Lawrence B. Gardner

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Lawrence Gardner

Associate Professor, Department of Medicine;Associate Professor, Department of Biochemistry and Molecular Pharmacology
Perlmutter Cancer Center
NYU Hematology Associates

Contact Info

Address
522 First Avenue
New York, NY 10016

212/263-8038

Research Summary

We study the effect of low oxygen (hypoxia) on cell cycle regulation, apoptosis, cellular metabolism, and development. Many tumors are severely hypoxic, and hypoxic tumors have a poorer prognosis than non-hypoxic tumors. While most normal cells growth arrest when hypoxic, we have demonstrated that some neoplastic cells, as well as cells we have manipulated with oncogenes, can proliferate even when hypoxic. Using biochemistry, molecular biology, and cell biology techniques we have delineated two specific cell cycle checkpoints that are activated in hypoxic cells: an Rb mediated G1 arrest, and an S phase arrest that is due to the suppression of the initiation step of DNA replication. We are determining how the DNA initiation complex is altered in hypoxic cells, and the role of the ATR kinase (which we have observed is activated in hypoxic cells) in this alteration. We have also determined that the helix-loop-helix inhibitor, Id-1, is transcriptionally down-regulated in hypoxic cells. This down-regulation is dependent on activation of the activation of the unfolded-protein response, and we and are exploring the mechanism and significance of this observation.

Research Interests

Mechanism and Significance of Hypoxic Regulation of Cell Cycle

PP6C Hotspot Mutations in Melanoma Display Sensitivity to Aurora Kinase Inhibition
Gold, Heidi L; Wengrod, Jordan; de Miera, Eleazar Vega-Saenz; Wang, Ding; Fleming, Nathaniel; Sikkema, Lisa; Kirchhoff, Tomas; Hochman, Tsivia; Goldberg, Judith D; Osman, Iman; Gardner, Lawrence B
2014-04-22; 1541-7786,Molecular cancer research - id: 883502, year: 2014 Journal Article

Identification and Characterization of Small Molecules That Inhibit Nonsense-Mediated RNA Decay and Suppress Nonsense p53 Mutations
Martin, Leenus; Grigoryan, Arsen; Wang, Ding; Wang, Jinhua; Breda, Laura; Rivella, Stefano; Cardozo, Timothy; Gardner, Lawrence B
2014-06-10; 0008-5472,Cancer research - id: 1032302, year: 2014 Journal Article

The clinical and biologic impact of PPP6C mutations in melanoma
Gold, H L; Wengrod, J; Tian, J; Vega-Saenz, de Miera E; Nadeem, Z; Fleming, N H; Shapiro, R; Hernando-Monge, E; Gardner, L; Osman, I
2013-07-25; 0732-183x,Journal of clinical oncology - id: 451882, year: 2013

Regulation of nonsense-mediated mRNA decay: Implications for physiology and disease
Karam, Rachid; Wengrod, Jordan; Gardner, Lawrence B; Wilkinson, Miles F
2013-06-10; 0006-3002,Biochimica & biophysica acta - id: 368202, year: 2013 Journal Article

Inhibition of nonsense-mediated RNA decay activates autophagy
Wengrod, Jordan; Martin, Leenus; Wang, Ding; Frischmeyer-Guerrerio, Pamela; Dietz, Harry C; Gardner, Lawrence B
2013-07-01; 0270-7306,Molecular & cellular biology - id: 402122, year: 2013 Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't