Manning Laboratory
H. Charles Manning, Ph.D.
Principal Investigator
Areas of Research
- Cancer Metabolism Research
- Chemical Inhibitors
- Colorectal Cancer Research
- Drug Development Research
- Early Cancer Detection Research
- Gene Expression Research
- Imaging Research
- Liver Cancer Research
- Pancreatic Cancer Research
- Targeted Therapy Research
Welcome to the Manning Laboratory!
Our research
The overarching objective of the Manning Laboratory is to develop new positron emission tomography (PET) imaging tracers and therapies that enable non-invasive visualization and quantification of specific molecular events in cancer cells and the targeting of these events for treatment of various types of cancer. A wealth of proteogenomic information has provided a deep understanding of the molecular pathogenesis of human cancer and has led to improved classification systems of this disease. However, with notable exceptions, accurately diagnosing cancer and subsequently matching patients with optimum therapeutic regimens remain challenging. Complementary to precision medicine approaches (e.g., liquid biopsy), PET leverages labeled, biologically active compounds, or ‘tracers’, to provide quantitative measures of tumor phenotype. Uniquely, PET quantifies functional biological processes, such as the activity of biological targets, as opposed to simply target expression, on a lesion-by-lesion basis. Our goals are to discover, rigorously validate, and translate new tracers to elucidate the molecular underpinnings of tumors with PET and to use quantitative PET imaging to advance precision cancer medicine. Our current efforts seek PET tracers to improve cancer diagnosis and to quantify early responses of tumors to therapy. Our lab is very interested in quantifying cellular metabolism non-invasively, including high-affinity ligands for receptor-based targets and metabolic substrate transporters elevated in cancer cells. Our lab is also developing pharmacological inhibitors targeting cancer cell metabolism.
Selected publications
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Cohen AS, Grudzinski J, Smith GT, Peterson TE, Whisenant JG, Hickman TL, Ciombor KK, Cardin D, Eng C, Goff LW, Das S, Coffey RJ, Berlin JD, Manning HC. First-in-human PET imaging and estimated radiation dosimetry of L-[5-11C]-glutamine in patients with metastatic colorectal cancer. J Nucl Med. 2021 Apr 30:jnumed.120.261594. doi: 10.2967/jnumed.120.261594. Epub ahead of print. PMID: 33931465.
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Reinfeld BI, Madden MZ, Wolf MM, Chytil A, Bader JE, Patterson AR, Sugiura A, Cohen AS, Ali A, Do BT, Muir A, Lewis CA, Hongo RA, Young KL, Brown RE, Todd VM, Huffstater T, Abraham A, O'Neil RT, Wilson MH, Xin F, Tantawy MN, Merryman WD, Johnson RW, Williams CS, Mason EF, Mason FM, Beckermann KE, Vander Heiden MG, Manning HC, Rathmell JC, Rathmell WK. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature. 2021 May;593(7858):282-288. doi: 10.1038/s41586-021-03442-1. Epub 2021 Apr 7. PMID: 33828302; PMCID: PMC8122068.
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Edwards DN, Ngwa VM, Raybuck AL, Wang S, Hwang Y, Kim LC, Cho SH, Paik Y, Wang Q, Zhang S, Manning HC, Rathmell JC, Cook RS, Boothby MR, Chen J. Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer. J Clin Invest. 2021 Feb 15;131(4):e140100. doi: 10.1172/JCI140100. PMID: 33320840; PMCID: PMC7880417.
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Cohen AS, Li J, Hight MR, McKinley E, Fu A, Payne A, Liu Y, Zhang D, Xie Q, Bai M, Ayers GD, Tantawy MN, Smith JA, Revetta F, Washington MK, Shi C, Merchant N, Manning HC. TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions. Clin Cancer Res. 2020 Nov 15;26(22):5914-5925. doi: 10.1158/1078-0432.CCR-20-1214. Epub 2020 Sep 15. PMID: 32933996; PMCID: PMC7669725.
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Cohen AS, Geng L, Zhao P, Fu A, Schulte ML, Graves-Deal R, Washington MK, Berlin J, Coffey RJ, Manning HC. Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer. Transl Oncol. 2020 Oct;13(10):100828. doi: 10.1016/j.tranon.2020.100828. Epub 2020 Jul 8. PMID: 32652471; PMCID: PMC7348062.
Funding
Manning Laboratory funding includes:
R01 CA239694 (Manning)
NIH/NCI
09/01/2020 – 08/31/2024
Quantitative PET Imaging of Hepatocellular Carcinoma (HCC)
5U24 CA220325-02 (Manning)
NIH/NCI
09/14/2018 – 08/31/2023
MD Anderson PREDICT
P50CA236733 (Coffey Jr.); Role: Project 2 Leader; Co-Investigator
Vanderbilt University Medical Center/NIH/NCI
07/09/2019 – 05/31/2024
Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal Cancer
RP200046 (Manning)
Cancer Prevention and Research Institute of Texas
06/01/2020 – 05/31/2025
CPRIT Recruitment – Established Investigator