Lisa Laury-Kleintop, PhD

Headshot of Lisa Laury-Kleintop, PhD

Resident Faculty

Associate Professor

Dr. Laury-Kleintop has more than 20 years of experience in molecular biology and in developing antibody-based assays. She studies how cells respond to stress signals, an interest that has helped bring a new understanding to the development of cardiovascular, autoimmune, ocular and kidney diseases, as well as therapeutic approaches for these disorders.

About

  • Chief Scientific Officer, Biological Therapeutics
  • 1999-Present: Associate Professor, Lankenau Institute for Medical Research

Research Descriptions

Background

Lisa Laury-Kleintop’s research focuses on the role that specific modifier proteins play in cardiovascular-associated diseases such as atherosclerosis and cardiac hypertrophy; autoimmune disorders such as rheumatoid arthritis and lupus; ocular diseases such as macular degeneration and diabetic retinopathy; and chronic kidney disease. She is working not only to understand the mechanism of action for these molecules, but also to devise new therapies that could benefit millions of disease sufferers.

Cardiovascular disease

More Americans than ever are taking cholesterol-lowering drugs. Indeed, among those ages 40 to 59, 17 percent take such medication, as do almost half of those aged 75 and older, according to the U.S. Centers for Disease Control and Prevention.

RhoB: Of the medications that lower cholesterol, statins are the most commonly prescribed. Statins limit vascular tissue damage following heart attacks and during atherosclerotic plaque formation. Dr. Laury-Kleintop is exploring how RhoB, a small GTPase altered by statins, modifies cell signaling events. She demonstrated that loss of RhoB function reduces the stress responses of vascular smooth muscle cells that mediate plaque formation in atherosclerosis. Her ongoing work focuses on RhoB as a potential drug target, and she is part of a team that has patented an antibody against RhoB.

Bin1: Despite preventative and therapeutic treatment strategies to reduce cardiovascular disease, abnormal alterations of the heart tissue can ultimately lead to heart failure. Work coordinated by Dr. Laury-Kleintop has demonstrated the role of a protein called Bin1 in the negative remodeling that leads to heart failure in preclinical models. Specifically, loss of Bin1 expression in cardiac myocytes leads to dilated cardiomyopathy with reduced cardiac function. Current work focuses on therapeutic approaches to reverse the negative remodeling, thus restoring heart function.

Autoimmune disease

The National Institutes of Health estimates that approximately 23.5 million Americans suffer with symptoms due to an autoimmune disease, such as type 1 diabetes mellitus, rheumatoid arthritis and lupus. These individuals also have an increased risk for developing cardiovascular disease.

Mediation of stress responses: Dr. Laury-Kleintop is investigating the role the RhoB protein plays in driving inflammatory signals leading to autoantibody-mediated autoimmune diseases. The team discovered that a RhoB-targeted biomolecule reduces autoantibody levels in preclinical models of rheumatoid arthritis and lupus. The results point to a potential therapy not only for rheumatoid arthritis and lupus but also for other autoantibody-mediated autoimmune diseases, such as diabetes and myasthenia gravis. Current efforts focus on preclinical validation in autoimmune disease models; development of other targeted therapeutics; and defining the role of this protein in immune system cells, with the goal of advancing this novel therapeutic approach into clinical practice.

Ocular disorders

About 11 million Americans suffer from age-related macular degeneration (AMD), and the number of vision-threatening cases of diabetic retinopathy (DR) is expected to reach 56 million worldwide by 2030, according to the BrightFocus Foundation.

Dr. Laury-Kleintop and her team demonstrated the potential benefit of blocking RhoB’s actions in these and other ocular disorders. Their antibody against RhoB inhibits the development of abnormal blood vessels that lead to the loss of vision by compromising the retina or more specifically, the central portion of the retina called the macula, critical for central-focused vision and commonly seen in wet AMD.

Kidney disease

Approximately 37 million U.S. adults have chronic kidney disease — and nine out of 10 don’t know they have it, according to the U.S. Centers for Disease Control and Prevention.

Dr. Laury-Kleintop and her collaborators devised a diagnostic reagent that can be covalently linked to a detectable label or immobilized to a substrate for the identification and quantitation of a portion of the RhoB protein.

This method enables the detection or measurement in the urine sample (or from a protein profile generated from a biologic sample) of RhoB protein or peptide fragments. Comparing and monitoring the level of RhoB protein or peptide in a patient’s urine or blood sample may enable the diagnosis of kidney diseases, or the identification of risk for developing those disorders. It may also enable clinicians to monitor the progression or remission of kidney diseases.

Collaborations within LIMR

In collaboration with Drs. George Prendergast, Laura Mandik-Nayak and Alex Muller, Dr. Laury-Kleintop has developed antibodies against tryptophan catabolism, immunomodulatory enzymes, IDO1 and IDO2. The antibodies targeting IDO1 and 2 were developed to characterize expression patterns of IDO enzymes in preclinical disease models and as potential therapeutic tools to affect the immune response.

Lab Personnel

  • Kaylend Manley, Biomedical Research Assistant
  • Summer Sedano, Biomedical Research Assistant

Publications

  • IDO1 Signaling Through GCN2 in a Subpopulation of Gr-1+ Cells Shifts the IFNγ/IL6 Balance to Promote Neovascularization. Dey S, Mondal A, DuHadaway JB, Sutanto-Ward E, Laury-Kleintop LD, Thomas S, Prendergast GC, Mandik-Nayak L, Muller AJ. Cancer Immunol Res. 2021 May;9(5):514-528.
  • Reliable detection of indoleamine 2,3 dioxygenase-1 in murine cells and tissues. Thomas S, Laury-Kleintop L, Prendergast GC. Methods Enzymol. 2019;629:219-33.
  • Preclinical study of the long-range safety and anti-inflammatory effects of high-dose oral meglumine. Manley K, Bravo-Nuevo A, Minton AR, Sedano S, Marcy A, Reichman M, Tobia A, Artlett CM, Gilmour SK, Laury-Kleintop LD, Prendergast GC. J Cell Biochem. 2019 Feb 27.
  • Reduction of the expression of the late-onset Alzheimer's disease (AD) risk-factor BIN1 does not affect amyloid pathology in an AD mouse model. Andrew RJ, De Rossi P, … Laury-Kleintop L, et al. J Biol Chem. 2019 Jan 28. doi: 10.1074/jbc.RA118.006379.
  • RhoB antibody alters retinal vascularization in models of murine retinopathy. Almonte-Baldonado R, Bravo-Nuevo A, Gerald D, Benjamin LE, Prendergast GC, Laury-Kleintop LD. J Cell Biochem. 2018 Dec 9. doi: 10.1002/jcb.28213.
  • Inflammatory Reprogramming with IDO1 Inhibitors: Turning Immunologically Unresponsive 'Cold' Tumors 'Hot'. Prendergast GC, Mondal A, Dey S, Laury-Kleintop LD, Muller AJ. Trends Cancer. 2018 Jan;4(1):38-58.
  • Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis. Merlo LM, Grabler S, DuHadaway JB, Pigott E, Manley K, Prendergast GC, Laury-Kleintop LD, Mandik-Nayak L. Clin Immunol. 2017 Feb 20;179:8-16.
  • RhoB blockade selectively inhibits autoantibody production in autoimmune models of rheumatoid arthritis and lupus. Mandik-Nayak L, DuHadaway JB, Mulgrew J, Pigott E, Manley K, Sedano S, Prendergast GC, Laury-Kleintop LD. Dis Model Mech. 2017 Sep 7.
  • Cardiac-Specific Disruption of Bin1 in Mice Enables a Model of Stress- and Age-Associated Dilated Cardiomyopathy. Laury-Kleintop LD, … Muller AJ, Prendergast GC, et al. J Cell Biochem. 2015 Nov;116(11):2541-51.
  • Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer. Prendergast GC, Smith C, Thomas S, Mandik-Nayak L, Laury-Kleintop L, Metz R, Muller AJ. Cancer Immunol Immunother. 2014 Jul;63(7):721-35.
  • Meglumine exerts protective effects against features of metabolic syndrome and type II diabetes. Bravo-Nuevo A, Marcy A, Huang M, Kappler F, Mulgrew J, Laury-Kleintop L, Reichman M, Tobia A, Prendergast GC. PLoS One. 2014 Feb 27;9(2):e90031
  • The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells. Trabanelli S, Očadlíková D, Ciciarello M, …  Laury-Kleintop L, Romero P, Prendergast GC, et al. J Immunol. 2014 Feb 1;192(3):1231-40.
  • Specific in situ detection of murine indoleamine 2, 3-dioxygenase. Thomas S, DuHadaway J, Prendergast GC, Laury-Kleintop L. J Cell Biochem. 2014 Feb;115(2):391-6.

Education and Training

Education

  • BS, Biology
    Moravian College
  • PhD, Biochemistry
    Lehigh University

Academic Titles

  • Chief Scientific Officer, Biological Therapeutics
  • 1999-Present: Associate Professor, Lankenau Institute for Medical Research