Current Fellow Spotlight
Jordan Pritts, a Ph.D. Candidate at the University of Maryland, Baltimore, and Dr. Sarah Michel, are researching the Influenza Virus. Pritts is starting the second year of his AFPE Pre-Doctoral Fellowship.
Jordan writes: “Annual influenza outbreaks have various detrimental effects to our community each year, including loss of work due to sick time, hospitalizations, and even death. In addition to seasonal outbreaks, there have been pandemics in the past of highly virulent strains that lead to high mortality and morbidity rates. Investing in research aimed at defending the human population against the flu is crucial to public health. New strains are becoming more and more resistant to the current therapies, so it is crucial that we develop new and improved therapeutics. This research proposal aims to lead the groundwork on characterizing one of influenza’s main virulence pathways as well as to identify drug leads and possible FDA approved drugs that can be repurposed as anti-influenza therapies. A new anti-influenza drug has the ability to provide defenses for populations that cannot be vaccinated, ameliorate seasonal flu symptoms, act as a first-line defense against pandemic outbreaks, or as a prophylactic treatment for high-risk populations.”
Regarding his research so far, he explains: “To date, I isolated full-length CPSF30 for the first time and identified a 2Fe-2S cofactor in addition to five zinc finger sites. I demonstrated that the protein binds to specific pre-mRNA targets: the AAUAAA polyadenylation sequence (PAS) and Uracil-rich RNA through its CCCH and CCHC zinc finger domains respectively. I teased out the role of the domains and RNA sequence and identified a competitive binding mechanism. Additionally, the 5 CCCH zinc finger domains of CPSF30 are sensitive to mutations within the PAS and can be completely abolished by some single and double mutations within the hexamer. Some of these single mutations can be related to different diseases with changes in this hexamer. These data suggest that CPSF30 as well as its RNA target have highly specific interactions that drive the overall polyadenylation machinery’s activity. These results set the stage for current efforts focused on the interaction of NS1A with CPSF30/RNA and future efforts to identify inhibitors.”
AFPE Gateway Awardee Rachel Carley, a Pharm.D. candidate at the University of Rhode Island, recently spent six weeks in a research lab at the FDA’s Office of Biotechnologies. She writes:
“I had the unique experience of being a part of one the FDA’s research labs and was able to participate in the Summer Intern Poster Session. This lab had a different primary focus them my home laboratory but still utilized similar techniques. This lab focused on development of monoclonal antibody drugs and I was able to learn the production, purification and analytical process that goes into producing a monoclonal antibody. I spent most of my time in the analytical lab answering questions pertaining to after market problems of drugs, like aggregation and temperature fluctuations of biologic drug products. We used an IgG1 model antibody to perform freeze/thaw and aggregation studies, followed by buffer formulation studies. We utilized techniques like UPLC-SEC, DLS and CD to characterize the impact of thermal stressing on the antibody. In a very short amount of time we were able to produce enough data to present two posters at the FDA Summer Poster Session. These types of studies are important for everyday use of these types of drug. Especially if they deviate from the package insert to determine if these conditions are safe for drugs to be given to patients if any of these conditions arise.”
Regarding her mentored research at the University of Rhode Island, she writes:
“In my lab with my mentor Dr. Cho, we are currently working on a project to determine the binding potential of Perfluorinated Alkyl Substances (PFASs) to transthyretin, the thyroid carrier hormone. This is important because epidemiological studies suggest that PFASs are endocrine disruptors without any data to prove their binding potential. We hope to elucidate the binding potential of this class of molecules to transthyretin to determine their endocrine disruption potential. If PFASs bind strongly to transthyretin and can displace thyroxine, T4, the natural thyroid hormone and ligand for transthyretin, then PFASs can contribute to endocrine disorders like hypothyroidism. We plan to test these properties with a powerful, cutting edge technique, Surface Plasmon Resonance, SPR. SPR can calculate the association and dissociation rates of molecules to determine a number of kinetic properties, like Kd and Ka. By better understanding the binding potential of these molecules we can better understand their impact in the human body. “
Rachel was also the recipient of the University of Rhode Island’s 2019 University of Rhode Island Undergraduate Research and Scholarship Excellence Award in the Life Sciences, Physical Sciences, and Engineering.
AFPE Pre-Doctoral Fellow, Larry Rodriguez, is a student at the University of Southern California. Alongside his mentor, Dr. Daryl Davies, Larry Rodriguez is researching “The Role of P2X4 Receptors within the Mesolimbic Pathway in Dopamine Signaling and Disease.” In the video below, Rodriguez explains his research in greater detail.Larry Rodriguez – Suppressing receptor function in the brain ex vivo using CRISPR/CAS from USC School of Pharmacy on Vimeo.
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