsufficiency. We went on to publish the original Syngap1 mouse modeling studies.

2. What are the highlights of your research recently?

We are working hard on two fronts.

First, using screening methods, we are trying to find drug-like small molecules that regulate SynGAP protein expression in neurons expressing Syngap1 haploinsufficiency. These studies will hopefully identify new drugable pathways to regulate SynGAP expression in patients. I call these studies searching for “Plan B” and “Plan C”, with ASOs being plan A!  (See section 3 of this blog for more on ASOs)

Second, we are using animal models to understand the origins of abnormal behaviors common to Syngapians. We want to understand how the Syngap1 haploinsufficient brain functions to produce behaviors that look like high pain threshold (lack of defensive behaviors), risky behaviors (moving/walking into dangerous situations), and tantrums/challenging behavior (triggered aggressive behaviors). We suspect that these behaviors are generated by brain mechanisms that are unrelated to seizure. In order to find effective treatments for the difficult behaviors, we need to first understand the biological origins.  

3. What are the obstacles if any with your research?

Time and money. Never enough of either.  (Dr. Rumbaugh is an SRF grantee, with Dr. Llamosas as an SRF Fellow.)

4.  What are you most excited relates to SynGAP research in the near future?

That more and more labs are starting to study Syngap1. We need a broad and interactive scientific community if we are going to find safe and effective therapies for Syngapians.  

Gavin giving a presentation at Scripps in 2019 regarding his work on SynGAP.

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