Florian Muller, Ph.D.
Cancer Systems Imaging
Areas of Research
- Targeted Therapy Research
Muller's team is working to develop a small-molecule Enolase inhibitor for in vivo proof-of-principal, and ultimately, as a clinical candidate for the treatment of cancers which harbor deletions of ENO1. Their goal is to demonstrate the universality of the collateral lethality approach and expand the utility to other passenger deleted genes. The team is using genomic deletions to gain insight into the basic biochemistry and metabolism of human cancer, as well as to utilize this knowledge for imaging purposes.
Florian Muller, Ph.D. pioneered a novel strategy for molecular targeted therapy in cancer, exploiting vulnerabilities exposed by passenger deleted genes, an approach known as “collateral lethality”. Muller presented proof-of-principal data for one example of this strategy, where glioma cells with passenger deletion of the glycolytic enzyme, ENO1 are selectively sensitive to inhibition to its redundant homologue, ENO2. Since then, his team has explored chemical matter as a basis for generating a clinical candidate Enolase inhibitor to treat cancers with homozygous ENO1 deletions. During this work, they discovered that a natural product antibiotic of unknown mode of action termed SF2312, is a highly potent, nM-affinity inhibitor of Enolase and demonstrated that SF2312 shows strong selective toxicity towards ENO1-deleted glioma cells. They then carried out structure-activity relation studies that led to the synthesis of a molecule termed HEX. HEX is a potent competitive inhibitor of the Enolase enzyme and 4 to 10 times more effective against ENO2 than ENO1. However, both SF2312 and HEX are negatively charged phosphonate inhibitors with limited cell permeability. To improve permeability and efficacy the team is investigating various pro-drugging approaches. The most advanced Enolase inhibitor so far, POMHEX, is a pivoxyl esters of HEX which shows strong selective toxicity against ENO1-deleted glioma cells in vitro and displays anti-neoplastic activity in pre-clinical intracranial orthotopic tumor models.
Florian Muller, Ph.D. is an Assistant Professor in the Department of Cancer Systems Imaging at The University of Texas, M.D. Anderson Cancer Center. He received his Ph.D. in Cell and Structural Biology from The University of Texas Health Science Center at San Antonio.
Read more about Dr. Muller here.
Principal Investigator, 2.4 months, Institutional Start-up Research Funding, The University of Texas MD Anderson Cancer Center, 10/30/2014-10/2/2019, $750,000 ($150,000/year)
Principal Investigator, 2.4 months, Passenger Deletion of ENO1 as a Targetable Vulnerability in Cancer,
RSG-15-145-01-CDD, American Cancer Society (ACS), 1/1/2016-12/31/2019, $765,000 ($165,000/year)
Co-Principal Investigator, 0.12 months, In Vivo Molecular Breast Imaging with TC 99M Sestamibi for the Prediction of
Multidrug Resistance in Triple Negative Breast Cancers, CABI/GE In-Kind Research Grant, CABI/GE IN-KIND Research Grant, Multi-Investigator Imaging (M12) Research Award, PI - Rauch, 4/1/2016-3/31/2021, $264,392
Principal Investigator, 0.12 months, Rising STARS Award (Muller), The University of Texas MD Anderson Cancer Center, 12/1/2016-11/30/2019, $250,000
Principal Investigator, 2.4 months, Collateral Lethality mediated tumor eradication by T-cell activation, Andrew Sabin Family
Foundation Fellows Award, 4/1/2018-3/31/2020, $100,000 ($50,000/year)
Principal Investigator, 3 months, Collateral Deletions Expose Targetable Metabolic Vulnerabilities in the PTEN locus, 1-R21-CA226301-01, NIH/NCI, 4/6/2018-3/31/2020, $239,250 ($130,500/year)
Project Leader, 20%, The Transformative Glioblastoma Initiative, Brockman Foundation, PI - Heimberger, A,
12/11/2018-12/10/2021, $510,245 ($166,685/year)
Co-Investigator, 15%, [18F]FAZA PET/CT for Monitoring Target Engagement of a Novel Complex I Inhibitor,
R01CA231506-01A1, NIH/NCI, PI - Piwnica-Worms D, 8/5/2019-7/31/2021, $457,500 ($228,750/year)
Project 2 Co-Leader, 25%, SPORE in Brain Cancer, P50CA127001-11A1, NIH/NCI, PI - Lang F, 9/1/2019-8/31/2024,
Principal Investigator, 10%, Angiogenesis Inhibited Tumors are Vulnerable to Inhibitor of Oxidative Phosphorylation, Uncle Kory Foundation, 11/1/2019-10/31/2020, $50,000 ($50,000/year)
Co-Investigator, 3 months, Collateral Genomic Deletions As Targetable Vulnerabilities in Cancer, RP140612, Cancer Prevention & Research Institute of Texas (CPRIT), PI - DePinho, 8/31/2014-8/30/2017, $285,000
Co-Principal Investigator, 3 months, Development of an Enolase inhibitor for 1p36 homozygously deleted GBM, NIH/NCI,
PI - Lang, Fueyo, 9/1/2014-8/31/2016, $50,000
Co-Principal Investigator, 1.8 months, Nerstian Probes as Vectors for Imaging and Therapeutic Modalities in Glioblastoma, NIH/NCI, PI - Lang, Fueyo, 9/1/2015-8/31/2016, $50,000
Principal Investigator, 1.44 months, ENO1-deletion as a target for personalized oncology: Collateral Lethality to the Clinic, National Comprehensive Cancer Network – Young Investigator Award, 7/1/2017-6/30/2019, $150,000 ($75,000/year)
Co-Principal Investigator, 1.2 months, Collateral Lethality of PTEN Deleted Castration Resistant Prostate Cancer, UT
MD Anderson SPORE in Prostate Cancer –Developmental Research Project, 9/1/2017-8/31/2018, $50,000
Co-Principal Investigator, 0.6 months, Collateral Lethality Targeting of PTEN Deletion in Glioblastoma, 2P50CA127001,
UT MD Anderson SPORE in Brain Cancer – Developmental Research Project, 9/1/2017-8/31/2018, $49,992 ($49,992/year)
Principal Investigator, Collateral Lethality Based Tumor Eradication via T-cell Activation, Institution Research Grant (IRG), 1/1/2018-1/31/2019, $75,000 ($75,000/year)
Principal Investigator, 3 months, Collateral Deletion of PANK1 as a Therapeutically Targetable Vulnerability in PTEN-Deleted Cancers, Elsa U Pardee Foundation, 1/1/2018-3/31/2019, $156,314 ($156,314/year)
Principal Investigator, 15%, Validation of Paralog Dependencies, Boehringer Ingelheim Pharmaceuticals, Inc.,
2/1/2018-6/30/2019, $93,750 ($93,750/year)
Principal Investigator, 10%, Collateral Lethality to the Clinic: A Clinical Candidate Targeting ENO1-deleted Cancers,
Dr. Marnie Rose Foundation, 2/13/2018-2/12/2019, $60,000 ($60,000/year)
Project 2 Co-Leader, 5%, Flagship 2 Project 2: Targeting Metabolic Vulnerabilities with Molecular Inhibitors of Oxidative Phosphorylation, The University of Texas MD Anderson Cancer Center - Glioblastoma Moon Shot, PI - Heimberger, Lang, de Groot, 9/1/2018-8/31/2019, $227,042 ($227,042/year)
Cancer Systems Imaging
The Cancer Systems Imaging department (CSI) resides within the Diagnostic Imaging division. CSI focuses on molecular imaging, functional genomics and high throughput technologies with a focus on mechanism-based fundamental, preclinical and clinical-translation studies of cancer.
The University of Texas MD Anderson Cancer Center's Diagnostic Imaging division has more than a dozen technologies available for radiologists to visualize tumors in both bone and soft tissue. From standard radiology to advanced techniques that can view the tiniest blood vessels, our radiologists take diagnosis, tumor staging and treatment planning to a whole new level.
The University of Texas MD Anderson Cancer Center
Cancer Systems Imaging
1881 East Road
Unit Number: 1907
Room Number: 3SCR4.3620
Houston, TX 77054-1901
Senior Administrative Assistant, Cancer Systems Imaging