Kory J. Lavine, M.D., Ph.D.

Assistant Professor
Internal Medicine
Cardiovascular Medicine
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Immunology Program
Molecular Cell Biology Program

  • 314 362-1171

  • 314 362-0222

  • 314 362-0186

  • 8086

  • CSRB-NT 821 and 823

  • klavine@wustl.edu

  • https://klavine2.wixsite.com/lavinelab/our-research

  • heart failure, heart development, macrophages, innate immunity

  • Identify signaling pathways that mediate cardiac tissue repair/regeneration and heart failure pathogenesis.

Research Abstract:

Heart failure is a complex pathological process is that is initiated by an index event that injures the heart. Examples include myocardial infarction, viral infection, exposure to chemotherapy, or genetic cardiomyopathies. Outside of coronary revascularization for ischemic heart disease, no therapies yet exist to reverse the primary causes of heart failure. Patients diagnosed with heart failure receive a combination of medications that target a processed referred to as adverse remodeling, which results in progressive cardiomyocyte loss, fibrosis, hypertrophy, and dilation of the heart. Despite these interventions, the majority (>80%) of patients undergo disease progression and develop advanced heart failure. However, a minority of patients (<20%) will experience recovery of cardiac function and reversal of their disease. While these observations suggest that it is possible to repair the failing heart, little is known regarding the mechanisms that dictate whether a patient will recover or experience disease progression. The primary focus of our laboratory is identify new treatments that reverse the primary causes of heart failure and improve the heart`s intrinsic ability to undergo tissue repair. Despite modern practices, heart failure remains an important cause of morbidity and mortality worldwide. To tackle these challenging issues we have focused our efforts on two poorly understood areas with limited available therapies.

Precision Therapies for Heart Failure
For patients with dilated cardiomyopathies, little is known regarding precise mechanisms by which genetic variants result in heart failure and by what extent these mechanisms may vary between different genetic etiologies. To approach this problem and define precision therapeutics for dilated cardiomyopathy, we utilize Zebrafish and Mouse models in conjunction with advanced imaging and high throughput chemical screening platforms.

Immune Cell Heterogeneity and Ontogeny
Independent of the cause of heart failure (ischemic or non-ischemic), once patients develop heart failure, the majority of individuals will experience disease progression and eventually progress to end-stage disease. However, a small number of patients will experience disease remission and may spontaneously recover cardiac function. While these observations suggest that it is possible to recover a failing heart, surprisingly little is known regarding why individual patients display these divergent responses to cardiac injury. To define the mechanisms that dictate whether a patient will experience disease progression or recover from heart failure, we have focused on understanding how the innate immune system influences the heart’s response to acute and chronic tissue injury. Through these studies we have discovered that the heart contains a diverse and heterogeneous complement of immune cells derived from divergent embryonic origins with unique reparative and inflammatory functions. Current projects in the laboratory are focused on understanding the exact origins of these cells in the mouse and human heart, identifying molecular determinants of cell fate, and deciphering mechanisms by which each cell type is mobilized, activated and mediates its effector functions during development, disease, and regeneration.

Selected Publications:

Heart-resident CCR2+ macrophages promote neutrophil extravasation through TLR9-MyD88-CXCL5 signaling.
Li W, Hsiao H, Higashikubo R, Saunders B, Bharat A, Goldstein D, Krupnick A, Gelman A, Lavine KJ*, Kreisel D*. *Co-senior authors
Journal of Clinical Investigation: Insight. 2016; 1(12): e87315.

Primitive embryonic macrophages are required for coronary development and maturation.
Leid JM, Carrelha J, Boukarabila H, Epelman S, Jacobsen SE, Lavine KJ.
Circulation Research. 2016; 118(10):1498-511.

Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart.
Lavine KJ, Epelman S, Uchida K, Weber KJ, Nichols CG, Schilling JD, Ornitz DM, Randolph GJ, Mann DL.
Proceedings of the National Academy of Sciences of the United States of America. 2014; 111(45):16029-34.

Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation.
Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA, Calderon B, Brija T, Gautier EL, Ivanov S, Satpathy AT, Schilling JD, Schwendener R, Sergin I, Razani B, Forsberg EC, Yokoyama WM, Unanue ER, Colonna M, Randolph GJ, Mann DL.
Immunity. 2014; 40(1):91-104.

Origin and functions of tissue macrophages.
Epelman S, Lavine KJ, Randolph GJ.
Immunity. 2014; 41(1):21-35.

Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice.
Lavine KJ, Smith CS, Ornitz DM.
Journal of Clinical Investigation. 2008: 118(7): 2404-14.

Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development.
Lavine KJ, White AC, Park C, Smith CS, Choi K, Long F, Hui C, Ornitz DM.
Genes and Development. 2006; 20(12): 1651-66.

Endocardial and epicardial derived FGF signals regulate myocardial proliferation and differentiation in vivo.
Lavine KJ, Yu K, White AC, Zhang X, Smith C, Partanen J, Ornitz DM.
Developmental Cell. 2005; 8(1): 85-95.

Last Updated: 7/14/2017 10:10:11 AM

Composite of laboratory generated images
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