Louise Hecker
Associate Professor, BIO5 Institute
Associate Professor, Clinical Translational Sciences
Associate Professor, Medicine
Primary Department
Department Affiliations
(520) 626-2855
Work Summary
Louise Hecker’s research is focused on understanding why the process of regenerative biology and mechanisms of tissue injury-repair "goes awry" in aging. She is working to identifying novel pathways that can be targeted to reverse age-associated diseases, such as Idiopathic pulmonary fibrosis (IPF).
Research Interest
Dr. Hecker's research background and training are rooted in regenerative biology and investigating mechanisms of tissue injury-repair. Regenerative biology studies the molecular and cellular processes by which tissues and organs renew or repair themselves. However, the normal healing and repair process becomes less efficient as we age. Dr. Hecker’s research is focused on understanding why this process "goes awry" in aging and identifying novel pathways that can be targeted to reverse age-associated diseases, such as Idiopathic pulmonary fibrosis (IPF). Research by Dr. Hecker and her colleagues at UAB identified a novel role for NADPH oxidase-4, or Nox4, an oxidant-generating enzyme that plays a critical role in the formation of scar tissue (fibrosis) in the lung (results were published in Nature Medicine in 2009). Dr. Hecker’s ongoing research involves discovering new drug candidates to target Nox4 and preclinical testing of novel therapies aimed to treat IPF. She is founder and chief scientific officer of Regenerative Solutions, LLC, a contract research organization that provides highly specialized preclinical testing services for biotechnology and pharmaceutical companies with drug development platforms in pulmonary fibrosis. She is principal investigator on a study, “Aging, Fibroblast Senescence, and Apoptosis in Lung Fibrosis,” funded through June 2017 by a nearly $1 million grant from the Department of Veterans Affairs (1 IK2 BX001477-01A1).

Publications

Hecker, L., Garcia, J. G., Wang, T., Colson, B., Knox, A., Mohamed, M., Quijada, H., Desai, A., Ahmad, K., Shin, Y. J., & Palumbo, S. (2017). Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury. American journal of physiology. Lung cellular and molecular physiology, 312(3), L297-L308.
BIO5 Collaborators
Joe GN Garcia, Louise Hecker

Acute respiratory distress syndrome (ARDS) is a devastating critical illness disproportionately affecting the elderly population, with both higher incidence and mortality. The integrity of the lung endothelial cell (EC) monolayer is critical for preservation of lung function. However, mechanisms mediating EC barrier regulation in the context of aging remain unclear. We assessed the severity of acute lung injury (ALI) in young (2 mo) and aged (18 mo) mice using a two-hit preclinical model. Compared with young cohorts, aged mice exhibited increased ALI severity, with greater vascular permeability characterized by elevated albumin influx and levels of bronchoalveolar lavage (BAL) cells (neutrophils) and protein. Aged/injured mice also demonstrated elevated levels of reactive oxygen species (ROS) in the BAL, which was associated with upregulation of the ROS-generating enzyme, Nox4. We evaluated the role of aging in human lung EC barrier regulation utilizing a cellular model of replicative senescence. Senescent EC populations were defined by increases in β-galactosidase activity and p16 levels. In response to lipopolysaccharide (LPS) challenge, senescent ECs demonstrate exacerbated permeability responses compared with control "young" ECs. LPS challenge led to a rapid induction of Nox4 expression in both control and senescent ECs, which was posttranslationally mediated via the proteasome/ubiquitin system. However, senescent ECs demonstrated deficient Nox4 ubiquitination, resulting in sustained expression of Nox4 and alterations in cellular redox homeostasis. Pharmacological inhibition of Nox4 in senescent ECs reduced LPS-induced alterations in permeability. These studies provide insight into the roles of Nox4/senescence in EC barrier responses and offer a mechanistic link to the increased incidence and mortality of ARDS associated with aging.

Hecker, L., & Birla, R. K. (2008). Intangible factors leading to success in research: strategy, innovation and leadership. Journal of cardiovascular translational research, 1(1), 85-92.

At the heart of research is the scientific process, which includes identifying a knowledge gap, execution of experiments, and finally, presentation of scientific data. Identifying a systematic way to undertake research is important; however, equally important are intangible factors, including strategy, innovation and leadership, in determining the outcome of any research project. These intangible factors, although often unspoken, are the essence of success in research. Strategy determines the direction of research and the ability to respond to acute changes in the field to ensure a competitive advantage. Innovation involves generating novel ideas, and at the heart of innovation is the ability to create a positive work environment. Leadership is the ability to exercise influence so as to create change; empowerment and the ability to create leaders at every level are central to effective leadership. Collectively, defining and implementing aspects of these intangible factors will strengthen any research endeavor.

Wang, T., Mathew, B., Wu, X., Shimizu, Y., Rizzo, A. N., Dudek, S. M., Weichselbaum, R. R., Jacobson, J. R., Hecker, L., & Garcia, J. G. (2016). Nonmuscle myosin light chain kinase activity modulates radiation-induced lung injury. Pulmonary circulation, 6(2), 234-9.

Radiotherapy as a primary treatment for thoracic malignancies induces deleterious effects, such as acute or subacute radiation-induced lung injury (RILI). Although the molecular etiology of RILI is controversial and likely multifactorial, a potentially important cellular target is the lung endothelial cytoskeleton that regulates paracellular gap formation and the influx of macromolecules and fluid to the alveolar space. Here we investigate the central role of a key endothelial cytoskeletal regulatory protein, the nonmuscle isoform of myosin light chain kinase (nmMLCK), in an established murine RILI model. Our results indicate that thoracic irradiation significantly augmented nmMLCK protein expression and enzymatic activity in murine lungs. Furthermore, genetically engineered mice harboring a deletion of the nmMLCK gene (nmMLCK(-/-) mice) exhibited protection from RILI, as assessed by attenuated vascular leakage and leukocyte infiltration. In addition, irradiated wild-type mice treated with two distinct MLCK enzymatic inhibitors, ML-7 and PIK (peptide inhibitor of kinase), also demonstrated attenuated RILI. Taken together, these data suggests a key role for nmMLCK in vascular barrier regulation in RILI and warrants further examination of RILI strategies that target nmMLCK.

Joseph, B., Khalil, M., Hashmi, A., Hecker, L., Kulvatunyou, N., Tang, A., Friese, R. S., & Rhee, P. (2017). Survival benefits of remote ischemic conditioning in sepsis. The Journal of surgical research, 213, 131-137.

Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model.

Hecker, L., Madison, D., Dapson, R., & Holzherr, V. (2003). Presence of modified serous glands in the caudal integument of the red-backed salamander (Plethodon cinereus). Journal of Herpetology, 732-736.