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Young Investigator Profile: Mohammed Uddin

Postdoctoral Fellow, The Hospital for Sick Children

Recommended by Steve Scherer, The Hospital for Sick Children

NEW YORK (GenomeWeb) – As a PhD student, Mohammed Uddin studied genomic hotspot regions using next-generation sequencing and other genomic tools. As these regions have been linked to autism spectrum and other neuropsychiatric disorders, when Uddin started searching for a postdoc position he looked for one that focused on autism.

Now in Steve Scherer's lab at The Hospital for Sick Children, Uddin is studying autism from a variety of angles. He's analyzing large datasets, including genomic data collected by sequencing the genomes of children with autism, genetic mutation data gleaned from blood samples, and gene expression data obtained from post-mortem brains.

"These large datasets require different ways of looking at things, not just the naive way that most people do," Uddin told GenomeWeb. "So I try to implement my version of the analysis."

The obstacle facing much of autism research, he added, is that the tissue researchers most want to study — the brain — is mostly inaccessible. Instead, they rely on analyzing blood samples from autistic children, even though there's ample evidence that gene expression varies between the blood and the brain. Another recent option has been to analyze neurons grown in the lab from stem cells, but there are also caveats there, Uddin noted, as lab-grown tissue isn't exactly the same as in vivo tissue.

Uddin added that he'll soon be looking for an academic position and, as a PI he wants to continue to focus on brain-related research from both a basic science and disease perspective.

"I would like to involve myself into neuropsychiatric diseases in general, not just autism. But everything that is related to brain… will be the main key for my future career or lab," he said.

Paper of note

Uddin was the first author on a paper appearing in Nature Genetics last year. In it, he and his colleagues reported combining data on rare mutations linked to autism spectrum disorder and transcriptomic data from developing brains.

From this, they found that certain critical exons — ones that are usually more highly expressed in the brain and are likely important for brain development — are more likely to have accumulated rare mutations in people with autism, as compared to their unaffected siblings. This, the researchers said, indicates that exons under purifying selection that are expressed in the brain should be examined for possible involvement in autism and related disorders.

"It was a very good opportunity to work on a dataset like this, and it just introduced a new type of analysis by combining these two types of data," Uddin said.

Looking ahead

The next decade will involve "a lot of head scratching," Uddin said. Researchers have a lot of the whole-genome sequencing data they've been waiting for, but they might not get the results they've been dreaming of. Rather, he predicted that while that data will explain, for instance, the cause of some kids' autism, it might not help elucidate the cause of other kids' autism.

Instead, he said that researchers would have to dig even deeper and also consider the role of, say, epigenetics in disease.

"These are the things we have to think really hard about," he added.

And the Nobel goes to…

If Uddin were to take home the Nobel Prize in a few years' time, he'd like it to be for uncovering the interplay between genetics and the development of cognition.

This is the fifth in a series of Young Investigator Profiles for 2015 that will appear on GenomeWeb over the next few months.