The concept for the Center of Biomedical Research Excellence in Diabetes at the University of Hawaii John A. Burns School of Medicine began taking shape about five years ago.

Amid an ongoing alarming rise in prediabetes and type 2 diabetes in the islands, “JABSOM sought to bring experts together to look at the complex interplay of lifestyle, genetics, gender and the social determinants of health in triggering and modifying this condition,” said Mariana Gerschenson, a professor of cell and molecular biology and the med school’s director of research and graduate education.

Thanks to an $11 million National Institutes of Health research grant awarded this month, Gerschenson is now also serving as director of the new center, which will be housed at the school’s biomedical science building. “This new grant brings additional federal (NIH) resources to Hawaii to provide a base for developing innovations and supporting scientists who will lead the discovery team with a focus on the specific needs of the people of Hawaii,” she said.

Prediabetes and type 2 diabetes affect nearly 600,000 people in the islands — roughly 1 in 2 Hawaii residents — and Native Hawaiians and other Pacific Islanders are two times more likely to have diabetes than other ethnic groups here.

A second-generation researcher, Gerschenson’s childhood memories include running around barefoot in her father’s lab at the University of California Los Angeles, where he conducted diabetes research.

“I remember equipment being big in the 1960s and ‘70s. Nowadays, with the advances in electronics and technology, lab equipment is quite small; think of old telephones with cords versus our hand-held phones now. We also used to make all our solutions from scratch and now we buy everything already made, so we now have lots of cake mixes in the laboratory.”

After earning a bachelor’s degree in psychology and a doctorate in experimental pathology at Colorado universities, Gerschenson studied genetics and molecular medicine at Emory School of Medicine in Atlanta. About 15 years ago, she was recruited to the UH Pacific Biomedical Research Center and then to JABSOM.

Since her father’s decades-ago work at UCLA, she said, “The times have changed and we know a lot more but there are still lots of questions to be answered when it comes to why do some people become prediabetic and why … (roughly) 25 percent become diabetic.”

Question: Do investigators point to anything in particular as responsible for touching off increases in diabetes cases?

Answer: The growing burden of diabetes in the United States is attributed in part to the aging of the general populations as a whole, an increase in the percentage of minorities (with a cultural or genetic risk factors) … and the fact that people with diabetes and prediabetes are living longer. … Both diabetes and obesity are higher among racial and ethnic minorities in the U.S.

Global predictions for diabetes prevalence by 2030 are that 366 million people will have the disease, representing a doubling of diabetes cases since 2000.

Moreover countries with the highest prevalence of diabetes in 2030 are predicted to be India (79.4 million), China (42.3 million) and the U.S. (30.3 million). Hawaii is at the crossroads between the U.S. continent and China and India; Hawaii thus offers a multi-ethnic “hot spot” region for investigating the molecular complexities underlying diabetes and prediabetes.

… Worrisome for future generations is the observation that the prevalence of obesity in adolescents and children has increased dramatically over the last three decades in the United States.

Q: How significant is the ethnic component in developing diabetes?

A: We know there are ethnic differences associated with the risk for developing prediabetes and diabetes, we just do not know why. We do know that Japanese-Americans and other Asians develop diabetes with much lower BMIs (body mass index) than other high-risk populations.

The underlying mechanism for this seems to be preferential placement of visceral adiposity (i.e., where fat preferentially collects in the body). However, recent studies have also examined pancreatic beta cell defects in secretion and well as beta cell mass in response to ambient insulin resistance.

In Samoans, there is now genetic data suggesting that there is increased fat storage and decreased energy use due to a genetic difference in one regulatory protein called CREB (cAMP response element-binding protein). We will help characterize such mechanisms associated with diabetes risk and seek solutions for high-risk ethnic groups in the Pacific.

Q: What will be happening in the research center during its first few years of operation?

A: The center has four funded research projects. … Project 1 examines the function of transient receptor potential (TRP)A1 activity in the pancreas and other cells and tissues. Project 2 addresses how glucose transport is regulated in adipocytes (fat cells) and skeletal muscle in prediabetes and diabetes.

Project 3 addresses epigenetics (which genes are turned on) and how DNA methylation of genes involved in inflammation contributes to diabetes. Project 4 examines how ATP binding cassette, subfamily C, member 6 (ABCC6) deficiency in liver and kidneys causes an imbalance of circulating calcification inhibitors leading to enhanced medial calcification in diabetes and kidney disease and dyslipidemia (a diabetic complication).

Projects 1, 2, and 4 are all pre-clinical that will help us understand how cell function changes with diabetes, and Project 3 is a clinical study to look at the monocyte inflammatory response and insulin sensitivity in diabetic and non-diabetic participants in Native Hawaiians, Pacific Islanders and other high-risk minority subjects. We will be recruiting volunteers for Project 3.

Q: How difficult was it to secure the grant?

A: It is very competitive to obtain NIH funding for research centers since it is a lot of money and an initial five-year commitment plus the opportunity to apply for another two five-year cycles.

Receipt is based on scientific merit. This means the principal investigator has to be a scientific leader in their field and show the administrative capacity to manage the grant. Additionally, for this center grant, since we are training assistant professors in the diabetes field, you have to demonstrate experience training career scientists and faculty. These grants are peer-reviewed twice by other scientists and by the NIH.

… The University of Hawaii at Manoa can only have three of these grants at one time. JABSOM has three such grants: Pacific Center for Emerging Infectious Disease Research, Institute of Biogenesis Research, and diabetes.

We initially applied in 2014, so I started writing the grant in October 2013 and submitted the first version February 2014 with my research team. … So it has been almost three years since we started. The grant is 550 pages long.

I would like to acknowledge lots of people who made this happen. I want to particularly thank my parents, husband and brothers who … understood that I had to work over the holidays, nights and weekends.

Q: What do you find most challenging/frustrating about your work?

A: The most challenging part of science is obtaining funding, since scientists must always write grants to get funds. The most frustrating part about science is the amount of paperwork and rules; the regulations increase every year, forms change, more monitoring is required, etc. If we could just focus on the science, our job would be perfect.

Q: Most enjoyable?

A: I still love research, including: identifying problems, testing a hypothesis, analyzing data and changing the clinical paradigm. I am specifically interested in mitochondria (batteries of the cell) and how they are involved in prediabetes and diabetes. Our research is solely on clinical specimens, so every discovery we make has a human impact.

I also find teaching and mentoring undergraduate, graduate and medical students and junior faculty in the classroom and research lab very rewarding. In addition, I enjoy being able to help faculty, staff and students while I serve as the director of research and graduate education for the medical school. I am responsible for the strategic planning and development of research at the medical school, research administration activities, and the five graduate (MS and PhD) programs.