Ben Major, Ph.D.

Alan A. and Edith L. Wolff Professor
Cell Biology and Physiology
Otolaryngology

Cancer Biology Program
Biochemistry, Biophysics, and Structural Biology Program
Biomedical Informatics and Data Science Program
Molecular Cell Biology Program

  • 314-273-3675

  • 402 McDonnell Sciences Bldg.

  • bmajor@wustl.edu

  • http://majorlab.wustl.edu/

  • proteomics, functional genomics, lung cancer, signal transduction, WNT, oxidative stress

  • Studying how perturbation of specific signal transduction pathways contributes to the initiation, progression and dissemination of cancer

Research Abstract:

My lab studies how perturbation of specific signal transduction pathways contributes to the initiation, progression and dissemination of cancer. We employ a systems level integrative discovery platform to characterize pathway dynamics in normal and disease cell models. More specifically, we use mass spectrometry-based proteomics to define the protein-protein interaction and protein proximity networks, along with phosphorylation and ubiquitylation post-translational modifications. Much of our effort focuses on the WNT and NRF2/oxidative stress signaling pathway. We then annotate the nodes within the networks for function, as determined by established and novel functional genomic screening technologies. Integration of these data with disease-associated mutation and gene expression data yields a powerful tool for discovery-a disease annotated physical/functional map. Critical to our success is the development and implementation of computational scoring algorithms, relational database construction and data visualization. Ultimately, the models and hypotheses produced are challenged through mechanistic studies employing cultured cancer cells, new and established mouse models, clinical tissue and various biochemical, molecular biology, structural and cell biological systems. 


KEAP1/NRF2 oxidative and metabolic stress response pathway in lung cancer, head and neck cancer and esophageal cancer. Basic mechanisms, biochemistry, proteomics, drug screens, mouse models, clinical trials. 

WNT signaling pathway. Basic mechanisms, biochemistry, proteomics, time resolved protein-protein interactions. 

Understudied kinases altered in human disease. Protein-protein interaction and proximity networks. Imaging. Crispr-A and Crispr-I genetic screens. ORF screens. Phosphoproteomics. 

Proteomics. Phospho- and ubiquitylation proteomics. Kinase enrichment mass spectrometry. Multiplex quantitative mass spectrometry. Proteoinformatics. Data acquisition algorithm development. 


Mentorship and Commitment to Diversity Statement:

The diverse approach we take to deciphering signaling pathways provides a rich learning environment for students and postdoctoral scientists. In addition to standard biochemical, cell biological and molecular biology approaches, scientists in my lab are running loss-of-function genetic screens, CRISPR and ORF-based gain-of-function screens, chemical discovery, and an array of quantitative mass spectrometry experiments. They are also learning and developing new computational approaches for data integration, analysis and hypothesis generation. 

Since 2009, I have mentored 12 PhD graduate students and 2 computer science MS students (6 completed their PhDs; 2 completed MS degree) and 15 postdoctoral scientists. I served as the Associate Director of the UNC Cancer Cell Biology Training Program T32 (pre-doc) and have mentored two HHMI Gilliam Fellows. In 2019, I was given an award for Excellence in Basic Science Mentoring from the University of North Carolina. I also led a First Year Group class to incoming graduate students within the UNC BBSP graduate umbrella program. My class of ~15 students met 1.5 hours per week for the academic year where I taught scientific presentation, scientific writing, ethics and overall how to succeed in graduate school. I also co-designed and taught a graduate-level course on data reproducibility and rigor. I participated in and then led faculty mentorship and inclusive excellence workshops at UNC-Chapel Hill and for the HHMI Gilliam program. In July of 2019, I moved my lab to Washington University in St. Louis to continue my research program and mentorship, and to establish a new Center for Mass Spectrometry and Systems Medicine.

We are a team of academic scientists. The scientific discoveries we make and cures and knowledge we seek rests solely on the happiness, enthusiasm, skill, and rigor of our team members. We embrace diversity of thought and people, continually striving for maximal inclusive excellence. This diversity has and continues to empower our discovery and our science. Our mission is two-fold: to discover the inner-workings of the diseased cell to reveal new therapies and cures, and to teach, train and support members of our scientific team en route to their next career stage. In many ways, my responsibility and my privilege is to do all that I can to help and guide my students and postdocs get to where they want to go. Often, the next career stage is not known in the beginning, to which I offer advice and my experiences as guidance. Once it takes shape, I tailor my mentorship, resources and guidance to suit the needs of my mentee, which includes advocating, networking, and training along the career arc. I believe mentorship is a lifelong commitment.

For my students and post-docs, we work together to develop and revisit mentorship compacts, which includes alignment of expectations and formal training plans. I meet with all students at least once a week in a 1:1 setting. My mentorship plan rests on the following guiding principles. 

a. Developing wisdom in project selection and constant re-evaluation.  We encourage everyone within our respective laboratories to remain up-to-date with emerging scientific discoveries, leveraging both the literature and local and national meetings. They are expected to take this information, their previous training, and their creativity to synthesize research proposals addressing important biological and medical questions. Through our weekly meetings, we fine-tune these ideas into testable hypotheses and then into a shortlist of experiments aimed as quick and conclusive validation. As the project progresses, our meetings and conversations invariably progress to decisions of importance and novelty, as not all projects are equally worthy of pursuit. 

b. Employment of emerging technologies.  In many ways, scientific success rests on the timely inclusion of emerging technologies. Members of our laboratories are expected to embrace emerging technologies, often playing important role in technological invention as well. Mastering all facets of protein mass spectrometry, functional genomic and chemical screens, cell biology and imaging, and biochemistry, enzymology and signal transduction makes for an attractive toolset as our students and postdoc move to their next career stage. Equally important is that these approaches enable unbiased, quantitative and rigorous study and discovery of human disease.

c. Telling a complete story.  The ‘Omics”-based discovery platform employed by the Major laboratory provides a powerful Figure #1 for manuscripts and grants.  It does not, however, provide conclusive mechanism or disease relevance.  Scientists within our laboratories pursue the complete story, employing all available experimental approaches to that end.

d. Transitioning to independence.  As scientists progress further into their project(s) and careers, they will assume an increasing responsibility for handling tasks associated with running an academic laboratory or industry team: scientific writing and presentation, teaching/mentorship, collaborations, and lab finances.

Selected Publications:

Brittany M. Bowman et. al., A Conditional Mouse Expressing an Activating Mutation in the NRF2 Displays Hyperplasia of the Upper Gastrointestinal Tract and Decreased White Adipose Tissue. Journal of Pathology Oct;252(2):125-137. 2020. 

Megan J. Agajanian et. al., AAK1 inhibits WNT signaling by promoting clathrin-mediated endocytosis of LRP6. Cell Reports, 2019 Jan 2;26(1):79-93. 

Cloer EW, et. al., p62-Dependent Phase Separation of Patient-Derived KEAP1 Mutations and NRF2. Molecular and Cellular Biology, 2018. Aug 20. pii: MCB.00644-17. 

Babita Madan et. al., The USP6 Oncogene Promotes Wnt Signaling by Deubiquitylating Frizzleds. Proceedings of the National Academy of Sciences, 2016. May 9th. 

Matthew P. Walker et. al., FOXP1 Potentiates Wnt/b-catenin Signaling in Diffuse Large B-cell Lymphoma. Science Signaling. 2015 Feb. 3rd 

Emily M Cousins et. al., Competitive Kinase Enrichment Proteomics Reveals that Abemaciclib Inhibits GSK3b and Activates WNT Signaling. Molecular Cancer Research. 2017 Nov 13th. 

Hast BE et. al., Proteomic analysis of ubiquitin ligase KEAP1 reveals associated proteins that inhibit NRF2 ubiquitination. Cancer Research, Apr 1st, 2013;73(7):2199-210. 

Goldfarb, Dennis, et. al., Approximating isotope distributions of biomolecule fragments. American Chemical Society Omega. 2018. 

Dennis Goldfarb et. al., Spotlite: An Improved Algorithm and Web Application for Predicting Co-Complexed Proteins from Affinity Purification – Mass Spectrometry Data. Journal of Proteome Research, 2014 Oct 10th 

Siesser PF et al., FAM123A Binds Microtubules and Inhibits the Guanine Nucleotide Exchange Factor ARHGEF2 to Decrease Actomyosin Contractility. Science Signaling. 2012 Sep 4; 240(5):ra64

Last Updated: 4/17/2021 4:43:57 PM

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