Creating more effective and safer drugs with reduced side effects

Tiny, chemically-engineered drug particles are powerful elements that can either treat or threaten the conditions in your body. Especially for patients with a chronic pain or disease, the issue of effective and safe medication becomes much more critical and precautionary. In an ideal world, drugs would have no side effects, treat problems as they are designed to, and keep other healthy areas of the body safe. Dr. Carston Wagner, Professor & Endowed Chair of Medicinal Chemistry at the University of Minnesota, therefore researches ways to develop more effective and safer drugs, or therapeutics. By using a range of different techniques and disciplines that are not traditionally put together in chemistry, Dr. Wagner hopes to produce medicine with reduced side effects and increased performance.

Dr. Wagner and his team’s research has already had a major impact on the development of new antiviral and anticancer drugs, such as the anti-HCV drug, Sovaldi. This research has in turn opened doors for them to create a new target for the treatment of chronic pain and drug addictions. Applying their insights from working at the interface of chemistry and biology, Dr. Wagner and his team have also been able to engineer immune cells with molecular  “GPS devices”. The modified patient immune cells are then enabled to seek and destroy cancer cells. Dr. Wagner hopes to expand the futue of this multipurpose technology to tissue regeneration and vaccine development. Ultimately, the goal of Dr. Wagner’s laboratory is to apply the principles of chemical biology and medicinal chemistry to design new chemical and cell-based therapies that will address difficult to treat diseases.

Current research areas include:

  • Applying chemical induced dimerization to guide the self-assembly of protein nanorings: Dr. Wagner and his team have combined their expertise from chemical biology and technology to construct protein-based nanoparticles that are biodegradable to use as a targeting element that can hit specific cells as intended. By further advancing this technology, Dr. Wagner hopes to better facilitate drug delivery, tumor imaging and the targeting of immune and stem cells for tumor targeting or tissue regeneration.
  • Designing therapeutic nucleotide prodrugs that can also be targeted and activated by diseased tissues: The fundamental research on the development of methods has allowed Dr. Wagner and his lab to prepare nucleotides to be delivered as drug molecules. The building blocks of nucleic acids that make up the DNA or RNA, the nucleotides are used to make genetic coding and sequencing. Creating a set of nucleotide codes to look for cancer genetic codes and designing ways to deliver nucleotides as drugs that are selective and nontoxic then enable researchers to develop antiviral, anticancer drugs that are activated by diseased tissues while keeping other healthy tissues safe. This method is unconventional but proven to be successful by its performance in Sovaldi. By studying how these new kinds of compounds can be activated and released into cells, Dr. Wagner hopes to apply it to treating cancer.
  • Uncovering the natural function of Hint proteins and applying relevant knowledge to the design of anticancer, antiviral drugs, and new pain medications: Understanding nucleotide therapeutics has further led Dr. Wagner and his team to discover other radical ways to use nucleosides for pain medications as well as for treating addiction. For example, they have discovered that certain proteins are referred to as the Hint proteins, and these proteins involved in activating antiviral drugs are also involved in mechanisms that can control pain - namely the neuropathic pain and tolerance to opiate pain medications. Developing molecules to target these Hint proteins, the team has found that when the Hint molecules or enzymes are hit, they can substantially reduce pain and restore sensitivity to opiate pain medications, making pain medications useful again. In the future, using this information, Dr. Wagner hopes to develop more effective medications for pain and addiction with fewer side-effects.

Bio

Dr. Carston Wagner has always loved to figure things out and to think outside the box. During college he realized that one had to know chemistry in order to be able to impact the future of biological research. Both his graduate research and later his postdoctoral studies thus allowed him to explore the interface of chemistry and biology, and he began to see how to best apply his knowledge to the development of new medicines. Over the last 20+ years, he has been fortunate to be able to follow his own path of discovery with the goal of applying the new scientific knowledge for the treatment of cancer, viral diseases, pain and addiction. “It is a great job!” he says.

In college, Dr. Wagner was a long-distance runner and a marathoner. Although he no longer runs marathons, he remains a long-distance runner. Running has strengthened his character and his values that bleed into his research, where he has learned that persistence is key in the face of obstacles and setbacks. The physical and mental health that running provides him reminds him to always keep moving and not to dwell on the setbacks, and to push forward in the midst of difficult circumstances.

He is also very dedicated to training the next generation of young scientists, and has been involved in graduate education as the Director of Graduate Education for almost a decade. Education has always been a part of his vision, as well as having practical impact on the patients who will reap tremendous benefits from his research. Dr. Wagner tackles every research question with patients in mind, approaching every problem with the perspective of impacting human health. With one eye on discovery and another in building applications, Dr. Wagner hopes to make a tangible difference in the lives of humanity.

For more information, visit his website at: http://www.medicinal-chemistry.org/wagner/wagner-research-group

Awards

Fellow, American Association for the Advancement of Science, 2012

Excellence in Graduate Education Faculty Award, 2012

University of Minnesota, College of Pharmacy

3M University Relations Award, 2002

Teacher of the Semester, Pharm.D. II, Fall 1999

N.I.H. First Award, 1993

Patents

U.S. Patent No. 6,475,985: "Nucleosides with Antiviral and Anticancer Activity"

Issued 11/05/02

U.S. Patent No. 6,881,747 B2: "Small Molecules for Inhibition of Function and Drug Delivery to Leukocytes"

Issued 4/19/05

U.S. Patent No. 7217523: "Nucleoside Phosphoramidates and Nucleoside Phosphoramidases"

Issued 5/15/07

U.S. Patent No. 8236925: "Protein Nanorings"

Issued 8/07/12

U.S. Patent No. 8815830 B2: "Nucleosides with antiviral and anticancer activity"

Issued 06/15/06