Bradlee Heckmann

Bradlee Heckmann
USF Health Byrd Alzheimer's Institute · Department of Molecular Medicine

PhD - Mayo Clinic College of Medicine

About

25
Publications
3,817
Reads
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1,408
Citations
Introduction
Bradlee Heckmann's current research interests focus on the contribution of canonical and non-canonical autophagy in the development, homeostatic maintenance, and disease pathology of the central nervous system. Areas of investigation include the modulation of neuroinflammation as a therapeutic approach to treating Alzheimer's Disease as well as the manipulation of the autophagic pathway in the tumor microenvironment for the putative treatment of pediatric glioblastomas including high-grade astrocytomas.
Additional affiliations
September 2020 - present
USF Health Byrd Alzheimer's Institute
Position
  • Professor (Assistant)
September 2016 - September 2020
St. Jude Children's Research Hospital
Position
  • Fellow
July 2011 - August 2016
Mayo Foundation for Medical Education and Research
Position
  • PhD Student
Education
July 2012 - August 2016
Mayo Clinic College of Medicine
Field of study
  • Biochemistry & Molecular Biology - Cancer Biology Program
August 2006 - May 2011
University of Kentucky
Field of study
  • Biology & Chemical Engineering

Publications

Publications (25)
Article
Full-text available
Noncanonical functions of autophagy proteins have been implicated in neurodegenerative conditions, including Alzheimer’s disease (AD). The WD domain of the autophagy protein Atg16L is dispensable for canonical autophagy but required for its noncanonical functions. Two-year-old mice lacking this domain presented with robust β-amyloid (Aβ) pathology,...
Article
Cell death pathways regulate various homeostatic processes. Autoimmune lymphoproliferative syndrome (ALPS) in humans and lymphoproliferative (LPR) disease in mice result from abrogated CD95-induced apoptosis. Because caspase-8 mediates CD95 signaling, we applied genetic approaches to dissect the roles of caspase-8 in cell death and inflammation. He...
Article
Multiple modes of cell death have been identified, each with a unique function and each induced in a setting-dependent manner. As billions of cells die during mammalian embryogenesis and daily in adult organisms, clearing dead cells and associated cellular debris is important in physiology. In this Review, we present an overview of the phagocytosis...
Article
The expression of some proteins in the autophagy pathway declines with age, which may impact neurodegeneration in diseases, including Alzheimer's Disease. We have identified a novel non-canonical function of several autophagy proteins in the conjugation of LC3 to Rab5+, clathrin+ endosomes containing β-amyloid in a process of LC3-associated endocyt...
Article
Administration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to glucocorticoid‐induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, ov...
Article
Classically, canonical autophagy has been considered a survival mechanism initiated in response to nutrient insufficiency. We now understand that autophagy functions in multiple scenarios where it is necessary to maintain homeostasis. Recent evidence has established that a variety of non-canonical functions for autophagy proteins are mechanisticall...
Article
G0/G1 switch gene 2 (G0S2) is a specific inhibitor of adipose triglyceride lipase (ATGL), the rate-limiting enzyme for intracellular lipolysis. Recent studies show that G0S2 plays a critical role in promoting triacylglycerol (TG) accumulation in the liver, and its encoding gene is a direct target of a major lipogenic transcription factor liver X re...
Article
Programmed cell death plays a central role in maintaining homeostasis. Various studies have demonstrated that programmed cell death is not a one‐way street; cells can survive even when the core cell death processes are underway. Cell death initiation, prevention, and recovery function in a coordinated fashion to establish and maintain a homeostatic...
Article
Programmed cell death (PCD) plays critical roles in development, homeostasis, and both control and progression of a plethora of diseases, including cancer and neurodegenerative pathologies. Besides classical apoptosis, several different forms of PCD have now been recognized, including necroptosis. The way a cell dies determines the reaction of the...
Article
LC3-associated phagocytosis (LAP) is a novel form of non-canonical autophagy where LC3 (microtubule-associated protein 1A/1B-light chain 3) is conjugated to phagosome membranes using a portion of the canonical autophagy machinery. The impact of LAP to immune regulation is best characterized in professional phagocytes, in particular macrophages, whe...
Article
The discovery of adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) provided a major paradigm shift in the understanding of intracellular lipolysis in both adipocytes and nonadipocyte cells. The subsequent discovery of G0/G1 switch gene 2 (G0S2) as a potent endogenous inhibitor of ATGL revealed a uniq...
Article
Liver X receptors (LXRs) are transcription factors essential for cholesterol homeostasis and lipogenesis. LXRα has been implicated in regulating hepatic triglyceride (TG) accumulation upon both influx of adipose-derived fatty acids (FAs) during fasting and stimulation of de novo FA synthesis by chemical agonism of LXR. However, whether or not a con...
Article
Full-text available
Intracellular triglyceride (TG) hydrolysis or lipolysis is catalyzed by the key intracellular triglyceride hydrolase, adipose triglyceride lipase (ATGL). The G0/G1 Switch Gene 2 (G0S2) was recently identified as the major selective inhibitor of ATGL and its hydrolase function. Since G0S2 levels are dynamically linked and rapidly responsive to nutri...
Article
Fat specific protein 27 (FSP27) plays a pivotal role in controlling the formation of large lipid droplet and energy metabolism. The cellular levels of FSP27 are tightly regulated through the proteasomal ubiquitin-mediated degradation. However, the upstream signals that trigger FSP27 degradation and the underlying mechanism(s) have yet to be identif...
Article
Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, is long known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least ei...
Article
Full-text available
Biochemical and cell-based studies have identified the G0/G1 Switch Gene 2 (G0S2) as a selective inhibitor of the key intracellular triacylglycerol hydrolase, adipose triglyceride lipase (ATGL). To better understand the physiological role of G0S2, we constructed an adipose tissue-specific G0S2 transgenic mouse model. In comparison to wild type anim...
Article
Full-text available
Recent biochemical and cell-based studies identified G0/G1 switch gene 2 (G0S2) as an inhibitor of adipose triglyceride lipase (ATGL), a key mediator of intracellular TG mobilization. Here we show that upon fasting G0S2 protein expression exhibits an increase in liver and a decrease in adipose tissue. Global knockout of G0S2 in mice enhanced adipos...
Article
3T3-L1 adipocytes are widely used as a model system for studying hormone-stimulated lipolysis. However, these cells were limited in their utility for gain- and loss-of-function studies due to the low efficiency of their transfection with plasmid DNA or small interfering RNA (siRNA) oligos. In this chapter, we provide a review of two methods establi...
Article
Full-text available
Adipose triglyceride lipase (ATGL) is the key triacylglycerol hydrolase in adipocytes. The precise mechanisms by which ATGL action is regulated by lipid droplet (LD) coat proteins and responds to hormonal stimulation are incompletely defined. By combining usage of loss- and gain-of-function approaches, we sought to determine the respective roles of...
Article
The G0/G1 switch gene 2 (G0S2) was originally identified in blood mononuclear cells following induced cell cycle progression. Translation of G0S2 results in a small basic protein of 103 amino acids in size. It was initially believed that G0S2 mediates re-entry of cells from the G0 to G1 phase of the cell cycle. Recent studies have begun to reveal t...
Article
Full-text available
Insulin stimulates the mobilization of glucose transporter 4 (GLUT4) storage vesicles to the plasma membrane, resulting in an influx of glucose into target tissues such as muscle and fat. We present evidence that CLIP-associating protein 2 (CLASP2), a protein previously unassociated with insulin action, is responsive to insulin stimulation. Using m...
Article
BACKGROUND AND PURPOSE The class III PI3K inhibitor, 3-methyladenine (3-MA), is commonly used to selectively block autophagy. Recent findings suggest a strong relationship between autophagy and lipid turnover. Here, we explore the effect of 3-MA on adipocyte lipolysis. EXPERIMENTAL APPROACH Assays were performed in 3T3-L1 cells. Cells were treated...
Article
Full-text available
TNF-α potently stimulates basal lipolysis in adipocytes, which may contribute to hyperlipidemia and peripheral insulin resistance in obesity. Recent studies show that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) act sequentially in catalyzing the first two steps of adipose lipolysis in response to β-adrenergic stimulation....

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