Welcome to the UCSF Wiita Lab!

We are an experimental research group in the Dept. of Laboratory Medicine at the University of California, San Francisco. Our lab is focused on how changes in the level of proteome govern cellular phenotype, and how these proteomic changes can be targeted for new therapeutic strategies. We approach this problem both from the perspective of blood cancer as well as constitutional genetics.

Over the past two decades our knowledge of genomic changes in disease states has greatly expanded. However, any true change in cellular or disease phenotype must be decoded from genomic changes into changes in the proteome, whether at the level of protein abundance, post-translational modification, or protein localization. Understanding and quantifying this decoding of the genome to proteome on a broad scale remains much less understood. To bridge this gap, we employ mass spectrometry-based proteomics as a core technology to motivate downstream mechanistic and therapeutic investigation.

For our studies in blood cancers, for example, we aim to link specific tumor genotypes to aberrant signalinga at the level of the proteome. We also aim to monitor complex effects of drug- and genome-level perturbation using a combination of global proteome analysis by shotgun mass spectrometry, targeted mass spectrometry methods, chemical enrichment of cell-surface localized and DNA-bound proteins, RNA-seq, and ribosome profiling. We are particularly interested in transcriptional regulation by epigenetic modulation, translational regulation at the level of the ribosome, and trafficking of cell-surface proteins in relationship to cancer immunotherapy. One of our major goals is to develop new proteomic technologies, based on chemical biology strategies, to advance these investigations. 

In constitutional genetics, we are particularly interested in DNA copy number variants (CNVs), known to cause effects such as cardiac anomalies, autism, and developmental delay. Yet patients with these CNVs can manifest very different phenotypes. We aim to understand whether this "variable penetrance" may result from patient-specific alterations at the level of the proteome.

Our group is also the home of the UCSF Stephen and Nancy Grand Multiple Myeloma Translational Initative Laboratory. In this capacity, we aim to push forward the development and validation of new therapeutic strategies in multiple myeloma, a currently incurable malignancy of plasma cells and the second most common hematologic malignancy in the United States. We are particularly excited about developing new immunotherapy strategies for this disease with the aim of moving new treatments to the clinic. Our ultimate goal is to use a combination of systems-level knowledge and biological validation to develop novel therapeutic and diagnostic approaches to extend survival in myeloma and other hematologic malignancies.