16 – Understanding SynGAP1

Event Time

December 4, 2020 at 4:30 pm


Here are our introductory comments: 

We are very excited to continue the SRF webinar series. The goals of the series are:

  • getting you closer to the science 
  • making you aware of the research that is been done and the opportunities to participate
  • and empowering your communications with clinicians 

We also want to remind you of our next webinar in the series with Dr. Connie Smith-Hicks on “Biomarker Development a path towards clinical trial readiness in SYNGAP1” scheduled later this week, August 5 at 2 pm ET.

The talk today is “What is epigenetics and how can it accelerate therapies for SYNGAP?”

Today’s speaker is Dr. Elizabeth Heller, who is an Assistant Professor of Pharmacology at UPENN (University of Pennsylvania) and also a SYNGAP caregiver. Her story is unique as her inspiration to research SYNGAP is very personal. Her niece Ruby Heller, now 14, was diagnosed with SYNGAP in 2016. At that time her interest as a neuroscientist regained a focus on SYNGAP. She has first-hand knowledge of SYNGAP as a disease. She’s close to her niece and understands how SynGAP turns a family’s life upside down. 

Dr. Heller received her PhD in molecular biology from The Rockefeller University. She then studied the epigenetics of drug addiction and depression at the Icahn School of Medicine at Mount Sinai. In 2016 she returned to UPENN as an Assistant Professor. 

The Heller Lab studies the mechanisms by which epigenome remodeling regulates neuronal gene function and behavior. Her lab is uniquely suited to carry out epigenetic research in SYNGAP. It consists of experts across neuroscience and genetics, including chromatin biochemistry, behavioral neuroscience, next-generation sequencing, machine learning, and CRISPR/Cas9-directed epigenetic editing. Her research is supported by membership in the Penn Epigenetics Institute and the Institute for Translational Medicine and Therapeutics.

I want to quote Dr. Heller’s owns words “My niece has given me extraordinary gifts in terms of my personal growth as a caregiver and communicator, and I am ever grateful to be one of her Special People. It is a privilege to enter the Syngap1 research field as a molecular and behavioral neuroscientist”.

We as a group felt privileged and lucky that Dr. Heller is going to dedicate her lab to find what is outside of the gene –of how everything else in the genome affects the regulation of a gene. This is an area of research that hasn’t been touched in SYNGAP that may hold another gigantic clue or clues and can be a big part of the puzzle.

After this brief introduction, I want to let you know a recorded version of this webinar will be available on the SRF website.

By the end of this presentation, you will have an opportunity to get your questions answered. We’d love to hear from you – please write your question in the chat.

For those of you just joining us, welcome and our talk today “What is epigenetics and how can it accelerate therapies for SYNGAP?” by Dr. Elizabeth Heller neuroscientist and SYNGAP caregiver.

Webinar Overview

Dr. Elizabeth Heller studies epigenetic reprogramming and its role in neuropsychiatric and developmental disease at UPenn. Her niece Ruby has SYNGAP1, and while her lab normally focuses on drug behavior, her lab is now focused on discovering how the SYNGAP1 gene is regulated. She starts by talking about the epigenome, which refers to the structure of DNA and regulation of DNA based on modifications to that structure. Dr. Heller then talks about how her lab uses the epigenome and neuronal activity to uncover the regulation of different SYNGAP1 isoforms. In order to causally link the epigenome to gene expression, she explains how they can use epigenetic editing which regulates the epigenome at one gene. There are many tools for epigenetic editing, but Dr. Heller’s lab has been working on designing and synthesizing guide RNAs that recognize the SYNGAP1 gene promoter. These specific guide RNAs will be used with CRISPR dCas9 technology to alter SYNGAP1 expression. This technique has already been successful in rescuing seizure behavior in animal models with Dravet Syndrome, so it is their hope that they will find success in rescuing SYNGAP1 expression in patients with SYNGAP1.

Other Relevant Publications by Dr. Heller

Stereotaxic Surgery and Viral Delivery of Zinc-Finger Epigenetic Editing Tools in Rodent Brain

Viral Expression of Epigenome Editing Tools in Rodent Brain Using Stereotaxic Surgery Techniques