Photo of Andrius Kazlauskas,  PhD

Andrius Kazlauskas, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 912-2517
Fax: (617) 912-0101


andrius_kazlauskas@meei.harvard.edu

Andrius Kazlauskas, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Professor, Ophthalmology, Harvard Medical School
  • Senior Scientist, SERI, Schepens Eye Research Institute

Research Abstract

I am a basic scientist who devotes the majority (90%) of his time and attention to investigating intracellular signaling pathways that govern cellular responses. The resulting insights are used to advance our understanding of pathology, and to develop new therapeutic options for patients afflicted by disease. Intrinsic to this type of undertaking is the training of postdoctoral fellows, graduate students and clinical fellows. The remainder of my time (10%) is devoted to administrative activities and traditional (classroom-based) teaching of graduate and undergraduate students.

My laboratory is contributing to two research areas: intracellular signaling events that govern angiogenesis, and the role of growth factors in human disease. The angiogenesis projects are developing from our recent discovery of an internal destabilization pathway that controls the stability of blood vessels. We are identifying essential components of this pathway, and assessing their role in the pathogenesis of endemic, blinding conditions such as proliferative diabetic retinopathy and neovascular age-related macular degeneration. The growth factor projects emanate from our surprising observation that a non-traditional route to activate growth factor receptors is particularly important for the appearance of pathology. These findings have provided new opportunities to develop effective therapeutic strategies and thereby improve health care and the quality of life for patients.

In summary, the overall goal of my research is to elucidate the principles by which intracellular signaling controls the behavior of cells, and thereby provide the conceptual foundation for development of improved therapeutic options, especially in the field of ophthalmology.

 

Publications

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  • Jacobo SM, Kazlauskas A. Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels. J Biol Chem 2015; 290:6349-60. PubMed
  • Lei H, Qian C, Lei J, Haddock LJ, Mukai S, Kazlauskas A. RasGAP antagonizes signaling, cellular responses and pathology driven by indirectly activated PDGFR. Mol Cell Biol 2015. PubMed
  • Pennock S, Haddock LJ, Eliott D, Mukai S, Kazlauskas A. Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy? Prog Retin Eye Res 2014; 40C:16-34. PubMed
  • Lei H, Kazlauskas A. A reactive oxygen species-mediated, self-perpetuating loop persistently activates platelet-derived growth factor receptor 留. Mol Cell Biol 2013; 34:110-22. PubMed
  • Ruan GX, Kazlauskas A. Lactate engages receptor tyrosine kinases Axl, Tie2, and vascular endothelial growth factor receptor 2 to activate phosphoinositide 3-kinase/Akt and promote angiogenesis. J Biol Chem 2013; 288:21161-72. PubMed
  • Ruan GX, Kazlauskas A. VEGF-A engages at least three tyrosine kinases to activate PI3K/Akt. Cell Cycle 2012; 11:2047-8. PubMed
  • Lei H, Velez G, Kazlauskas A. Pathological signaling via PDGFR{alpha} involves chronic activation of Akt and suppression of p53. Mol Cell Biol 2011. PubMed
  • Russell MR, Liu Q, Lei H, Kazlauskas A, Fatatis A. The alpha-receptor for platelet-derived growth factor confers bone-metastatic potential to prostate cancer cells by ligand- and dimerization-independent mechanisms. Cancer Res 2010; 70:4195-203. PubMed
  • Im E, Motiejunaite R, Aranda J, Park EY, Federico L, Kim TI, Clair T, Stracke ML, Smyth S, Kazlauskas A. PLC{gamma} activation drives increased production of autotaxin in endothelial cells and LPA-dependent regression. Mol Cell Biol 2010; 30:2401-10. PubMed
  • Lei H, Rheaume MA, Kazlauskas A. Recent developments in our understanding of how platelet-derived growth factor (PDGF) and its receptors contribute to proliferative vitreoretinopathy. Exp Eye Res 2010; 90:376-81. PubMed
  • Lei H, Kazlauskas A. Focus on Molecules: Platelet-derived growth factor C, PDGF-C. Exp Eye Res 2007; 86:711-2. PubMed
  • Romeo GR, Kazlauskas A. Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. J Biol Chem 2008; 283:9595-605. PubMed
  • Motiejunaite R, Kazlauskas A. Pericytes and ocular diseases. Exp Eye Res 2007; 86:171-7. PubMed
  • Lei H, Velez G, Hovland P, Hirose T, Kazlauskas A. Plasmin is the major protease responsible for processing PDGF-C in the vitreous of patients with proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 2008; 49:42-8. PubMed
  • Im E, Kazlauskas A. Src family kinases promote vessel stability by antagonizing the Rho/ROCK pathway. J Biol Chem 2007; 282:29122-9. PubMed
  • Barcia RN, Dana MR, Kazlauskas A. Corneal graft rejection is accompanied by apoptosis of the endothelium and is prevented by gene therapy with bcl-xL. Am J Transplant 2007; 7:2082-9. PubMed
  • Romeo GR, Moulton KS, Kazlauskas A. Attenuated expression of profilin-1 confers protection from atherosclerosis in the LDL receptor null mouse. Circ Res 2007; 101:357-67. PubMed
  • Im E, Kazlauskas A. PtdIns-4,5-P2 as a potential therapeutic target for pathologic angiogenesis. Expert Opin Ther Targets 2007; 11:443-51. PubMed
  • Im E, Kazlauskas A. New insights regarding vessel regression. Cell Cycle 2006; 5:2057-9. PubMed
  • Im E, Kazlauskas A. Regulating angiogenesis at the level of PtdIns-4,5-P2. EMBO J 2006; 25:2075-82. PubMed
  • Kazlauskas A. The priming/completion paradigm to explain growth factor-dependent cell cycle progression. Growth Factors 2005; 23:203-10. PubMed
  • Im E, Venkatakrishnan A, Kazlauskas A. Cathepsin B regulates the intrinsic angiogenic threshold of endothelial cells. Mol Biol Cell 2005; 16:3488-500. PubMed
  • Tallquist M, Kazlauskas A. PDGF signaling in cells and mice. Cytokine Growth Factor Rev 2004; 15:205-13. PubMed
  • Jones SM, Kazlauskas A. Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nat Cell Biol 2001; 3:165-72. PubMed
  • Jones SM, Kazlauskas A. Connecting signaling and cell cycle progression in growth factor-stimulated cells. Oncogene 2000; 19:5558-67. PubMed
  • Balciunaite E, Jones S, Toker A, Kazlauskas A. PDGF initiates two distinct phases of protein kinase C activity that make unequal contributions to the G0 to S transition. Curr Biol 2000; 10:261-7. PubMed
  • Fambrough D, McClure K, Kazlauskas A, Lander ES. Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Cell 1999; 97:727-41. PubMed
  • Jones SM, Klinghoffer R, Prestwich GD, Toker A, Kazlauskas A. PDGF induces an early and a late wave of PI 3-kinase activity, and only the late wave is required for progression through G1. Curr Biol 1999; 9:512-21. PubMed
  • DeMali KA, Whiteford CC, Ulug ET, Kazlauskas A. Platelet-derived growth factor-dependent cellular transformation requires either phospholipase Cgamma or phosphatidylinositol 3 kinase. J Biol Chem 1997; 272:9011-8. PubMed
  • Franke TF, Yang SI, Chan TO, Datta K, Kazlauskas A, Morrison DK, Kaplan DR, Tsichlis PN. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 1995; 81:727-36. PubMed
  • Valius M, Secrist JP, Kazlauskas A. The GTPase-activating protein of Ras suppresses platelet-derived growth factor beta receptor signaling by silencing phospholipase C-gamma 1. Mol Cell Biol 1995; 15:3058-71. PubMed
  • Chung J, Grammer TC, Lemon KP, Kazlauskas A, Blenis J. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature 1994; 370:71-5. PubMed
  • Joly M, Kazlauskas A, Fay FS, Corvera S. Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding sites. Science 1994; 263:684-7. PubMed
  • Kazlauskas A, Feng GS, Pawson T, Valius M. The 64-kDa protein that associates with the platelet-derived growth factor receptor beta subunit via Tyr-1009 is the SH2-containing phosphotyrosine phosphatase Syp. Proc Natl Acad Sci U S A 1993; 90:6939-43. PubMed
  • Valius M, Kazlauskas A. Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal. Cell 1993; 73:321-34. PubMed
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