Faculty Profile

Dr. Edward L. Schwartz, Ph.D.

Edward L. Schwartz, Ph.D.

Professor, Department of Medicine (Oncology)

Professor, Department of Molecular Pharmacology

Areas of Research: Identification of new targets and novel agents to treat lung cancer.

Professional Interests

The most recent focus of my lab is the discovery of new targets for drug design and development for the treatment of lung cancer. Small cell lung cancer (SCLC) is characterized by aggressive growth, frequent metastases, the development of chemotherapy resistance, and has a five-year survival rate of less than 5%. The identification of driver mutations and their corresponding targeted drugs have led to significant improvements in the treatment of many solid tumors; however, similar advances have not been made in the treatment of SCLC. A unique feature of SCLC is the near uniform bi-allelic mutation and inactivation of tumor suppressor genes RB1 and TP53 to drive tumorigenesis. This defining feature of the disease has not led to a targeted therapy, however, since genetically inactivated RB1 and TP53 cannot be reactivated, nor is it feasible to reintroduce the wild-type genes into all tumor cells clinically. Our lab is interested in identifying key signaling pathways that are activated in RB1-deficient cells, and then to design and test pharmacologic agents that inhibit these pathways, restoring the lost function(s) of RB1, and causing tumor regressions.

 In addition to tissue culture studies, we utilize several animal models of cancer, including genetically-modified mice to determine the role of key proteins in SCLC tumorigenesis, conditional mouse models in which expression of critical genes can be turned off after the SCLC tumors have become established and metastasized, and patient-derived xenografts (PDXs) in which tumor specimens go directly from the patient into the mouse. These approaches help to validate potential gene targets for drug therapy, and to establish the efficacy of established and novel targeted drugs.

 We also have established collaborations to identify new small molecules that bind to promising regions of the targeted protein and protein complexes. These studies use computational chemistry, in silico modeling, virtual library screening, and medicinal chemistry syntheses. Promising compounds are tested for antitumor activity in mouse and human lung cancer models, with the ultimate objective of developing them as cancer chemotherapy drugs.

Selected Publications

Sironi J, Aranda A, Nordstrøm L, and Schwartz EL. Lysosome membrane permeabilization and disruption of mTOR-lysosome interaction are associated with the inhibition of lung cancer cell proliferation by a chloroquinoline analog. Molecular Pharmacology, 2019; 95:127-138.

Cheng H, Zou Y, Ross JS, Wang K,  Liu X, Halmos B, Ali SM, Liu H, Verma A, Montagna C, Chachoua A, Goel S, Schwartz EL, Zhu C, Shan J, Yu Y, Gritsman K, Yelensky R, Lipson D, Otto G, Hawryluk M, Stephens PJ, Miller VA, Piperdi B, Perez-Soler R. RICTOR amplification defines a novel subset of lung cancer patients who may benefit from treatment with mTOR1/2 inhibitors. Cancer Discovery, 2015; 5:1262-70.

Nordstrøm LU, Sironi J, Aranda E, Maisonet J, Perez-Soler J, Wu P and Schwartz EL. Discovery of  autophagy inhibitors with antiproliferative activity in lung and pancreatic cancer cells. ACS Medicinal Chem. Letters 2015; 6:134-9.

Zou Y, Ling YH, Sironi, J, Schwartz EL, Perez-Soler R, Piperdi B. (2013) The autophagy inhibitor chloroquine overcomes the innate resistance to erlotinib of non-small cell lung cancer cells with wild-type EGFR. J. Thoracic Oncology, 8:693-702.

Pula G, Dunn WB, Garonna E, Watson KE, Hirano M, Pizzorno G, Schwartz EL, el Kouni MH, Wheeler-Jones CPD. (2010) Paracrine stimulation of endothelial cell motility and in vitro wound repair by platelet-derived deoxyribose-1-phosphate. Arteriosclerosis, Thrombosis, and Vascular Biology. 30:2631-8.

Lu H, Klein RS and Schwartz EL (2009) Anti-angiogenic and anti-tumor activity of a novel thymidine phosphorylase inhibitor, 6-(2-aminoethyl)amino-5-chlorouracil (AEAC), in combination with the VEGF-Trap. Clinical Cancer Research, 15: 5136-5144.

Schwartz EL (2009) Anti-vascular actions of microtubule-binding drugs.  Clinical Cancer Research 15:2594-2601.

Murtagh J, Lu H and Schwartz EL (2006)  Taxotere-induced inhibition of endothelial cell migration is a result of Hsp90 degradation.  Cancer Research 66:8192-8199.

Lu, H, Murtagh J and Schwartz EL (2006) The microtubule binding drug laulimalide inhibits VEGF-induced human endothelial cell migration, and is synergistic when combined with Taxotere.  Molecular Pharmacology 69:1207-1215.

Hotchkiss, KA, Ashton AW and Schwartz EL (2003) The angiogenic factors thymidine phosphorylase and 2-deoxyribose stimulate human endothelial cell migration by activation of integrins alpha-5 beta-1 and alpha-v beta-3.  J. Biological Chemistry 278:19272-19279.

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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Block, Room 614
Bronx, NY 10461

Tel: 718.430.8864
Fax: 718.430.2044
edward.schwartz@einstein.yu.edu

Research Information