Researcher Profile: Joseph Gleeson, M.D.

Joseph Gleeson, M.D. is a faculty member at the University of California San Diego School of Medicine, and has been an attending physician at Rady Children’s Hospital San Diego since 1999. His research group is interested in the causes of autism and developing new treatments. Gleeson graduated from the University of Chicago Pritzker School of Medicine, and then trained in pediatrics, neurology, and neurogenetics at Boston Children’s Hospital and Harvard Medical School. He has a Research Match project that will open to the Simons Searchlight community in May/June 2021.

We interviewed Joseph Gleeson about his
Research Match project

What is the idea behind your project?

Over the last 10 years, we have learned that autism can be caused by a genetic change in genes that are important for neurological development. We have learned this through research done by the Simons Foundation, the National Institutes of Health, and other international groups.

These genetic changes seem to come from nowhere, meaning that they are found in the child, but not in the genetic information from either mother or father. But, sometimes the genetic change can be detected in the parents through modern scientific techniques. That’s led us to this project that we’re doing right now in collaboration with the Simons Foundation, particularly with Simons Searchlight.

The goal of this project is to find the roots of these genetic changes by looking at the sperm cells from the father. This is based on new research that suggests that genetic changes like this may be hiding within sperm cells. Sometimes they are present in the egg cells of the mother, but we do not have easy access to them. It is important to know that there is nothing that a parent does to cause these genetic changes to occur.

What question will your project answer?

We think that genetic changes that result in autism may be found within sperm cells, and are then transmitted to the child. Our studies suggest that between 10 and 30 percent of cases where there’s a new genetic change in the child, we can see evidence of the genetic change in the father. In a father with no symptoms, these genetic changes are not detected in the father’s blood sample or the saliva sample that was collected.

The goal of our project is to collect sperm samples from men of children who have autism and to find out if the same genetic change is also found in the sperm. We want to determine how often these genetic changes are present in the sperm samples. This could help us to understand the likelihood of men having a child with a genetic condition associated with autism.

We need Simons Searchlight’s help to do this because this project involves families with a child who has a genetic diagnosis in which the genetic change in the child is not present in samples from the parents.

Through this study, we will be able to tell you if the genetic change that’s considered new in a child is also found in sperm from the father. This study will help us to understand how often these genetic changes occur in fathers of children with autism, and whether certain genetic changes are more likely to be found in sperm.

Our hunch is that there are certain genes where a genetic change, if it were to occur in the sperm, might cause those sperm to have some sort of advantage over other sperm in the testes. That advantage might be that they grow faster. They might be more likely to fertilize an egg. And while we don’t actually know this right now, we can learn more by having families participate.

Where have you been recruiting for this project, and how does Simons Searchlight Research Match provide a unique opportunity?

We have been recruiting as much as possible from Simons Foundation, where there has been a longstanding effort to perform genetic sequencing on children with autism and their parents. The discovery of these new genetic changes, called de novo changes, was a major accomplishment for the Simons Foundation and for the autism community. The Simons Searchlight cohort seems to be a perfect fit for us because there will be a lot of families with identified genetic changes, and that will help us to make discoveries faster.

What are the project’s inclusion criteria?

The family must have a child who has an autism diagnosis and is living within the U.S. We do not exclude families that have more than one child with the genetic condition. If there are two children with autism in the same family, that can be a clue that the genetic change is hiding in the sperm.

Both parents must be available to provide a saliva sample. The father is asked to provide a sperm sample, and that’s all done through the mail, free to participants. The kit will include a FedEx Clinical Pak with a pre-paid overnight shipping label to send the samples back to the lab. 

Once a family agrees, we’ll give them a call to make sure that they have all the information they need to agree to participate in the study.

Finally, it is important that the fathers have not had any surgical procedures on their reproductive organs. There are a lot of men who are ineligible because they’ve had a vasectomy or testicular resections.

To thank you for your participation, we provide an Amazon gift card for twenty dollars.

What are the participation steps?

You will receive an email from Simons Searchlight inviting you to participate. If you agree, Simons Searchlight will let us know, and a member of my lab at the University of California will reach out to you. We will send you an envelope with information and items to collect all the samples, which can be mailed back to us. We will call you, and then you can expect to receive some information back within about six months.

If we have any problems, such as an issue with a sample, or if we are not able to extract the genetic information from the sample, we’ll ask you to provide another sample. This is rare, but it does happen. Our ultimate goal is to work with every family to uncover answers to the questions we have.

How can this be beneficial for families with neurodevelopmental conditions?

Families in our study that are considering having more children may benefit from participation. We can let you know the chance of having another child with this condition. We’ve helped other families to answer this question, and that gives the couples a lot of information for their reproductive planning.

For families that are done having children, you already know that these are brand new genetic changes, meaning that this study won’t necessarily benefit you directly, as far as we know. We hope to learn if some genetic changes are more likely to be found in sperm.