Levi J. Beverly, PhD

Assistant Professor of Medicine; Associate Scientist, James Graham Brown Cancer Center

Research Program
Molecular Targets

B.S., Biology, University of Cincinnati, Cincinnati, OH, 2000
Ph.D., Molecular Biology, Biochemistry & Microbiology, University of Cincinnati, OH, 2007

Research and Professional Experience
Graduate Research Fellow, laboratory of Anthony Capobianco, University of Cincinnati, Cincinnati, OH

Post-doctoral Fellow, laboratory of Harold Varmus, National Institutes of Health, Bethesda, MD

Assistant Professor, Department of Medicine, University of Louisville, Louisville, KY

Associate Scientist, James Graham Brown Cancer Center, University of Louisville, Louisville, KY

Assistant Professor, Associate Member, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY

Research Interest
The Beverly lab is interested in using mouse models of human cancer to elucidate the mechanisms of tumor initiation, progression and regression following therapeutic intervention.  To this end, we have adopted a philosophy of combining the mouse models, with biochemistry, molecular biology and cell culture to dissect signaling pathways and cellular processes.  Using information gathered from in vitro experimentation, we proceed back into our mouse models to determine how our understanding of the disease initiation, progression or regression has advanced.  To this end the research in the lab can be broken down into three broad areas of interest:

1.     Characterization of BCL2-family interacting proteins

Current work has focused on understanding the biochemical and molecular differences between the anti-apoptotic BCL2 family of proteins.  Initial experiments, in vivo, demonstrated that there were quantitative differences in the cooperative potential of the six BCL2-family members in a mouse model of MYC-driven leukemogenesis.  This observation has led to an intense examination into the biochemical specificities of each individual BCL2-like protein.  As an example, using an unbiased proteomic approach we have identified a novel protein Ubiquilin1 that is capable of interacting with a single BCL2 family member, BCLb (BCL2L10).  The interaction between BCLb and Ubiquilin1 leads to the mono-ubiquitination and stabilization of BCLb.  Going back into the mouse model demonstrated that stabilization of BCLb increases oncogenic potential.

2.   Identify genes capable of cooperating in tumor progression and initiation

Separating genes and pathways that play a direct role in the initiation and/or progression of cancer (so-called drivers) from those genes and pathways that are inconsequential in cancer biology (so-called passengers) is a daunting task in the research world of high through-put technologies and high resolution ‘next generation’ sequencing.  By combining multiple publicly available datasets, we are interested in identifying novel genes that, when mutated, contribute to cancer progression and/or initiation.  Using the techniques of the lab we are now testing directly whether or not these genes are involved in tumorigenesis and what biological processes these novel proteins regulate.

3.   Pre-clinical development of novel synergistic drug combinations.

      In collaboration with the National Chemical Genomics Center at the National Institutes of Health we have been performing screens to identify novel combinations of drugs that, when used together, lead to synergistic killing of cancer cell lines.  Thus far, we have performed a number of such screens and have begun to either characterize the synergistic combinations of drugs, or identify collaborators that have expertise in the pathways affected by the individual drugs.  In addition, we will use our mouse models to validate and optimize pre-clinical effectiveness of these drug combinations.  Our ultimate goals from this project are two-fold; first, we hope to gain insight into the signaling pathways that work in combination to maintain cancer cell viability and second, and most importantly, we hope to find novel and effective drug combinations that we can move into the clinical space for testing on human patients.


Ascano JM, Beverly LJ, Capobianco AJ.  The C-terminal PDZ-ligand of JAGGED1 is essential for cellular transformation.  J Biol Chem 278(10):8771-9, 2003


Beverly LJ, Capobianco AJ.  Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in Notch(IC)-induced T cell leukemogenesis.  Cancer Cell 3(6):551-64, 2003


Beverly LJ, Capobianco AJ.  Targeting promiscuous signaling pathways in cancer: another Notch in the bedpost.  Trends Mol Med 10(12):591-8, 2004


Beverly LJ, Felsher DW, Capobianco AJ.  Suppression of p53 by Notch in lymphomagenesis: Implications for initiation and regression.  Cancer Res 65:(16):7159-68, 2005


Carlson TF, Yan Y, Wu X, Lam MT, Tang GT, Beverly LJ, Messina LM, Capobianco AJ, Werb Z, Wang R.  Endothelial expression of constitutively active Notch4 elicits reversible arteriovenous malformations in adult mice.  Proc Natl Acad Sci USA 102(28):9884-9, 2005


Beverly LJ, Ascano JM, Capobianco AJ.  Expression of JAGGED1 in T-lymphocytes results in thymic involution by inducing apoptosis of thymic stromal epithelial cells.  Genes Immun 7(6):476-86, 2006


Sharma VM, Calvo JA, Draheim KM, Cunningham LA, Hermance N, Beverly L, Krishnamoorthy V, Bhasin M, Capobianco AJ and  Kelliher MA.  Noth1 contributes to mouse T cell leukemia by directly inducing the expression of c-myc.  Mol Cell Biol 26(21):8022-31, 2006


Spaulding C, Reschly EJ, Zagort DE, Yashiro-Ohtani Y, Beverly LJ, Capobianco A, Pear WS, Kee BL.  Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas.  Blood 110(7):2650-8, 2007


Podsypanina K, Politi K, Beverly LJ, Varmus HE.  Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras.  Proc Natl Acad Sci USA 105(13):5242-7, 2008


Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambartzumyan D, Varmus HE.  Seeding and propagation of untransformed mouse mammary cells in the lung.  Science 321(5897):1841-4, 2008


Beverly LJ, Varmus HE.  MYC-induced leukemogenesis is accelerated by all members of the anti-apoptotic BCL family.  Oncogene 28(9):1274-9, 2009


Pinnix CC, Lee JT, Liu ZJ, McDaid R, Balint K, Beverly LJ, Brafford PA, Xiao M, Himes B, Zabierowski SE, Yashiro-Ohtani Y, Nathanson KL, Bengston A, Pollock PM, Weeraratna AT, Nickoloff BJ, Pear WS, Capobianco AJ, Herlyn M.  Active Notch1 confers a transformed phenotype to primary human melanocytes.  Cancer Res 69(13):5312-20, 2009


Beverly LJ.  Regulation of anti-apoptotic BCL2-proteins by non-canonical interactions.  J Cellular Biochem, in press.

Contact Information

CTR Building
505 South Hancock Street
Louisville, KY 40202
(502) 852-8968