• 6031
    Citations
20042024

Research activity per year

If you made any changes in Pure these will be visible here soon.

Personal profile

Research interests

We study how perturbation of specific signal transduction pathways contributes to human disease. We employ a "systems level" integrative discovery platform to characterize pathway dynamics in normal and disease model systems. Specifically, we use protein mass spectrometry to define the protein-protein interaction/proximity networks and phosphorylation modification for the WNT and NRF2/oxidative stress signaling pathways. We then annotate the nodes within the network for function, as determined by established and novel functional genomic screening technologies. Integration of these data with disease-associated data gene expression 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, mouse models, clinical tissue and various biochemical and cell biological systems. We are recruiting enthusiastic scientists into the following general research fields:

1. KEAP1/NRF2 oxidative stress response pathway in lung cancer, head and neck cancer, esophageal cancer and Parkinson’s Disease. Basic mechanisms, biochemistry, proteomics, drug screens, mouse models, a new clinical trial.

2. WNT signaling pathway in pancreas cancer and lung cancer. Basic mechanisms, biochemistry, proteomics, time resolved protein-protein interactions.

3. Understudied kinases altered in human disease. Protein-protein interaction and proximity networks. ORF screens. Phosphoproteomics.

4. Mass spectrometry-based proteomics. Phospho- and ubiquitylation proteomics. SureQuant clinical proteomics. Proteoinformatics. Data acquisition algorithm development. 

Mentoring

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.

Clinical interests

We study signal transduction pathways that are altered in a number of human diseases, including lung and upper-airway cancers and neurodegeneration. Clinically, our research is most developed in head and neck squamous cell carcinoma (HNSCC). We have developed new clinical proteomic technologies to quantify the proteome in archived FFPE tumor blocks. Coupling these data with therapy and patient outcomes is revealing novel biomarkers. We have also opened our first clinical trial which is testing a the pyrimethamine drug as an inhibitor of the NRF2 pathway in HNSCC. Multiple clinical research projects and training opportunities are available for our students and postdocs. 

Education activities and interests

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, viral-based gain-of-function screens, 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 23 undergraduate students, 15 PhD graduate students and 2 computer science MS students (6 completed their PhDs; 3 completed MS degree) and 14 postdoctoral scientists. Currently, I mentor 3 postdoctoral scientists, 3 pre-doctoral students, 1 senior staff scientist and 2 junior faculty. Prior to coming to WashU, I served as the Associate Director of the UNC Cancer Cell Biology Training Program T32 (pre-doc), and as mentor for two HHMI Gilliam Fellows. I also led a First Year Group class to incoming graduate students within the UNC BBSP graduate umbrella program where I taught scientific presentation, writing, RCR-ethics and overall how to excel in graduate school. In 2018, I received an award for Excellence in Basic Science Mentoring from the UNC School of Medicine. Also at UNC, I co-designed and taught a graduate-level course on data reproducibility and rigor. I participated in faculty mentorship courses at UNC-Chapel Hill and for the HHMI Gilliam program, having recently presented to HHMI leadership on inclusive excellence mentorship of graduate students from underrepresented groups. In July of 2019, I moved my lab to Washington University in St. Louis to continue my research program and student mentorship, and to establish the WashU Mass Spectrometry Technology Access Center (MTAC). 

Available to Mentor:

  • PhD/MSTP Students

Fingerprint

Dive into the research topics where Ben Major is active. These topic labels come from the works of this person. Together they form a unique fingerprint.
  • 1 Similar Profiles

Collaborations and top research areas from the last five years

Recent external collaboration on country/territory level. Dive into details by clicking on the dots or