The Nebraska Center for Rapid Bioanalysis

• An Overview of the UNMC current COBRE centers and Nanoimaging core facility

Yuri Lyubchenko COBRE Retreat - January 16, 2009

Nebraska Center for Cellular Signaling

PI: Peggy Wheelock, Ph.D.

First COBRE grant was received in 2003.

This CoBRE grant was to establish a center for cellular signaling that will function to bring together senior investigators to serve as mentors for junior investigators. Five junior investigator projects are funded on this grant and the goal was to assist these investigators in securing independent funding for their work.

Nebraska Center for Cellular Signaling PI: Peggy Wheelock, Ph.D.

July 2008: NIH renews Dr. Wheelock's CoBRE grant

• the winning formula Peggy Wheelock - to have two high profile researchers as mentors for five years. • seven junior investigators at UNMC obtained their own RO1 grants from the National Institutes of Health (NIH). •This success has led to the NIH approving a renewal of Dr. Wheelock's Centers of Biomedical Research Excellence (CoBRE) grant for another five years at $10.9 million. Peggy Wheelock: The grant has allowed us to bring together

outstanding junior and senior faculty with similar interests, which greatly enhances the science knowledge and opportunities for collaboration."

Nebraska Center for Nanomedicine

• Dr. Kabanov, the Parke-Davis Chair in Pharmaceutics, UNMC College of Pharmacy, is the director of the Nebraska Center for Nanomedicine • Funding - $10.6 M • "

This grant allows us to attract the best and brightest scientists to Nebraska, to develop novel technologies that could contribute to the economy of the state with the help of spin-off companies that would bring the results of the scientific research to public use

," Dr. Kabanov said.

Nebraska Center for Nanomedicine

• Nanomedicine defines the emerging area of science that uses nanomaterials, small polymeric particles to deliver drugs safely to disease sites, such as cancer tumors.

Center of Drug Deliver and Nanomedicine (CDDN)

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This regent-approved Center was established to support an interdisciplinary team of scientists with specific expertise in nanomedicine, drug delivery, therapeutics, and diagnostics. Nanomedicine is a medical intervention at the molecular scale for curing disease or repairing damaged tissue.

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Nebraska Center for Nanomedicine

The four projects currently being supported through the COBRE funding are as follows.

Project 1: Principal investigator:

Elena V. Batrakova, Ph.D., assistant professor of pharmaceutical sciences.

Mentor:

Howard Gendelman, M.D., chairman, department of pharmacology and experimental neuroscience, director, Center for Neurovirology and Neurodegenerative Disorders.

Dr. Batrakova's project focuses on creating a drug delivery system to treat Parkinson's disease using nanozymes and immune cells in the brain as the delivery agent. Nanozymes are tiny particles consisting of an enzyme in a protective polymer coat.

Project 2: Principal investigator:

Matthew Zimmerman, Ph.D., assistant professor of cellular and integrative physiology.

Mentor:

Irving Zucker, Ph.D., professor and chairman of the cellular and integrative physiology department. Dr. Zimmerman's research project focuses on using antioxidant therapy and nanozymes to treat hypertension.

Project 3: Principal investigator:

Huanyu Dou, Ph.D., assistant professor, department of pharmacology and experimental neuroscience.

Mentor:

Surinder Batra, Ph.D., professor in the department of biochemistry and molecular biology. Dr. Dou's research project focuses on developing a cell-based nanoformulated anti-tumor therapy that would improve biodistribution of the drug to the tumor and reduce chemotherapy-induced neurotoxicity.

Project 4: Principal investigator:

Joseph Vetro, Ph.D., assistant professor, Center for Drug Delivery and Nanomedicine, department of pharmaceutical sciences.

Mentor:

Alexander Kabanov, Ph.D., director, Nebraska Center for Nanomedicine. Dr. Vetro's research focuses on inhibiting the growth of cancer tumors by using specially developed nanocarrierse that disrupt the tumor's ability to recruit surrounding blood vessels.

UNMC Shared Resources/Core Facilities

http://www.unmc.edu/dept/vcr/index.cfm?L1_ID=26&CONREF=18 Mass Spectrometry and Proteomics Core Facility Nanoimaging Core Facility

Nanoimaging Core Facility

The facility is equipped with three instruments: • The combination state of the art AFM microscope (Asylum Research Veeco, Santa Brabara, CA) mounted on an inverted fluorescence microscope (Olympus), allowing simultaneous detection of fluorescently labeled samples, high resolution AFM imaging, force spectroscopy, and manipulation at the nanoscale. • The stand-alone AFM (MM AFM, Veeco, Santa Brabara, CA), capable of high-resolution imaging of various biological samples in air and aqueous solution. •AFM force robot (JPK Germany) allowing automate acqusition of the data on the intermolecular interactions various molecular systems •The facility provides expertise for researchers in imaging, force spectroscopy analysis, elasticity measurements and other applications of Atomic Force Microscopy

AFM-optical microscope

MM AFM microscope

MM AFM microscope

JPK Force Robot

Force Spectrosope Head Stable base frame with active vibration isolation Force Spectroscope Base Controller with TCP/IP-Interface User PC with ForceRobot Software

Nebraska Center for Cellular Signaling PI: Peggy Wheelock, Ph.D.

July 2008: NIH renews Dr. Wheelock's CoBRE grant

• the winning formula Peggy Wheelock - to have two high profile researchers as mentors for five years. • seven junior investigators at UNMC obtained their own RO1 grants from the National Institutes of Health (NIH). •This success has led to the NIH approving a renewal of Dr. Wheelock's Centers of Biomedical Research Excellence (CoBRE) grant for another five years at $10.9 million. http://www.unmc.edu/dentistry/wiki/NCCS.htm

http://app1.unmc.edu/publicaffairs/todaysite/sitefiles/today_full.cfm?match= 4656 http://www.unmc.edu/dentistry/wiki/Dr%20Margaret%20J%20Wheelock.htm

UNMC: New Potential projects

LC-MS Determination of Bile Acid-Sulfates As Biomarkers for Liver Function

Yazen Alnouti, Ph.D

Assistant Professor Department of Pharmaceutical Sciences University of Nebraska Medical Center

BA Enterohepatic Recirculation

95% Under normal conditions, BAs are contained within the enteroheaptic system, spill over into blood is minimum, and urinary excretion is negligible

Rapid detection of drugs for protein misfolding diseases.

Alexey Krasnoslobodtsev, Department of Pharmaceutical Sciences, University of Nebraska Medical Center COBRE 16 January, 2009

Natively folded conformations of various types Conformational prerequisites for amyloidosis Partially folded intermediate Misfold 1 Misfold 2 Misfold 3

Center for Pharmaceutical Biophysics

• The research outcomes of the Center will serve as the basis for the discovery of diagnostic agents and new pharmaceutical entities for the prevention, treatment and/or cure of diseases. • The Center’s mission is to unite efforts of researchers working in the areas of basic and applied pharmaceutical and biomedical sciences, chemistry, biochemistry, and engineering who are exploring and developing new technologies for the analysis of biological nanosystems in such biopharmaceutical science fields as high throughput screening of drugs, drug development, diagnostics, therapeutics, single molecule imaging/tracking and biomarker assays.