Brian Clem, Ph.D

Assistant Professor; Director of Graduate Admissions 

319 Abraham Flexner Way, Louisville KY, 40202

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Research Interests

    • Regulation of tumor metabolism
    • Mechanism of action of pRB on controlling nutrient pathways
    • Development of novel anti-metabolic antagonists for cancer treatment

     Our lab 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. 

      Laboratory Personnel

        Miriam Reynolds

          Traci Kruer, Ph.D.

          Susan Dougherty

          Selected Publications

            Clem BF. RB in glutamine metabolism. Oncoscience, 1(5):304-305. 2014

              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 PMCID: 4123086

              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. PMCID: 3979387

              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. PMCID: 3924277

              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 PMCID: 3918885

              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 PMCID: 3913946

              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. PMCID: 3742633  *Cover

              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 PMCID: 3630860

              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. PMID: 24150016