Adam Lerner, MD

Professor of Medicine

Education:

MD – Yale Medical School

General field of research:

Breast cancer, hematologic malignancies

Affiliations other than medicine:

Evans Center for Interdisciplinary Biomedical Research
Department of Pathology
Hematology Training Program

Contact information:

Office
EBRC 427, 650 Albany Street, Boston, MA
Phone: (617) 638-7504

Lab
EBRC 420, 650 Albany Street, Boston, MA
Phone: (617) 638-7543
Fax: (617) 638-7530

lernwara@bu.edu

Research group information

Anthony Makkinje PhD, Senior Research Associate – tapline@earthlink.net
John Meyers, PhD, Asst. Professor – johnm@bu.edu
Richard Near PhD, Research Asst.Prof. – rocket1@bu.edu
Prayag Patel, BU undergraduate student – prayag@bu.edu

Keywords:

Breast cancer; Anti-estrogen resistance; Chronic lymphocytic leukemia; Cyclic nucleotide phosphodiesterases

Summary of research interest:

Anti-estrogen resistance in breast cancer: We are trying to determine why over-expression of two focal adhesion proteins, AND-34/BCAR3 and p130Cas/BCAR1 result in anti-estrogen resistance in human breast cancer cell lines. Both of these proteins have been shown to confer resistance to hormonal therapy and poor prognosis in patients with breast cancer.Our work has revealed an important role for BCAR3 in regulating p130Cas-mediated signaling pathways in murine and human cells.

cAMP-mediated signaling has the capability to augment the sensitivity of lymphoid malignancies to a variety of therapeutic agents. We have identified a potentially clinically realistic approach to augmenting cAMP signaling in chronic lymphocytic leukemia cells by treatment with selective inhibitors of the type 4 cAMP phosphodiesterase family. Such drugs augment sensitivity of CLL cells to glucocorticoids as well as agents that induce DNA damage. We are currently focused on elucidating the mechanism by which such synergistic apoptotic effects occur.

Recent publications:

Meyers J.A., D.W. Su, A. Lerner. 2009. CLL, B and T cells differ in their response to cyclic nucleotide phosphodiesterase inhibitors. J. Immunol 182:5400-5411. (PMCID: PMC2676892)

Meyers J.A., J. Taverna, J. Chaves, A. Makkinje, A. Lerner. 2007. PDE4 inhibitors augment levels of glucocorticoid receptor in B cell chronic lymphocytic leukemia but not in normal circulating hematopoietic cells. Clinical Cancer Research 13: 4920-4927. (PMCID: PMC2656255).

Lerner A., P. Epstein. 2006. Cyclic nucleotide phosphodiesterases as targets for treatment of haematological malignancies. Biochemical Journal 393: 21-41. (PMCID: PMC1383661).

Tiwari S., K. Felekkis, E.Y. Moon, A. Flies, D. Sherr, A. Lerner. 2004. Among circulating hematopoietic cells, B-CLL uniquely expresses functional EPAC1 but EPAC1-Mediated Rap1 activation does not account for PDE4 inhibitor-induced apoptosis. Blood 103:2661-2667. (PMID: 14615375).

Makkinje A., R. I. Near, G. Infusini, A. Bloom, D. Cai, P. Vanden Borre, C.E. Costello, A. Lerner. 2009. AND-34 regulates late-phase, adhesion-dependent p130Cas serine phosphorylation and breast cancer cell growth pattern. Cellular Signaling 21: 1423-35.

Near R.I., R.S. Smith, P.A. Toselli, T. Freddo, A. Bloom, P. Vanden Borre, D. Seldin, A. Lerner. 2009. AND-34/BCAR3 is required for structural integrity of the adult mouse lens. Molecular Vision 15:685-699.

Near R.I., Y. Zhang, A. Makkinje, P. Vanden Borre, A. Lerner. 2007. AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology. J. Cell. Physiol 212: 655-665. (PMCID: PMC2640322).

Felekkis K.N., R.P. Narsimhan, A.F. Castro, L.A. Quilliam, A. Lerner. 2005. AND-34 activates phosphatidylinositol 3-kinase and induces antiestrogen resistance in a SH2 and GEF-like domain-dependent manner. Molecular Cancer Research 3; 32-41. (PMID: 15671247).

Technologies available for sharing upon request:

Phospho-flow cytometry (please contact John Meyers); Phospho-amino acid analysis (Please contact Anthony Makkinje)