Fall 2016
Super-Resolution Microscope Allows Study of Subcellular Structures

synapse: University of Nevada, Reno School of Medicine

Iain Buxton, Ph.D.

Microscopic Discovery

Iain Buxton, Pharm.D., explains the benefits of his department's new super-resolution microscope. Photo by Anne McMillin.

Yields Findings for Breast Cancer Research

Story by Anne McMillin, APR

Through a settlement brokered by the State of Nevada Attorney General's Office, approximately $3.8 million is available to the University of Nevada, Reno School of Medicine for research projects aimed at improving women's health in Nevada.

The State of Nevada obtained the settlement with pharmaceutical companies Wyeth, Pfizer and Pharmacia & Upjohn relating to claims regarding postmenopausal hormone therapy products.

The funds are distributed by the Attorney General's Office with half the available research funds going to UNR Med faculty in Reno and Las Vegas and the other half going to University Medical Center of Southern Nevada.

Through the process of submitting grant proposals, UNR Med faculty members are able to access settlement funds to support research studies on women's health.

The School of Medicine's pharmacology department is heavily involved in research relating to women's health. Iain Buxton, Pharm.D., pharmacology department chair, purchased a super-resolution microscope, the first of its kind for Nevada, which is being used to accelerate the discovery of treatments for human disease. This microscope enables scientists to study subcellular structures in the greatest detail using fluorescence imaging.

The super-resolution microscope provides researchers the capability of examining cells at a level that reveals details of molecular interactions otherwise unseen. Such discoveries accelerate the development of new approaches to understand and treat disease, and can attract pharmaceutical companies interested in supporting clinical trials.

Buxton is the principal investigator on research projects involving breast cancer and pre-term birth at UNR Med.

In his research efforts regarding breast cancer, Buxton and his team believe they've cracked the code of breast cancer metastasis; meaning they now understand how that migration works, what tends to trigger tumor growth, and have pinpointed two drugs that when used in combination effectively stop it from happening.

Breast tumor cells migrate to distant sites in the body early in the course of the disease and remain dormant, before they are capable of forming aggressive metastases. Growth of tumor cells as metastatic sites dictates that tumor cells must first develop a capillary blood supply or risk necrosis. What activates dormant cells at metastatic sites to move from a quiescent to aggressive phenotype is not known, but it is believed that a kinase carried by extremely small vesicles called exosomes discovered to be released from cancer cells produces a blood supply at distant sites for cells that can target these sites when they arrive later, and lay dormant before growing as metastases in the future.

"This microscope allows us to visualize an enzyme released by triple-negative breast cancer cells that appears to be the earliest signal from the breast tumor as to where it will later form metastases," Buxton said.

He explained that exosomes encapsulated by the tumor are so small, they are only visible via electron microscope. The super-resolution microscope can employ living cells allowing Buxton's team to see the exosomes to determine if they carry that particular enzyme.

"The benefit is that we can see whether or not the exosomes contain the enzyme. If they do, we have compounds that inhibit that enzyme and others that knock down production of the enzyme product." From that point, commercial development of a neo-adjuvant treatment can be developed to give women a treatment option prior to breast surgery.

To pursue commercial development, Buxton has created ExCyte Therapeutics, a technology-transfer company with the purpose of seeking resources to attract pharmaceutical partners to develop a non-toxic new treatment based on his research findings.

Buxton is also internationally renowned for his research into the causes of preterm labor and has changed the way scientists think about the regulation of uterine function in pregnancy.

Babies delivered prior to full development at term have multiple medical problems that plague these individuals throughout their lifetime. Prematurity explains 75 percent of all fetal morbidity and mortality.

His research lab is exploring contraction-relaxation coupling in the uterine smooth muscle in order to better understand and develop treatments for preterm labor.

The Buxton laboratory is funded by the National Institutes of Health and has attracted numerous extramural grants from groups such as the March of Dimes, the American Heart Association and the Bill and Melinda Gates Foundation.

He has published more than 100 peer-reviewed articles and contributed to three textbooks in pharmacology and therapeutics.

He has received numerous teaching and research awards including the Nevada Business Magazine's 2016 Healthcare Hero (Innovator), UNR Foundation Professor in 2013, the Regents Researcher Award in 2011 and UNR Outstanding Researcher Award in 2008.