Brian F Clem, Ph.D.

Education:

B.S., Major: Biology, Minor: Chemistry, Centre College, Danville, KY 2000
Ph.D., Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 2005
Postdoctoral Fellowship, Department of Medicine (Hematology/Oncology), University of Louisville, Louisville, KY 2009

Curriculum Vitae

Current Positions:

Dr. Don Miller Endowed Professor of Cancer Metabolism Research

Associate Professor of Biochemistry and Molecular Genetics

Associate Scientist, Brown Cancer Center

 

Contact Information:

Clinical Translational Research Building, Room 422
University of Louisville
505 Hancock St.
Louisville, KY 40202, USA
Phone 502-852-8427
Fax 502-852-3661
Email: brian.clem@louisville.edu

Research Description:

The Clem laboratory aims to understand the mechanisms by which tumors can alter their nutrient metabolism to support their rapid and expansive growth. These changes are primarily promoted by genetic mutations that lead to oncogenic activation and/or loss of tumor suppressor function. We have previously demonstrated a direct role of the retinoblastoma protein, which was the first identified tumor suppressor, in controlling specific metabolic pathways that allow for enhanced cell proliferation as well as protection from cellular stress. From our research, we ultimately intend to identify specific differences within tumor cells that may be selective targets for new anti-cancer therapies.

In collaboration with a computational biologist, biophysicist, and medicinal chemist, we are characterizing new inhibitors against metabolic targets that may have clinical activity in cancer patients. Using advanced compound screening methods, efficacy assays on human cancer in vitro and in vivo, and the ability to synthesize more potent molecules, we expect to generate unique anti-tumor chemotherapeutic strategies.

Literature Cited:

  1. Clem BF. RB in glutamine metabolism. Oncoscience, 1(5):304-305. 2014
  2. Yalcin, A, Clem, BF, Imbert-Fernandez, Y, Ozcan, SC, Peker S, O’Neal, J, Klarer, A, Clem, A, Telang, S, and Chesney, J. 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27. Cell Death and Disease, 5; e1337, 2014
  3. Imbert-Fernandez Y., Clem B.F., O’Neal J., Kerr D.A., Spaulding R.T., Lanceta L., Clem A., Telang S., Chesney J. Stimulation of glucose metabolism by estradiol is mediated by 6-phosphofructo-2-kinase (PFKFB3). Journal of Biological Chemistry. Mar28;289(13):9440-8 2014.
  4. Liu Y, Sanchez-Tillo E, Lu X, Huang L, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A, Dean DC. The ZEB1 Transcription Factor Acts in a Negative Feedback Loop with miR200 Downstream of Ras and Rb1 to Regulate Bmi1 Expression. Journal of Biological Chem. Feb 14;289(7):4116-25 2014.
  5. Reynolds MR, Lane AN, Robertson B, Kemp S, Liu Y, Hill BG, Dean DC, Clem BF. Control of glutamine metabolism by the tumor suppressor Rb.Oncogene. Jan 30;33(5): 556-66. 2014
  6. Klarer AC, O’Neal J, Imbert-Fernandez Y, Clem A, Ellis SR, Clark J, Clem B, Chesney J, Telang S. Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism. Cancer Metab. Jan 23;2(1):2. 2014
  7. Clem BF, O’Neal J, Tapolsky G, Clem A, Imbert-Fernandez Y, Kerr AD, Klarer AC, Redman R, Miller DM, Trent JO, Telang S, Chesney J. Targeting 6-Phosphofructo-2-Kinase (PFKFB3) as a Therapeutic Strategy against Cancer. Mol. Cancer Therapeutics. Aug;12(8):1461-70. 2013.
  8. Liu Y, Sanchez-Tillo E, Lu X, Huang L, Clem B.F., Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A, Dean DC. Sequential Inductions of the ZEB1 Transcription Factor Caused by Mutation of Rb and then Ras are required for Tumor Initiation and Progression.J Biol Chem. Apr 19;288(16):11572-80. 2013
  9. Liu Y, Sanchez-Tillo E, Lu X, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Postigo A,       Dean DC. Rb1 family mutation is sufficient for sarcoma initiation. Nature Communications. Oct       23;4:2650 2013.
  10. Clem, B.F.*, Chesney, J. Molecular Pathways: Regulation of Metabolism by RB. Clinical Cancer Res. Nov 15;18(22): 6096-100, 2012.
  11. Telang, S., Clem, B.F., Klarer, A.C., Clem, A.L., Trent, J.O., Bucala, R., Chesney, J. Small Molecule Inhibition of 6-Phosphofructo-2-Kinase Suppresses T Cell Activation. J. Transl. Med. May 16;10(1):95. 2012.
  12. Akter, S., Clem, B.F., Lee, H.J., Chesney, J., Bae, Y. Block Copolymer Micelles for pH-Controlled Delivery of Glycolytic Enzyme Inhibitors. Pharm. Res. Mar;29(3):847-55, 2012.
  13. Clem, B.F., Clem, A.L., Yalcin, A., Goswami, U., Telang, S., Trent, J.O., and Chesney, J. A Novel Small Molecule Antagonist of Choline Kinase-α That Simultaneously Suppresses MAPK and PI3K/AKT Signaling. Oncogene. Jul 28;30(30):3370-80, 2011.
  14. Clem, B.F., Telang, S., Clem, A., Yalcin, A., Meier, J., Simmons, A., Rasku, M., Arumugam, S., Dean, W.L., Eaton, J., Lane, A., Trent, J.O., and Chesney, J. Small Molecule Inhibition of 6-Phosphofructo-2-Kinase Activity Suppresses Glycolytic Flux and Tumor Growth. Mol. Cancer Therapeutics, 7(1):110-20, 2008.
  15. Clem, B.F., Hudson, E., Clark, B.J. Cyclic Adenosine 3’,5’-Monophosphate (cAMP) Enhances cAMP-Responsive Element Binding (CREB) Protein Phosphorylation and Phospho-CREB Interaction with the Mouse Steroidogenic Acute Regulatory (StAR) Protein Gene Promoter. Endocrinology.146(3):1348-1356. 2005.

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