Research

This section is dedicated to my research experiences as an undergraduate at Hiram college and as a research assistant at The Ohio State University comprehensive cancer center.

Preclinical efficacy for a novel tyrosine kinase inhibitor, ArQule 531 against acute myeloid leukemia

ArQule-531 is a potent multikinase inhibitor that has previously shown success in in-vitro Chronic Lymphocytic Leukemia (CLL) models. Given its multi-target profile, we evaluated its efficacy in pre-clinical in-vitro and in-vivo AML models. My research findings demonstrated a significant survival advantage in an aggressive AML mouse model. Furthermore, we pursued successful drug combination experiments and were able to show both in-vitro and in-vivo synergy between ArQule-531 and Venetoclax (a potent BCL-2 inhibitor).

Broad-spectrum inhibitors like ArQule 531, provide an efficient way of targeting multiple proteins in a heterogeneous disease like AML. Targeting multiple proteins also limits the chance of resistance caused by a compensatory increase in expression of other oncogenic proteins. Furthermore, administering ARQ 531 as a combination therapy, can help target additional pathways and thereby reduce the chance of relapsed disease.

Elgamal, O.A., Mehmood, A., Jeon, J.Y. et al. Preclinical efficacy for a novel tyrosine kinase inhibitor, ArQule 531 against acute myeloid leukemia. J Hematol Oncol 13, 8 (2020).

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Understanding AML Biology

Using Mass-Cytometry, we are investigating the difference in immune cell repertoire between wild type mice and mice with an AML phenotype. This immunophenotyping research will benefit the leukemia research community by providing data on a spontaneous mouse-models closely resembling leukemia in patients. Upon determining the specific antigens that differentiate AML tumor cells from normal cells, we can manipulate the immune cells of diseased mice to fight leukemia.

Waterfowl Water Management

The Hiram College Field Station is home to White Winged Wood Ducks (WWWDs), an endangered waterfowl species housed as part of a captive breeding program with the Akron Zoo. The WWWD population has undergone rapid decline and literature suggests that one of the causes is avian tuberculosis caused by Mycobacterium avium. The presence of this pathogen and its natural aquatic reservoir hosts, free-living amoeba, are of obvious concern to our captive breeding program.

As a means to clean the water for the WWWD enclosures, Hiram College employs the use of plant-based biological filters. My undergraduate research focused on studying the efficacy of these filters by testing the water pre- and post-filtering for the presence of overall microbial load as well as specific organisms, namely Mycobacterium avium, other members of the genus Mycobacterium, and several genera of free-living amoeba.

We hypothesized that the presence of microbes should decrease after the water had passed through the biological filters. We also expected to see no Mycobacterium avium present in the pond water. My lab protocols utilized standard lab microbial cultivation techniques and DNA detection via semi-quantitative PCR.

Our PCR results showed the presence of Mycobacterium spp. and free-living amoeba, but no detectable M. avium. The latter negative result cannot be confirmed due to the absence of positive control and the fact that our lab-designed M. avium primers had never been tested previously. Luckily, researchers at the Sylvan Heights Bird Park in North Carolina do have access to a true positive control and have agreed to collaborate with us. We await confirmation from them about the functionality of our primers and their limit of detection. This information would help us conclude whether ducks at the field station are truly safe from the pathogen and whether other primer sets should be used for future experimentation.

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