Mark Farrell

Mark Farrell
Assistant Professor, Department of Medicinal Chemistry
University of Kansas

 

 

Targeting viral sweet spots with Lectin mediated immunotherapy (2018-19)

Viral associated diseases have many detrimental effects on human health, however, a broad acting antiviral agent that could quell viral outbreaks has yet to be developed. One major difficulty impeding the development of such a therapeutic is the identification of a common targetable motif. While the structures of viral envelope glycoproteins vary vastly from virus to virus, the glycans that decorate the envelope
glycoproteins, represent a potential common targeting motif. Lectins, such as Cyanovirin-N, and Griffithsin, have been shown to neutralize an array of viruses via their interactions with glycans present on viral envelope glycoproteins. To date, their use as microbicides has been widely investigated, although other potential applications are also under investigation.

In this project we propose to prepare Cyanovirin-N, and Griffithsin constructs that can act as broadly acting antiviral immunotherapeutic. These molecules would maintain the ability to specifically bind viral high-mannose glycans, while having the added functionality of being able to recruit the immune system to destroy viral particles, and glycoprotein expressing viral infected host cells in a species and strain independent manner.

The inhibition of polysialytransferase ST8Sia II: A novel approach toward the prevention of cancer metastasis (2017-18)

The prevention, inhibition and reversal of cancer metastasis is of upmost importance in order to improve the state of standard of care for cancer patients.The deadliest aspect of cancer is its ability to metastasize – migrate from a primary tumor to multiple distant sites. This is often the final, lethal step in the progression of solid tumors. To metastasize, a tumor cell has to learn to survive independently, enter the blood stream, travel to and recognize a potential new home, leave the blood stream, establish itself in a new setting, invade nearby tissues and attract its own blood supply to allow growth. Although a distinct, complicated, multi-step physiological process with its own dynamics, metastasis has remained largely unexplored and thus poorly understood.

Importantly, each step in this complicated process provides a therapeutic target. This project will investigate the ability of peptide derived small molecules to inhibit the posttranslational polysialylation of the neuronal cell adhesion molecule (NCAM), a glycoprotein which plays a key role in the detachment of cancerous metastatic cell from the primary site of tumorigenesis. In the absence of the polymeric polysialic acid cells expressing NCAM lack the ability to metastasize. Specifically these compounds will be designed to block a key interaction between NCAM and the polysialyltransferase ST8SiaII, which is essential for efficient polysialylation.