Thomas Graeber, Ph.D.,

Thomas Graeber, Ph.D. 

Professor, Molecular and Medical Pharmacology; Director, UCLA Metabolomics Center

Bio

Thomas Graeber, Ph.D., takes an interdisciplinary ‘systems biology’ approach that merges biology, chemistry, mathematics and computation/bioinformatics to understand how cancer cells communicate with their environments, process nutrients and evade therapies. Graeber gathers multiple types of large data sets from patient tumor samples and then applies computational approaches to find trends, such as how tumor cells metabolize nutrients differently from other cells. The ultimate goal of this work is to identify new ways to diagnose and treat cancer on a cellular, patient-specific level.

Graeber aims to make advances in understudied cancers with few or no available targeted therapies. Rather than focusing on how cancer affects one specific organ, such as the prostate or lungs, Graeber looks for commonalities among different cancer types in order to identify vulnerabilities that can be targeted by new drugs or cellular therapies. He is currently collaborating with clinician scientists to identify the common genetic activities that enable aggressive, treatment-resistant cancers from different tissues to metastasize.

Another area of focus in Graeber’s lab is determining how cancer cells de-differentiate, or revert back to an earlier stage of development. De-differentiation can also be linked to cancer stem cells, which are able to self-renew and give rise to all cell types found in a tumor. De-differentiated cells can evade common treatments such as chemotherapy and radiation and cause recurrence of the disease. Graeber discovered that melanomas – cancers that arise from the cells that produce pigments – can be divided into four distinct subtypes according to their stages of differentiation or maturity. Graeber then found that less-mature melanoma cells showed sensitivity to a self-inflicted cell death called ferroptosis. This led to the finding that certain subtypes of melanoma could be targeted by a combination of existing cancer therapies and ferroptosis-inducing drugs.

An additional novel therapeutic avenue Graeber investigates is how to turn genetic and chromosomal flaws found across aggressive cancer types into a vulnerability rather than a strength. The genomes of aggressive cancers have a great deal of abnormalities. Unfortunately, cancer cells can adapt their metabolism and other cell processes to use genomic instability as an advantage to fuel their rapid growth. Graeber is working to identify the mechanisms that enable these cells to function despite their flawed genomes in order to develop drugs to stop this process and make cancer’s genetic instability a fatal flaw.

Graeber earned a doctorate degree in physics and cancer biology from Stanford University and completed post-doctoral fellowships in signal transduction and computational biology at UCLA.

Publications

Honors & Affiliations

Honors

  • Giants of Science Passion Award, American Cancer Society, 2017

Affiliations

  • UCLA Crump Institute for Molecular Imaging
  • Nanotechnology Program, UCLA Jonsson Comprehensive Cancer Center
  • UCLA California NanoSystems Institute

Funding

Graeber’s work is funded by the W.M. Keck Foundation, the National Institutes of Health, the UCLA Specialized Program of Research Excellence (SPORE) in Prostate Cancer, a Metabolism Theme Award from the UCLA David Geffen School of Medicine, the UCLA Clinical and Translational Science Institute and the UCLA Broad Stem Cell Research Center, including support from David B. Katzin, the Hal Gaba Director’s Fund for Cancer Stem Cell Research and the Binder Foundation.