BHSU graduate Jake Miller is researching treatment options for a fatal pediatric neurodegenerative disease.
For Black Hills State University graduate Jake Miller, it’s not only the science behind genetic diseases that he’s passionate about, it’s the faces behind these diseases.

“As a researcher, you see these families and how this disease affects their lives – it’s really powerful to see that,” he said. Miller recently returned to BHSU to discuss his research with BHSU students and faculty.

Miller, who graduated from BHSU in 2009 with a biology and chemistry degree, has been working in Dr. David Pearce’s lab at the Sanford Children’s Health Research Center in Sioux Falls since 2010 when he did a summer medical school research fellowship. He is continuing his research with Dr. Pearce through the M.D./Ph.D. program at The University of South Dakota, Sanford School of Medicine.

Miller’s research focuses on Batten disease, an incurable and eventually fatal pediatric neurodegenerative disease. Batten disease belongs to a group of neurodegenerative disorders known as neuronal ceroid lipofuscinoses (NCL), which all share similar symptoms but are distinguished by different gene mutations and the age at which the symptoms appear.

Batten disease, the juvenile form of NCL, is the most common inherited childhood neurodegenerative disease although still relatively rare – occurring in 2 to 4 out of 100,000 births in the United States. Symptoms of Batten disease usually appear around the age of five and begin with vision loss. The child continues to worsen experiencing seizures, difficulty walking and swallowing, dementia and blindness, Miller said.

“It’s really devastating. Every single one of these disorders will lead to premature death,” Miller said.

And the juvenile form of NCL occurs from a single defective gene – CLN3. Currently there are no treatments that will slow the progression of the disease, but that’s what Miller hopes to change.

Each person inherits one copy of each gene from each parent – so all humans have two copies of each gene. If a person has only one defective copy of CLN3 they will not have the disease because they have a backup healthy copy of the gene. A person is diagnosed with Batten disease when they inherit two bad copies of the CLN3 gene.  

Each type of NCL is the result of mutations in the genes that encode different types of proteins, according to Miller. While the different forms of NCL involve different proteins, Miller said they believe they are all involved in the same pathway which is why the NCL diseases all have similar characteristics.

For example, a dysfunction of the Palmitoyl ProteinThioesterase 1 or PPT1 protein, an essential lysosomal protein in the nervous system, results in the infantile NCL.

All NCLs have nonsense mutations, Miller said. The nonsense mutation converts a codon that encodes an amino acid into a stop codon, which terminates the reading of the messenger RNA (mRNA). The result is a protein product that is shortened, incomplete and usually nonfunctional.

Miller is researching the affect of certain drugs that allow the protein product to fully form and become a complete, functioning protein.

“In the majority of the research, we have been using human cell lines derived from Batten disease patients,” Miller said. “We will continue that research and test the drugs using two mouse models with Batten disease.”

Miller will finish his doctorate in the spring 2014. He will then finish his last two years of medical school and graduate in 2016. Miller plans on pursuing a career where he can continue his research in genetic diseases.

He credits much of his success so far to his undergraduate work at BHSU. “My research as an undergraduate as well as with the Honors program at BHSU gave me an edge in my medical school classes and PH. D research. I was extremely well prepared with my ability as far as doing things in the lab, as well as writing and reading papers,” he said.

At BHSU, Miller was involved in several research projects as a Biomedical Research Infrastructure Network undergraduate research fellow at BHSU’s Center for the Conservation of Biological Resources (CCBR) and the Western South Dakota DNA Core Facility.