The events leading to the development of cancer often involve a series of sequential molecular derailments. The complexities of these derailments are frequently specific not only to the type of cancer, but can also be specific to an individual tumor. However, despite these challenges, investigations characterizing the global or universal aberrations seen in human cancers have provided many effective therapeutic strategies to the combat human malignancies. The current dissertation focuses on two neglected areas of study in the cancer biology field, the study of lncRNA isoform-specific alterations and the post-translational modifications of the critically important MYC oncoprotein in cancer.

In the beginning chapters of this dissertation, we explore isoform-specific alterations in a subtype of renal cell carcinomas, known as clear cell renal cell carcinoma (ccRCC). ccRCC is one of the most prevalent cancers within the United States, and can be particularly difficult to treat with conventional therapies. As such, new therapeutics strategies are needed to treat ccRCC in its later stages of the disease. ccRCC has been shown to have severe aberrant RNA production and processing, lending itself as a prime candidate to explore isoform-specific alterations. Furthermore, using new computational methods, we identified previously uncharacterized events of differential transcript and usage in ccRCC implicating several novel genes in the pathology. Discovered within these transcriptomic analyses was a long non-coding RNA, referred to as HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1), which was found to be specifically downregulated in ccRCC and regulates key genes involved in the hypoxia pathway. In chapter 3, we investigate HOTAIRM1 further examining its function in ccRCC and its role in kidney cell differentiation and maintenance.

In the last two chapters, we discuss and evaluate the effects of two disparate levels of MYC regulation. First, we discuss the complex nature of the interplay between MYC expression and numerous lncRNAs, in what is referred to as the lncRNA-MYC network. In this review, we reveal the breadth of the complexities of how MYC is regulated by lncRNAs and how MYC regulates its oncogenic function through the use of lncRNAs. Finally, with the development of innovative transgenic cell lines, expressing different mutant forms of MYC, we demonstrate that different acetylation states of MYC can have gene-selective effects and consequently alter different molecular pathways.

Ecological observatories are a new class of multiuser research infrastructure designed and deployed to address a broad range of continental-scale ecological questions that until only recently were not technologically feasible. These highly networked ecological observatories, spread across the United States and featuring a diverse integration of programmable sensing capabilities and remote observational functions are expected to enable a transformation in the scope of environmental research, particularly in relation to understanding how global climate shifts and local and regional land use changes will quantitatively affect the composition, structure, and dynamics of the nation’s ecosystems and services. Observing systems research focused on terrestrial ecology is one of four core research application fields of the Center for Embedded Networked Sensing, which operates an engineering and experimental test bed located at the James San Jacinto Mountains Reserve, a biological field station that is part of the University of California Natural Reserve System. This paper describes the various experimental and deployed embedded networked sensing systems at the James Reserve, and suggests how similar systems and related infrastructure will be key to meeting the engineering and science objectives of future ecological research.

This paper describes a novel experiment in which two very different methods of underwater robot localization are compared. The first method is based on a geometric approach in which a mobile node moves within a field of static nodes, and all nodes are capable of estimating the range to their neighbours acoustically. The second method uses visual odometry, from stereo cameras, by integrating scaled optical flow. The fundamental algorithmic principles of each localization technique is described. We also present experimental results comparing acoustic localization with GPS for surface operation, and a comparison of acoustic and visual methods for underwater operation.