- Moravian College
- Lehigh University
Awards & Honors
- Student Chemistry Fellowship, Lehigh University (1984-1985)
- Byllesby Fellowship, Lehigh University (1985-1986)
- NIH Postdoctoral Fellowship (1987-1989)
- NIH Training Grant Award-Institutional (1990-1991)
- Allegheny-Singer Research Institute Pilot Project Grant (1996-1997)
- Pilot Project Award, Nathan Shock Centers of Excellence-NIA (1997-1998)
- W. W. Smith Charitable Trust (2001-2002)
- Cardiovascular Institute of Philadelphia (2002-2003)
Lisa Laury-Kleintop’s research focuses on the role that specific modifier proteins play in cardiovascular-associated diseases, including atherosclerosis and cardiac hypertrophy, and in autoimmune disorders. 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.
More Americans than ever are taking cholesterol-lowering drugs. Indeed, for those between the ages of 40 and 59, 17 percent take such medication, as do almost half of those aged 75 and older (48%), 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.
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 of developing cardiovascular disease.
Mediation of stress responses: Dr. Laury-Kleintop is investigating the role that 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.
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.
- Kaylend Manley, Biomedical Research Assistant
- Summer Sedano, Biomedical Research Assistant
- 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.
- Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth. Pestell TG, Jiao X, Kumar M, … Laury-Kleintop L, Pestell RG, et al. Oncotarget. 2017 Aug 4;8(47):81754-75.
- A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay Reichman M, Schabdach A, Kumar M, Zielinski T, Donover PS, Laury-Kleintop LD, Lowery RG. J Biomol Screen. 2015 Jul 20.
- 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.