The family of proprotein convertases has been recently implicated in tumorigenesis and metastasis in animal models. However, these studies have not yet been completely corroborated in human tumors. Here, we show that mRNA, protein expression, and protein cleavage profiles of proprotein convertases 1 and 2 are altered in liver colorectal metastasis, compared to unaffected and normal liver. Active PC1 is overexpressed in tumor, correlating with its mRNA profile. Moreover, the enhanced PC2 processing pattern in tumor correlates with the overexpression of its specific chaperone 7B2, which in turn may represent a target for early diagnosis and treatment. The increased PC2 maturation, as well as the overexpression and altered processing of PC1 may be either a cause or a consequence for the observed metastasic phenotype. Nevertheless, they may result in the alteration of the secretory pathway, which could therefore, modify the cellular microenvironment and thus favor tumor growth and/or metastasis.

Thesis (Ph.D.)--University of California, San Francisco, 2005. / Source: Dissertation Abstracts International, Volume: 66-12, Section: B, page: 6537. Adviser: Frank McCormick.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007. / Source: Dissertation Abstracts International, Volume: 68-06, Section: B, page: 3699. Adviser: John W. Erdman. Includes bibliographical references (leaves 115-136) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--University of California, San Francisco, 2006. / Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2370. Adviser: Donald E. Ganem.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007. / Source: Dissertation Abstracts International, Volume: 68-07, Section: B, page: 4374. Adviser: Edward J. Roy. Includes bibliographical references (leaves 124-148) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6703. Adviser: Matthew A. Wallig. Includes bibliographical references (leaves 65-110) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph. D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6770. Adviser: Paul Hergenrother. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--University of California, San Francisco, 2008. / Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5319. Adviser: Marylin J. Dodd.

Thesis (Ph. D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6806. Adviser: John Katzenellenbogen. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

Although techniques in molecular imaging have advanced considerably over the past several decades, there remain numerous categories of biological molecular targets that are refractory to straightforward imaging. Among these is molecular oxygen, which is vital to a host of physiological as well as pathological processes, as well as the amorphous pigment pheomelanin, which may play a formerly unappreciated role in melanoma carcinogenesis. This thesis describes two related bodies of work that advance techniques in oxygen and pheomelanin imaging, respectively. First, inspired by a desire to understand how hypoxia affects cancer chemotherapy on a cellular level, we designed and synthesized a novel oxygen-sensitive, dendritic nanoconstruct that is capable of spontaneously penetrating through hundreds of microns of multiple cellular layers. After demonstrating our nanoconjugate's oxygen sensitivity using time-domain phosphorescence lifetime measurements, we demonstrate that it retains its oxygen sensitivity in a 3D spheroid in vitro model of ovarian cancer through the use of a custom-made, near infrared-optimized confocal phosphorescence imaging system. Drawing from this approach, we then describe the fabrication and calibration of a separate oxygen-sensing bandage platform for use in wound-healing applications, and demonstrate its use in ex vivo and in vivo animal systems. The second body of work describes the use of non-linear four-wave mixing techniques to facilitate straightforward imaging of the molecular pigment pheomelanin. Recent findings suggest that pheomelanin may play a previously unappreciated role in melanoma carcinogenesis, even in the complete absence of an ultraviolet light insult. However, due to its pale color, pheomelanin is difficult to visualize against a skin background, making its study challenging. After constructing a femtosecond-pulsed coherent anti-Stokes Raman scatter (CARS) microscopy imaging system, we use imaging and spectroscopy to provide proof-of-concept that pheomelanin can be imaged through a combination of CARS microscopy and electronically-enhanced four-wave mixing. We then use our non-linear imaging system to specifically observe pheomelanin in isolated "redhead" mouse melanocytes, and show through an siRNA gene knock-down strategy that our system can be used to observe changes in pheomelanin signal upon modification of biological pathways known to affect pheomelanin synthesis.