Alberto Rascon
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Mail code: 1604Campus: Tempe
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Alberto Rascón joins the School of Molecular Sciences from San José State University as an associate professor where his research program focused specifically on Aedes aegypti mosquito midgut proteases. During his tenure at SJSU, Rascón was involved as a mentor in the CSU Louis Stokes Alliance for Minority Participation (CSU‐LSAMP) program, the National Institutes of Health Maximizing Access to Research Careers (MARC) program, and the NIH Research Initiative for Scientific Enhancement (RISE) program, also serving as a co‐coordinator for seven years. Before departing SJSU, Rascón helped in establishing the new U*RISE (T34) training program as co-PI to ensure continued training of URM students in the biomedical sciences. Rascón is a first-generation URM student, earning a bachelor's degree in chemistry from California State University, Bakersfield (2002), and a doctorate in biochemistry from the University of Arizona (under the supervision of Dr. Roger L. Miesfeld), where he first worked on the Ae. aegypti mosquito. After his graduate studies, Rascón joined the lab of Dr. James H. McKerrow as an NIH Institutional Research and Academic Career Development Award (IRACDA) Scholar focusing on enzymes from human parasitic worms and proteases from human amoeba parasites. Currently, the overarching goal of his research is to delineate the biological functions and physiological substrates of Ae. aegypti proteases involved in midgut bloodmeal protein digestion, salivary gland tissues, and eggshell melanization, as well as determine viral pathogen-host protease interactions in the mosquito.
- NIH/NIGMS IRACDA Postdoctoral Scholar, University of California, San Francisco 2011-2013
- Ph.D. Biochemistry, University of Arizona, 2010
- B.S. Chemistry, California State University, Bakersfield, 2002
Proteases play essential roles in many important biological processes. Specifically, in the Aedes aegypti mosquito, proteases are important in the midgut (for blood meal protein digestion), the salivary gland (possible enhancement in viral infectivity and dissemination), and for egg/embryo survival (eggshell formation and melanization). However, the exact roles of Ae. aegypti proteases in these processes are either limited or still relatively unknown, which reveal vulnerabilities that can be exploited to attenuate transmission of human viral pathogens. Full understanding of protease function is needed for the development of novel vector control strategies and to better understand viral pathogen/host protease interactions. The work in the Rascón lab lies at the interface of both Chemistry and mosquito Biology, especially in the development of small molecule mosquito-specific inhibitors.
1) Determine the Function of ‘Orphan’ Midgut Proteases in the Blood Meal Digestion Process. At SJSU, the initial focus was on the four most abundant midgut proteases, which revealed the importance of three late phase proteases on fecundity (AaSPVI, AaSPVII, AaLT). However, no synergistic effect was observed when all three late phase proteases were knocked down at once. No other midgut proteases had been identified until 2010, when five new serine proteases (AaSPI-AaSPV) were discovered. These ‘orphan’ proteases lack targets and functions as they have yet to be characterized in vivo or in vitro. Additionally, two chymotrypsin-like enzymes (AaCHYMO and AaJHA15) have been identified and have been minimally studied in vitro, but again their exact role in digesting blood meal proteins are relatively unknown. Therefore, work has recently expanded to focus on the newly identified serine proteases (AaSPI-AaSPV) and the two chymotrypsin-like proteases.
2) Determine the Role of Midgut and Salivary Gland Proteases in Viral Pathogen Enhancement/Disruption. An uninfected Ae. aegypti mosquito becomes a vector upon imbibing a viremic blood meal. In the first 1-2 days after infection, the viruses invade the midgut epithelial cells through endocytosis, and replication is initiated thereafter. After ~3 days post infection, the viruses spread from the midgut, then throughout the mosquito body, ending in the salivary glands, with maximal viral titers observed 12-18 days post infection. Interestingly, work focusing on Dengue virus serotype 2 (DENV-2) in Ae. aegypti in vivo, resulted in a decrease in midgut DENV-2 RNA copies when feeding mosquitoes an infectious blood meal in the presence of a soybean trypsin inhibitor (STI). However, gene expression studies of Ae. aegypti non-infected and infected (DENV-2) mosquitoes revealed the downregulation of AaET in infected mosquitoes, indicating a possible immune role against the virus, and providing evidence that midgut proteases may be playing an immune role against DENV-2. However, more work needs to be conducted to conclusively state this. No other research labs have followed up on this idea. In addition, changes in salivary gland protease gene expression were observed to be up-regulated when the mosquito is infected with the DENV-2 serotype. Two main questions arise: Do these proteases aid in viral replication? Or are these salivary gland proteases involved in liquefying dermal tissues by specifically digesting the extracellular matrix components, enhancing infectivity and dissemination in the human host. The answer to these questions may lead to a new inhibitor target and affect viral pathogen transmission.
3) Determine the Role of Proteases in Eggshell Formation and Melanization. The Ae. aegypti mosquito lays her eggs in an aquatic environment, which allows water to freely pass through the transparent eggshell, but after two hours the eggshell darkens via melanization. The melanized eggshell serves as a protective layer for embryonic development, as well as preventing egg shrinkage caused by desiccation. Although the melanization process and the different protein types involved in this process are known, the role of proteases in the Ae. aegypti mosquito melanization process is not. Affecting the protective layer needed for embryonic development could serve as a new and different vector control strategy.
Simington, C.J., Oscherwitz, M.E., Peterson, A.J., Rascón, A.A., Jr., Massani, B.B., Miesfeld, R.L., and Isoe, J. (2020) Characterization of essential eggshell proteins from Aedes aegypti mosquitoes. bioRxiv. https://doi.org/10.1101/2020.04.06.027706.
Isoe, J., Koch, L.E., Isoe, Y.E., Rascón, A.A., Jr., Brown, H.E., Massani, B.B., and Miesfeld, R.L. (2019) Identification and characterization of the mosquito-specific eggshell organizing factor from Aedes aegypti mosquitoes. PLoS Biol. 17(1): e3000068.
Nguyen, J.T., Fong, J., Fong, D., Fong, T., Lucero, R.M., Gallimore, J.M., Burata, O.E., Parungao, K.A. and Rascón, A.A. Jr.* (2018) Soluble Expression of Recombinant Midgut Zymogen (Native Propeptide) Proteases from the Aedes aegypti Mosquito Utilizing E. coli as a Host. BMC Biochem.19(1). *Corresponding Author.
Long, T., Rojo-Arreola, L., Shi, D., El-Sakkary, N., Jarnigan, K., Rock, F., Mewan, M., Rascón, A.A., Jr., Lin, L., Cunningham, K.A., Lemieux, G.A., Podust, L., Abagyan, R., Ashrafi, K., McKerrow, J.H., and Caffrey, C.R. (2017) Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target. PLoS Negl. Trop. Dis. 11(7): e0005680.
Bulman, C.A., Bidlow, C.M., Lustigman, S., Cho-Ngwa, F., Williams, D., Rascón, A.A., Jr., Tricoche, N., Samje, M., Bell, A., Suzuki, B., Lim, K.C., Rojo-Arreola, L., Supakorndej, N., Supakorndej, P., Wolfe, A., Chen, S., Wilson, C., Ang, K.H., Arkin, M., Franklin, C., Marcellino, C, McKerrow, J.H., Debnath, A., and Sakanari, J. (2015) FDA-Approved Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis. PLoS Negl. Trop. Dis. 9(2): e0003534.
Rascón, A.A., Jr.* and McKerrow, J.H. (2013) Synthetic and Natural Protease Inhibitors Provide Insights Into Parasite Development, Virulence, and Pathogenesis. Curr. Med. Chem. 20(25), 3078-3102. *Corresponding Author.
Rascón, A.A., Jr., Gearin, J.J., Isoe, J., and Miesfeld, R.L. (2011) In vitro Activation and Enzyme Kinetic Analysis of Recombinant Midgut Serine Proteases From the Dengue Vector Mosquito Aedes aegypti. BMC Biochem. 12:43.
Isoe, J., Rascón, A.A., Jr., Kunz, S., and Miesfeld, R.L. (2009) Molecular Genetic Analysis of Midgut Serine Proteases in Aedes aegypti Mosquitoes. Insect Biochem. Mol. Biol. 39(12), 903-912.
Courses
2024 Fall
Course Number | Course Title |
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BCH 392 | Intro to Research Techniques |
BCH 492 | Honors Directed Study |
BCH 493 | Honors Thesis |
CHM 392 | Intro to Research Techniques |
CHM 492 | Honors Directed Study |
CHM 493 | Honors Thesis |
BCH 392 | Intro to Research Techniques |
CHM 392 | Intro to Research Techniques |