Arun Wiita, MD, PhD

Director, UCSF Stephen and Nancy Grand Multiple Myeloma Translational Initiative Laboratory
Assistant Director, UCSF Clinical Cytogenetics Laboratory
Assistant Professor
Department of Laboratory Medicine
+1 415 514-6238

In cancer research, significant effort has been devoted to understanding how changes in DNA can be harnessed to develop new diagnostic and therapeutic strategies.  However, changes in DNA must be decoded into changes in proteins to actually lead to alterations of cellular phenotype.  How aberrations in the cancer genome broadly relate to changes in the cancer proteome, and thus to disease pathogenesis, remain much less well-characterized.  Furthermore, changes in the cancer proteome play a critical role in determining cancer response to therapy, whether through cell death, adaptation, or resistance.  

To bridge this gap between cellular genotype and phenotype, our group focuses on the use of high-throughput technologies, including unbiased and targeted mass spectrometry-based proteomics, ribosome profiling, and mRNA-seq, to study the consequences of genomic and therapeutic perturbation in cancer.  We pair these technologies with generating new cancer models through CRISPR/Cas9 genome engineering to evaluate the proteomic impacts of specific, clinically-relevant genomic alterations.  We also use quantitative modeling to describe the dynamic interplay between transcriptional changes and protein-level dynamics in cancer cells.

Our group primarily studies these problems in the context of hematologic malignancies (blood cancers).  In particular, most projects in the lab focus on multiple myeloma, the second-most common hematologic malignancy in the U.S., with >25,000 cases diagnosed per year.  This malignancy of plasma cells currently has no known cure.  Our group is also the home of the UCSF Stephen and Nancy Grand Multiple Myeloma Translational Initiative Laboratory. In this capacity, we perform preclinical evaluation of novel therapeutics and diagnostics for this disease, in collaboration with partners both at UCSF and in industry.

Overall, our ultimate goal is to use a combination of systems-level knowledge and biological validation to develop new approaches to extend survival in myeloma and other hematologic malignancies.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
None
Research Summary: 
We are interested in understanding the complex links between alterations in the genome and therapeutic perturbation in driving changes in cellular phenotype at the level of the proteome.

Websites

Publications: 

The p97 inhibitor CB-5083 is a unique disrupter of protein homeostasis in models of Multiple Myeloma.

Molecular cancer therapeutics

Le Moigne R, Aftab BT, Djakovic S, Dhimolea E, Valle E, Murnane M, King EM, Soriano F, Menon MK, Wu ZY, Wong ST, Lee GJ, Yao B, Wiita AP, Lam C, Rice J, Wang J, Chesi M, Bergsagel PL, Kraus M, Driessen C, Kiss von Soly S, Yakes FM, Wustrow D, Shawver L, Zhou HJ, Martin TG, Wolf JL, Mitsiades CS, Anderson DJ, Rolfe M

Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics.

Cell systems

Liu TY, Huang HH, Wheeler D, Xu Y, Wells JA, Song YS, Wiita AP

Antibody-drug conjugate targeting CD46 eliminates multiple myeloma cells.

The Journal of clinical investigation

Sherbenou DW, Aftab BT, Su Y, Behrens CR, Wiita A, Logan AC, Acosta-Alvear D, Hann BC, Walter P, Shuman MA, Wu X, Atkinson JP, Wolf JL, Martin TG, Liu B