The basic research laboratory of Mark J. Federspiel, Ph.D., is currently focused on understanding the basic mechanistic details of how enveloped viruses enter cells.
Most of his studies use avian sarcoma and leukosis viruses (ASLV), a group of retroviruses that serve as a powerful experimental model system. Ongoing projects seek to define the critical determinants in both the viral glycoprotein and the cellular receptors required for efficient virus entry.
Dr. Federspiel and his team employ a combination of molecular, genetic, biochemical and structural experimental approaches to dissect this complex interaction, from the initial binding through the stages of viral and cellular membrane fusion. They have also begun structural characterization of the viral glycoproteins and their interactions with their receptors in their native form on virions using cryo-electron tomography.
Dr. Federspiel also directs the Viral Vector Production Laboratory, a resource established to enable Mayo Clinic investigators to translate promising virus-based therapies to human clinical trials. The laboratory develops large-scale virus production and purification procedures required for translating what were once laboratory reagents for use in humans.
The Viral Vector Production Laboratory operates a good manufacturing practices (GMP) facility on the Mayo Clinic campus in Rochester, Minn., for the production of viral products for phase I and II clinical trials. The Viral Vector Production Laboratory has enabled the translation of six different research projects to testing in patients in phase I clinical trials.
Dr. Federspiel's laboratory
Focus areas of Dr. Federspiel's basic research laboratory are:
- Determining how viruses can evolve to use a new cell protein as a receptor
- Determining structures of the viral glycoproteins and cellular receptors required for efficient virus entry
- Determining the different conformational changes in the viral glycoproteins required to achieve fusion of the viral and cell membranes to deliver a subviral particle
- Exploiting the ASLV-based vector system to efficiently express and display a wide variety of foreign proteins on the viral surface to optimize binding properties (for example, single-chain antibodies)
Viral Vector Production Laboratory
In the Viral Vector Production Laboratory, the major projects so far have been developing new cancer therapeutics. Specifically, these use oncolytic viruses, including measles virus and vesicular stomatitis virus, to kill cancer cells and generate a unique immune response.
Specific disease areas include:
- Ovarian cancer
- Multiple myeloma
- Prostate cancer
- Brain cancer
- Liver cancer
Significance to patient care
An improved understanding of virus entry will allow the development of new therapies to block this critical step in infection.
The Viral Vector Production Laboratory provides the expertise to translate virus-based therapeutic research at Mayo Clinic to testing in patients in clinical trials.