King Calcium


Juan Pedraza

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King Calcium

Brij Singh, a biomedical researcher at the University of North Dakota, recently pitched a proposal to the National Institutes of Health, the country’s largest single funder of projects that look for answers to pressing health questions.

That is not unusual.

What is unusual is that Singh scored a second multi-year NIH R01 grant, $1.73 million. That’s no small feat in a fiscally tight and extremely competitive environment.

“The R01 grant is the original and oldest of the NIH’s funding mechanisms, and is arguably the most prestigious,” said Joshua Wynne, vice president for health affairs and dean of the School of Medicine and Health Sciences. “With this grant, Dr. Singh will continue his studies of the control mechanisms involved in the movement of the element calcium across the cell membrane. Calcium is essential for proper cellular function in various tissues, and derangements in its movement may be involved in many diseases such as Sjögren’s syndrome, cancer, Parkinson’s, Alzheimer’s disease, and others.”

“Yes, I feel very fortunate to have received this renewed R01 funding,” said Singh, who’s built a distinguished track record hunting down the precise role of calcium in various diseases and how stem cells may fit into curative strategies to combat these tragic illnesses. “This R01 grant will allow me and my team to probe more deeply into the calcium channel roles in the development of some of these diseases.”

Singh, an associate professor of biochemistry and molecular biology, conducts research on calcium mechanisms in the body that can, if not working properly, lead to diseases such as cancer, Parkinson’s disease, and Sjögren’s syndrome, a salivary gland dysfunction. He focuses on how and why calcium, one of the most important biochemical regulators in the body, works at the cellular level. Singh was on a team of five talented young researchers recruited by UND to contribute to the School of Medicine’s biomedical research effort under a five-year, $10.4 million NIH Center of Biomedical Research Excellence grant.

Parkinson’s disease is a chronic and progressive movement disorder, meaning that symptoms continue and worsen over time, according to the Parkinson’s Foundation (see What is Parkinson's Disease).

About 1 million people in the United States have Parkinson’s. The cause is unknown and there is no known cure.

“Parkinson’s results from the malfunction and death of neurons, the most important cells in the brain,” Singh said. “The goal of my research is to investigate this disease mechanism and others, such as Sjögren’s or dry-mouth syndrome that are triggered by a malfunction in calcium signaling.”

“For over a decade, my research efforts and those of my lab have focused on understanding these calcium signaling mechanisms,” said Singh, who joined the UND faculty in 2003.

“As a postdoctoral fellow at the Medical College of Wisconsin and at the NIH, I studied neurodegeneration — such as the kind that occurs with Alzheimer’s and Parkinson’s — using both molecular and biochemical techniques,” Singh said. “Here at UND, I expanded my research to include the regulation of TRPC1 channels in both neuronal and non-neuronal cells and have established TRPC1 as the ion channel necessary for regulating the precise calcium entry needed for proper functioning of these cells.”

Singh’s research builds logically on his ongoing work that uses specially bred research mice as well as human neurons and human patient samples to decipher the role of calcium in several disease processes.

Singh was one of several UND biomedical researchers to receive the first North Dakota Spirit Faculty Achievement Award, funded by the UND Foundation. That award recognizes significant contributions by faculty in teaching, research and service.

A relatively new area of inquiry for Singh and his team is the role of stem cells in the development and, eventually, the cure for ailments such as dry-mouth syndrome, which can be a direct consequence of radiation therapy for oral and related cancers.

“We’re looking deeper for possible therapies,” Singh said. “With radiation therapy for head and neck cancers, many patients completely lose their ability to salivate, which is essential for digestion,” Singh said. “They suffer a decreased quality of life. We believe that we can introduce stem cells into these glands to regenerate the saliva-producing cells, but we still have a long way to go to accurately define how this would work. One of the problems is that, as many scientists have noted, stem cells and cancer cells do about the same thing: they reproduce rapidly. Some scientists believe that stem cells trigger some kinds of cancer.”

So the challenge is to find ways to get the stem cells to reproduce or regenerate the right kind of cells. That’s the research that UND scientists want to ultimately achieve with this latest NIH R01 support.

“I envision that this research will take at least five years, using mouse models and a lot of work under the microscope,” Singh said.

Among the tools he and his team are using is a new kind of microscope that allows them to observe living tissue, rather than having to prepare specimens from dead tissue. “We get to see what’s going on in a sedated animal, in living cells,” Singh said. “That’s much more useful to us as we can do it in real time.”

Singh’s research has acquired a new urgency because as the Baby Boom population ages, we’re seeing more Parkinson’s, cancers, and other diseases related to aging.

Bottom line, Singh said, is that he’s looking at the role of one molecule — calcium — in health and disease processes.

“Calcium is essential for life,” Singh said. “It’s the key intercellular signaling mechanism: it tells each and every cell and the body what to do. To perform its job, a cell has to get that calcium signal, whether it’s heart muscle cells knowing when to contract, a kidney cell knowing when to filter, or a digestive tract cell knowing when to absorb a nutrient. Everything you do needs calcium.”

Juan Pedrazza

Writer/Editor for University Relations

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