Rudy Juliano, PhD, is the new associate dean for research and graduate education at the UNC Eshelman School of Pharmacy, but he isn’t exactly a new face around the School.

Juliano, who came to the School from the Department of Pharmacology at the School of Medicine, was a longtime instructor in pharmacology courses offered to pharmacy students. He also has collaborated with many faculty members at the School on research projects.

“I was very impressed with the developments at the School of Pharmacy in terms of the evolution of the research efforts, especially in the last few years,” says Juliano, who filled the vacancy left when Dhiren Thakker resigned to focus on other projects at the School. “When Dhiren decided to step down, it just seemed like an interesting opportunity to get re-involved in research administration in a very dynamic atmosphere.”

Juliano is also no stranger to overseeing research and graduate education. He took on those responsibilities when he chaired the Department of Pharmacology from 1987 to 2002. One of Juliano’s duties in his new role is to help faculty land more large, multi-investigator grants.

Cell Receptors and Macromolecular Therapeutics

In addition to his administrative duties, Juliano will also continue his own research, which falls into two general areas—cell receptors and macromolecular therapeutics.

The cell receptor aspect of Juliano’s work looks at receptors and signal transductions in cells. He focuses on integrins, a family of surface receptors that mediate intracellular signals, define cellular shape and mobility, and regulate the cell cycle. Integrins are also involved in the attachment of cells to each other and to the extracellular matrix, the part of a tissue that is not part of any cell.

Research by Juliano’s lab has shown that integrins regulate key signaling pathways, especially those involving mitogen-activated protein kinases, which are enzymes that regulate cellular activities such as gene expression, mitosis, differentiation, and apoptosis.

The second major area of Juliano’s research, and the one that he currently focuses on, is macromolecular therapeutics.

“Basically we are devising ways to get large-molecule therapeutic agents into the right site in the body,” he says. “That has gone in a lot of different directions over the years.”

Juliano was involved in some of the earliest work using liposomes to deliver therapeutic agents of infectious diseases and cancer. He worked on the development of some of the liposomal products that are currently on the market. One of those was Abelcet, a liposomal form of amphotericin B that is used to treat system fungal infections.

“Usually these are only used in very seriously ill patients, people who have HIV or are undergoing chemotherapy and then acquire a systemic fungal infection, which can be very dangerous in those individuals,” Juliano says. “Basically, liposomal amphotericin B is an improved form of amphotericin B because it’s less toxic and therefore can be dosed at higher levels.”

Juliano’s current work in macromolecular therapeutics looks at ways to deliver potentially therapeutic antisense oligonucleotides—short segments of RNA and DNA that can bind to specific strands of messenger RNA and prevent protein translation. His lab is looking for ways to use antisense oligonucleotides to inhibit messenger RNA from cancer-related genes. To do so, he is making chemical conjugates of the oligonucleotides with ligands that target specific receptors on the cell surface. Juliano says that technique allows for enhanced uptake and altered inter-cellular distribution. It also makes it possible to target specific cell types by targeting receptors specific to each cell type.

“Different receptors are expressed in different cells, so potentially you can perhaps target your oligonucleotides to lung cells but not liver cells, or heart cells but not kidney cells, depending on their display of receptors,” he says.

Juliano’s lab is working on three families of receptors to see how well they can target different groups of receptors. One of those families, G-protein coupled receptors, is the largest family of receptors.

“There are about eight hundred GPCRs, so there are a lot of opportunities there for selective targeting,” Juliano says.

Carolina Center of Cancer Nanotechnology Excellence

Juliano is the principal investigator on a National Cancer Institute grant for the Carolina Center of Cancer Nanotechnology Excellence. The grant is worth about $3 million a year in direct cost and is part of an NCI initiative to explore using nanotechnology in cancer research and treatment.

“Several years ago, the National Cancer Institute decided that nanotechnology might have important applications toward cancer research, diagnosis, and treatment, and they decided to establish a program in that area,” Juliano says. “It’s called the Alliance for Nanotechnology in Cancer. Essentially that program has funded a number of smaller grants and also has funded eight large centers around the country, and UNC was lucky enough to be one of those centers.”

The center at UNC brings physical scientists in chemistry, computer, science, and biomedical engineering together with tumor biologists and oncologists to apply their technology to cancer research.

Juliano points to work by Joe DeSimone, PhD, and Otto Zhou, PhD, as examples of the center’s success. DeSimone, the William R. Kenan Jr. Distinguished Professor of Chemistry and Chemical Engineering, developed a versatile and flexible method for creating and harvesting shape-specific nanobiomaterials that have the same molecular mass. The method, Particle Replication In Non-wetting Templates (PRINT), is delicate and general enough to be compatible with various important next-generation agents for cancer therapy, detection, and imaging. PRINT particles are now being designed to help research in cancer prevention, diagnosis and treatment.

Zhou, the Lyle Jones Professor of Physics and Materials, developed nanotube X-ray devices that make it possible to conduct X-ray imaging that is faster, requires lower dose, and is more sensitive.

“Both of those technologies have attracted a lot of attention and have led the creation of spin-off companies that are involved in commercializing those products,” Juliano says.

“The center has been very successful. It has gotten a lot of people in physical sciences interested in and working on biomedical problems. It’s been quite productive in terms of publications and patents. It’s been quite exciting.”