University of California, Riverside

Department of Chemistry



Faculty


 

 

Kathryn Uhrich
Professor of Chemistry & CNAS Dean

 

B.S. 1986, University of North Dakota (Grand Forks, ND)
Ph.D. 1992, Cornell University (Ithaca, NY)
Postdoctoral Research Fellow 1992, Bell Laboratories
Postdoctoral Research Fellow 1993-95, MIT

Office: 2258D Geology
Phone O/L: (951) 827-3101
Email: kathryn.uhrich@ucr.edu
Research Area: Materials Chemistry, Organic Chemistry


Research Summary

The UGroup laboratory centers on polymeric bioactives; specifically, the design of biocompatible, biodegradable polymers that can improve human health. Given that our starting materials are naturally occurring and our polymeric bioactives safe, we incorporate green chemistry approaches to the polymer life-cycle. We engage motivated and creative researchers from chemistry, engineering, biology and pharmacy at all levels - from high school students to visiting scientists from international labs. This diverse and creative research environment leads to many discoveries; we learn the vocabulary of intellectual property (e.g., patents) and industrial collaborations as it pertains to our published research in bioactive delivery.

Bioactive Polymers: Amphiphilic Macromolecules

Amphiphilic macromolecules (Ams) are essentially polymeric micelles that were first designed as  nano carriers to water-solubilize hydrophobic drug molecules. Yet, in the past few years, we've discovered that the AMs themselves are bioactive and are valuable additives for lipid-based delivery systems. We demonstrated that these systems enhance delivery of anticancer drugs and effectively deliver siRNA into cancer cells. The dramatic change was our observation that AMs control cellular uptake of LDL and inhibit athero-inflammation. We now design anti-atherogenic polymers that target macrophage receptors and mitigate low-density lipoprotein (LDL) uptake.

Regarding bioactivity, the Ams specifically inhibit the uptake of "bad cholesterol" (i.e., LDL). In collaboration with Prabhas Moghe (Rutgers, Biomedical Engineering), we examine methods to enhance biological interactions - evaluating amphiphilicity, branching, stereochemistry, pKa and other factors via new chemical structures. With funding from NIH and the Coulter Foundation, we are developing new bioactive polymers that can potential reverse atherogenesis.

With their ability to quickly migrate into the nucleus, we continue to optimize the AMs for delivery of genes (i.e., siRNA) and anticancer agents. In one approach with Charlie Roth (Rutgers, Biomedical Engineering), we include cationic elements - namely ethyleneimine - within the AM structure to promote siRNA complexation. In another approach with Evan Mintzer (Stern College, Chemistry), we embed AMs with lipids to create AM-lipid complexes (i.e., lipopolyplexes) to promote delivery of water-insoluble drugs as well as siRNA.

Another critical aspect in developing novel technologies is stability - stability upon storage/sterilization and stability in vivo. With Bob Prud'homme (Princeton, Chemical Engineering), the AMs are kinetically entrapped into nanoparticles via flash precipitation such that AMs are stabilized in serum over extended time periods.

Polymers from Bioactives: PolyActives

 PolyAspirin is the first example of a PolymerDrug: a polymer that degrades into a bioactive such as salicylic acid that can locally reduce inflammation and pain. In addition to non-steroidal anti-inflammatory drugs (NSAIDs), many other drug classes have been investigated, including antiseptics, antioxidants, antimicrobials, and opiates.

For example, by chemically incorporating morphine into a polymer (i.e., PolyMorphine), we created a new composition that may alleviate tolerance development of opiates. In our collaboration with Lei Yu (Rutgers, Genetics), we invented a polymer that extends pain relief from hours (as with injectable morphine) to days.

With funding from NIH, we are developing NSAID-based polymers that locally deliver salicylic acid to promote bone regeneration. In our collaboration with Pat O'Connor (Rutgers, Orthopedics), PolyAspirin suppresses inflammation, enabling bone formation. With Dana Graves (UPenn, Periodontics), we've demonstrated significant bone regeneration in diabetic animals with PolyAspirin-containing bone allograft material.

In a related project, we explore novel hydrogels that incorporate NSAIDs and/or antioxidants for wound care and personal care. With Luiz Catalani (Uni Sao Paulo, Chemistry), stable hydrogels are fabricated by admixing NSAIDS that release over days (rather than hours).

Currently, we are exploring polymers that incorporate bioactives of interest to our industrial partners (e.g., Chanel). With Polymer Therapeutics (PRx), we are developing the PolyAspirin technology into wound care devices, such as sutures.

Awards

Selected Publications

 

More Information 

General Campus Information

University of California, Riverside
900 University Ave.
Riverside, CA 92521
Tel: (951) 827-1012

Department Information

Department of Chemistry
Chemical Sciences
501 Big Springs Road

Tel: (951) 827-3789 (Chair's Assistant)
Fax: (951) 827-2435 (confidential)
E-mail: jingsong.zhang@ucr.edu

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