Faculty Directory
Research Connections

Faculty Directory
Research Connections

Information For

Alumni
Donors
Faculty
Postdocs
Students (Prospective, Current)
Visitors

Quick Links

About
Administration
Careers
Departments & Centers
Directory
Education & Admissions
Events

Find Faculty
Giving
Health
Intranet
Library
Research
Webmail

News & Media

Newsroom
Blog
Einstein in the News
Expert List for Media
Features

Magazine
Multimedia
News Releases
Research Briefs
Social Media Hub

Faculty Profile

Montefiore Einstein Home
Albert Einstein College of Medicine
Faculty Directory
Jonathan M. Backer, M.D.

Jonathan M. Backer, M.D.

Professor, Department of Molecular Pharmacology

Professor, Department of Biochemistry

Chair Department of Molecular Pharmacology

William S. Lasdon Chair in Pharmacology Department of Molecular Pharmacology

Associate Director, Shared Resources Montefiore Einstein Comprehensive Cancer Center

Area of Research: Signal transduction; Phosphoinositide kinases; Tumor metastasis; Vesicular trafficking; macropinocytosis

Contact Information

718.430.2153718.430.3749jonathan.backer@einsteinmed.edu

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 230
Bronx, NY 10461

Research Profiles

More Resources: Department of Molecular Pharmacology

Is this your profile? Edit profile

Professional Interests

SIGNALING BY PHOSPHOINOSITIDE KINASES

Phosphoinositide 3-kinases (PI3Ks) are lipid kinases that mediate signaling downstream from receptor tyrosine kinases and G-protein coupled receptors (GPCRs). They are important regulators of cellular proliferation, motility, apoptosis, and vesicular trafficking. Mutational activation of PI3Ks is commonly found in human cancers. We are interested in how the altered regulation of PI3K contributes to human cancer.

1. PI3Ks in breast cancer. Class I PI3Ks are the sole source of the signaling lipid phosphoinositide-3,4,5-P₃ (PIP₃) in cells, which activates downstream kinases like Akt, small GTPases like Rac and Cdc42, and signaling enzymes like Phospholipase C. The PI3Kbeta isoform of PI3K is unique among Class I PI3Ks in that it (a) is activated by binding to receptor tyrosine kinases, (b) is also activated by direct binding to Gbeta-gamma subunits downstream of activated GPCRs and to the small GTPase Rac1, and (c) specifically binds to the small GTPases Rab5, which regulates vesicular trafficking in the early endosome. We have identified point mutants that disrupt PI3Kbeta binding to either Gbeta-gamma or Rab5, and have shown that these mutants block tumor cell invasion in cell culture and animal models of breast cancer metastasis.

Our current work focusses on the mechanisms by which PI3Kbeta regulates breast cancer invasion, particularly its role in stromal cells such as macrophages and platelets. We have developed knock-in mice expressing the mutations that inhibit PI3Kbeta binding to either Gbeta-gamma or Rab5, and we are studying how these mutations affect the behavior of primary macrophages and platelets. We have shown that PI3Kbeta mutations inhibit the ability of both platelets and macrophages to stimulate the invasive behavior of tumor cells. In a parallel set of experiments, we have shown that mutation or knockout of PI3Kbeta in tumor cells inhibits invasion and metastasis, and also blocks macropinocytosis. This is a fluid-phase endocytic pathway that provides nutrients to support tumor growth under hypoxic or poorly vascularized conditions. Taken together, our findings suggest that PI3Kbeta could be an important drug target in the treatment of tumor growth and metastasis.

2. S100A4 signaling in macrophages. In collaboration with Dr. Anne Bresnick (Biochemistry), we are studying the regulation of cellular motility and invasion by the dimeric calcium-binding protein S100A4. S100A4 is prometastatic when expressed in tumor cells. We have recently found that S100A4 also regulates invasion and matrix degradation by both tumor cells and macrophages, and it is required for platelet stimulation of invasion by tumor cells. Our current work uses genomic, proteomic and cell biological methods to study how macrophage S100A4 regulates vesicular trafficking pathways that contribute to macrophage motility and invasion.

Selected Publications

Jakubik, CT, Weckerly, CC, Hammond, GRV, Bresnick, AR, and Backer, JM. PIP₃ abundance overcomes PI3K signaling selectivity in invadopodia. FEBS Letters 2022 596:417-426

Salloum, G., Jakubik, CT, Erami, Z., Heitz, SD, Bresnick, AR, and Backer, JM. PI3Kβ is selectively required for growth factor-stimulated micropinocytosis. (2019) J. Cell Sci. 132(16). pii: jcs231639

Heitz, SD, Hamelin, DJ, Hoffmann, RM, Greenbeerg, N, Salloum, G., Eramie, Z., Khalil, B., Shymanets,A, Steidle, EA, Gong, GQ, Nurrnberg, B, Burke, JE, Flanagan, JU, Bresnick, AR, and Backer, JM. A single discrete Rab5-binding site in phosphoinositide 3-kinase β is required for tumor cell invasion (2019) J. Biol. Chem 294:4621-4633.

Erami, Z., Heitz, SD. Bresnick AR, and Backer, JM. PI3K β links integrin activation and PI(3,4)P₂ production during invadopodial maturation (2019) Molecular Biology of the Cell 15:2367-2376.

Quick Links

Faculty Profile

Jonathan M. Backer, M.D.

Contact Information

Professional Interests

SIGNALING BY PHOSPHOINOSITIDE KINASES

Selected Publications

Selected Publications

Related News

News Release

Montefiore Einstein Cancer Center Receives $10 Million Grant from the National Cancer Institute to Study Lung Metastasis in Breast Cancer

News Release

Montefiore Einstein Cancer Center Researchers Receive Price Family Foundation Health Equity Research Awards

Feature

Dr. Jonathan Backer: Molecules by Day, Music by Night

News Release

Dr. Jonathan M. Backer Named Chair of Molecular Pharmacology at Albert Einstein College of Medicine