Research Summary

Our laboratory is focused on using mass spectrometry-based proteomics to discover new biology and therapeutic targets in hematologic malignancies (blood cancers) and genetic disease. Our major hypothesis is that "biology happens at the protein level" – i.e. RNA-level analysis is not enough. This is particularly true when investigating biological signatures driven by protein post-translational modifications, protein-protein interactions, and altered sub-cellular localization.

To achieve these goals, our inter-disciplinary group aims to integrate proteomics-based screening with "multi-omics" bioinformatics, clinical data, epigenetic methods, genome engineering, antibody engineering, cellular engineering, chemical biology, and mechanistic biology. In particular, significant efforts in the lab are focused on developing new proteomics methods to discover cell surface targets, and then utilize emerging protein and cellular engineering approaches to develop novel cancer immunotherapies to eliminate disease. Furthermore, my group includes the UCSF Stephen and Nancy Grand Multiple Myeloma Translational Initiative Laboratory. In this role, we collaborate with industry and academic partners to advance preclinical evaluation of novel myeloma therapeutics using a suite of in vitro and in vivo approaches.

Research Funding

  • August 3, 2021 - July 31, 2023 - ClinTAD: A Tool for Improving Clinical CNV Interpretation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R03HD105804
  • July 1, 2021 - June 30, 2023 - Structural Surfaceomics: A Strategy for Immunotherapy Target Discovery , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA263229
  • March 1, 2018 - February 28, 2023 - Exploiting myeloma proteome remodeling to extend proteasome inhibitor efficacy , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA226851
  • September 30, 2016 - May 31, 2021 - In vivo monitoring of oxidative protein folding through time-resolved quantitative mass spectrometry , Principal Investigator . Sponsor: NIH, Sponsor Award ID: DP2GM123500

Education

2002, Princeton University, Princeton, NJ, A.B., Chemistry
2008, Columbia University, New York, NY, Ph.D, Neurobiology/Biophysics
2009, Columbia University, New York, NY, M.D., Medicine
2012, University of California, San Francisco, CA, Residency, Laboratory Medicine
2014, University of California, San Francisco, CA, Post-Doc, Pharmaceutical Chemistry

Honors & Awards

  • 2008
    Winner, Wharton Venture Award, team “Bayesian Diagnosis Pro”, U. Penn.
  • 2008
    Dean's Award for Excellence in Research, Columbia U. College of P&S (best Ph.D. thesis prize)
  • 2010, 2013
    Paul Strandjord Young Investigator Award, Academy of Clinical & Lab. Physicians and Scientists
  • 2010
    Laurence J. Marton Award for Excellence in Research, Dept. Lab. Med., UCSF
  • 2010
    Julius Krevans Award for Clinical Excellence, San Francisco General Hospital/UCSF
  • 2012
    NIH Ruth F. Kirschstein F32 Post-doctoral Fellowship (declined)
  • 2012
    Jane Coffin Childs Fund Post-doctoral Fellowship (declined)
  • 2012-15
    Damon Runyon Cancer Research Foundation Post-doctoral Fellowship
  • 2015
    Dale Frey Breakthrough Award, Damon Runyon Cancer Research Foundation
  • 2016
    Doris Duke Charitable Foundation Clinical Scientist Development Award
  • 2016
    NIH New Innovator Award
  • 2017
    Janet Rowley Memorial Award, Gabrielle's Angels Foundation for Cancer Research

Selected Publications

  1. Huang HH, Ferguson ID, Thornton AM, Bastola P, Lam C, Lin YT, Choudhry P, Mariano MC, Marcoulis MD, Teo CF, Malato J, Phojanakong PJ, Martin TG 3rd, Wolf JL, Wong SW, Shah N, Hann B, Brooks AN, Wiita AP. Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma. Nat Commun. 2020 Apr 22;11(1):1931.
    View on PubMed
  2. Leidal AM, Huang HH, Marsh T, Solvik T, Zhang D, Ye J, Kai F, Goldsmith J, Liu JY, Huang YH, Monkkonen T, Vlahakis A, Huang EJ, Goodarzi H, Yu L, Wiita AP, Debnath J. The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles. Nat Cell Biol. 2020 Feb;22(2):187-199.
    View on PubMed
  3. Choudhry P, Mariano MC, Geng H, Martin TG 3rd, Wolf JL, Wong SW, Shah N, Wiita AP. DNA methyltransferase inhibitors upregulate CD38 protein expression and enhance daratumumab efficacy in multiple myeloma. Leukemia. 2020 Mar;34(3):938-941.
    View on PubMed
  4. Sarin V, Yu K, Ferguson ID, Gugliemini O, Nix MA, Hann B, Sirota M, Wiita AP. Evaluating the efficacy of multiple myeloma cell lines as models for patient tumors via transcriptomic correlation analysis. Leukemia. 2020 Oct;34(10):2754-2765. Epub 2020 Mar 2.
    View on PubMed
  5. Liu TY, Huang HH, Wheeler D, Xu Y, Wells JA, Song YS, Wiita AP. Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics. Cell Syst. 2017 Jun 28;4(6):636-644.e9.
    View on PubMed

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