"A New Genesis": The "Silent Vigil" at Duke University, April 5th-12th, 1968

Honors thesis

Engineering a BCR-ABL-activated caspase for the selective elimination of leukemic cells.

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of caspase activation and tyrosine kinase/adaptor protein signaling to forge a unique approach for selectively killing leukemic cells through the forcible induction of apoptosis. We have engineered caspase variants that can directly be activated in response to BCR-ABL. Because we harness, rather than inhibit, the activity of leukemogenic kinases to kill transformed cells, this approach selectively eliminates leukemic cells regardless of drug-resistant mutations.

Impact of the Interdecadal Pacific Oscillation on Tropical Cyclone Activity in the North Atlantic and Eastern North Pacific.

Tropical cyclones (TCs) are among the most devastating weather systems affecting the United States and Central America (USCA). Here we show that the Interdecadal Pacific Oscillation (IPO) strongly modulates TC activity over the North Atlantic (NA) and eastern North Pacific (eNP). During positive IPO phases, less (more) TCs were observed over NA (eNP), likely due to the presence of stronger (weaker) vertical wind shear and the resulting changes in genesis potential. Furthermore, TCs over NA tend to keep their tracks more eastward and recurve at lower latitudes during positive IPO phases. Such variations are largely determined by changes in steering flow instead of changes in genesis locations. Over the eNP, smaller track variations are observed at different IPO phases with stable, westward movements of TCs prevailing. These findings have substantial implications for understanding decadal to inter-decadal fluctuations in the risk of TC landfalls along USCA coasts.