David J. Bearss
Professor of Biology
B.A. Brigham Young University
Ph.D. University of Texas Health Sciences Center, San Antonio
David Bearss's PubMed Literature Search
Research
My research is focused on the development of new approaches utilizing structure-based drug design and computational modeling of small molecule-protein interactions to develop new drugs for the treatment of cancers.
Our group has established that the utilization of computational approaches with structure-based drug discovery has several key synergies not yet realized from existing lead-identification systems:
1. The ability to identify new pathways of significant and emerging importance and determine potential drugability.
2. The ability to harness the power of supercomputing networks to computationally screen large virtual chemical libraries and reduce them to enriched sublibraries composed of compounds with predicted activity and "druglike" properties.
3. The ability to leverage phenotype-based screening of enriched sublibraries to empirically select lead molecules based on in vivo therapeutic effect.
4. The ability to integrate the discovery process with workflows of information utilizing information from genomic, proteomic and medical records from individual patients disease profiling.
We are pursuing several projects that demonstrate how our approach to drug discovery can be leveraged to explore new molecular targets. These projects include:
1. Epigenetic Reprogramming of Cancer Cells by Targeting DNA Methylation Dynamics
2. Mechanisms of Sensitivity to PDK1 Inhibition in Cancer Cells
3. The role of the Receptor Tyrosine Kinase Axl in Pancreatic Cancer Invasion and Metastasis.
4. Targeting the Histone Lysine Demethylase LSD1 in Breast Cancer and Sarcomas
5. Reversal of Drug Resistance in Multiple Myeloma by Targeting NEK2.
6. Developing Bone Partitioning Drugs Targeting the Tyrosine Kinase BTK for the Treatment of Multiple Myeloma.
7. Characterization of Inhibitors of ETS Family Proteins in Mutant ras Positive Cancers.
References
1. Chung JY, Davis JA, Price B, Staley DM, Wagner MV, Warner SL, Bearss DJ, Hansen MDH (2011) Competitive enhancement of HGF-induced epithelial scattering by accessory growth factors. Exp. Cell Res 317(3):307-18
2. Trevor KT, Combs D, Al-Obeidi A, Mahadevan D, Welsh JW, Bearss DJ, Morgan SS, Cranmer LD (2011) MP470, a novel multi-targeted kinase inhibitor for the treatment of synovial sarcoma. BMC Cancer, submitted
3. Kausar Begam Riaz Ahmed KBR, Steven L. Warner SL, Andrew Chen A, Eric S. Gourley ES, Xiaohui Liu X, Hariprasad Vankayalapati H, Roberto Nussenzveig R, Josef T. Prchal JT, David J. Bearss DJ, Charles J. Parker CJ (2011) In Vitro and In Vivo Characterization of SGI-1252, a Small Molecule Inhibitor of JAK2. Exp Hematol 39(1):14-25
4. Lavelle D, Saunthararajah Y, Vaitkus K, Singh M, Banzon V, Phiasivongsva P, Redkar S, Kanekal S, Bearss D, Shi C, Inloes R, DeSimone J (2010) S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis). J Transl Med 8:92
5. Chuang JC, Warner SL, Vollmer D, Vankayalapati H, Redkar S, Bearss DJ, Qiu X, Yoo CB, Jones PA (2010) S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther 9(5):1443-50
6. Welsh JW, Mahadevan D, Ellsworth R, Cooke L, Bearss D, Stea B (2009) The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma cells. Radiat Oncol 4:69
7. Mumenthaler SM, Ng PYB, Hodge A, Bearss D, Berk G, Kanekal S, Redkar S, Taverna P, David B, Agus DB, Jain A (2009) Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther 8(10):2882-93
8. Chen LS, Redkar S, Bearss D, Wierda WG, Gandhi V (2009) Pim kinase inhibitor, SGI-1776, induces apoptosis in CLL lymphocytes. Blood 114(19):4150-7
9. Qi W, Cooke LS, Stejska A, Riley C, Della Croce K, Saldanha JW, Bearss D, Mahadevan D (2009) MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer 9:142
10. Warner SL, Munoz MM, Bearss DJ, Grippo P, Han H, Von Hoff DD (2008) Pdx-1-Driven Overexpression of Aurora A Kinase Induces Mild Dysplasia of Pancreatic Ducts near Islets in Transgenic Mice. Pancreas 37(3):e39-44
11. Mahadevan D, Cooke L, Riley C, Swart R, Simons B, Della Croce K, Wisner L, Iorio M, Shakalya K, Garewal H, Nagle R, Bearss D (2007) A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene 7;26(27):3909-19
Updated 6/8/2011
