A5069589993- Viral Infections and Vectors
- Occupational and environmental lung diseases
- Mitochondrial Function and Pathology
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- Cancer, Hypoxia, and Metabolism
- Neuroblastoma Research and Treatments
- Bone and Dental Protein Studies
- Fungal and yeast genetics research
- Immune cells in cancer
- Renal and related cancers
- Hearing, Cochlea, Tinnitus, Genetics
- Virus-based gene therapy research
- Vestibular and auditory disorders
- Olfactory and Sensory Function Studies
- Electron Spin Resonance Studies
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Animal Disease Management and Epidemiology
- Pleural and Pulmonary Diseases
- interferon and immune responses
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Research and Treatments
Meharry Medical College
2022-2024
Hypertension Institute
2022-2024
Vanderbilt University Medical Center
2009-2021
State Research Center of Virology and Biotechnology VECTOR
2001-2019
Centre for Research and Development
2018
UNC Lineberger Comprehensive Cancer Center
2018
Yale University
2012-2017
Federal Medical-Biological Agency
2016
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
2015
New York University
2007-2009
Kidney tubules use fatty acid oxidation (FAO) to support their high energetic requirements. Carnitine palmitoyltransferase 1A (CPT1A) is the rate-limiting enzyme for FAO, and it necessary transport long-chain acids into mitochondria. To define role of tubular CPT1A in aging injury, we generated mice with tubule-specific deletion Cpt1a (Cpt1aCKO mice), were either aged 2 years or injured by aristolochic unilateral ureteral obstruction. Surprisingly, Cpt1aCKO had no significant differences...
Abstract Pleural malignant mesothelioma (MM) is an aggressive cancer with a very long latency and short median survival. Little known about the genetic events that trigger MM their relation to poor outcome. The goal of our study was characterize major genomic gains losses associated origin progression assess clinical significance. We performed Representative Oligonucleotide Microarray Analysis (ROMA) on DNA isolated from tumors 22 patients who recurred at variable interval disease after...
Abstract Background We investigated the role of A2B-adenosine receptor in regulating immunosuppressive metabolic stress tumor microenvironment. Novel antagonist PBF-1129 was tested for antitumor activity mice and evaluated safety immunologic efficacy a phase I clinical trial patients with non-small cell lung cancer. Methods The antagonists their impact on immune microenvironment were lung, melanoma, colon, breast, epidermal growth factor receptor–inducible transgenic cancer models. Employing...
Fus1 has been established as mitochondrial tumor suppressor, immunomodulator, and antioxidant protein, but molecular mechanism of these activities remained to be identified. Based on putative calcium-binding myristoyl-binding domains that we identified in Fus1, explored our hypothesis regulates calcium handling calcium-coupled processes.Fus1 loss resulted reduced rate uptake calcium-loaded epithelial cells, splenocytes, activated CD4(+) T cells. The Fus1-deficient cells correlated with...
Acquired hearing loss is a worldwide epidemic that affects all ages. It multifactorial in etiology with poorly characterized molecular mechanisms. Mitochondria are critical components hearing. Here, we aimed to identify the mechanisms of mitochondria-dependent using Fus1 KO mice, our novel model mitochondrial dysfunction/oxidative stress.Using auditory brainstem responses (ABRs), mouse as novel, clinically relevant age-related (ARHL) metabolic etiology. We demonstrated early decline...
Acute and chronic kidney injuries induce increased cell cycle progression in renal tubules. While promotes repair after acute injury, the role of ongoing tubular disease is unknown. Two weeks initiation disease, we blocked at G1/S phase by using an FDA-approved, selective inhibitor CDK4/6. Blocking CDK4/6 improved function reduced injury fibrosis 2 murine models disease. However, deletion cyclin D1, which complexes with to promote progression, paradoxically injury. Expression quantitative...
Abstract Purpose: Tumor extracellular matrix (ECM) plays a crucial role in cancer progression mediating and transforming host-tumor interactions. Targeting the ECM is becoming an increasingly promising therapeutic approach treatment. We find that one of proteins, HAPLN1, overexpressed majority mesotheliomas. This study was designed to characterize protumorigenic HAPLN1 mesothelioma. Experimental Design: Overexpression assessed validated on large set normal/mesothelioma specimens RNA protein...
Insufficient advances in the development of effective therapeutic treatments sporadic Alzheimer's Disease (sAD) to date are largely due lack sAD-relevant animal models. While vast majority models do recapitulate AD's hallmarks plaques and tangles by virtue tau and/or beta amyloid overexpression, these not reflect fact that sAD (unlike familial AD) genes risk factors per se other mechanisms like oxidative stress, metabolic dysregulation inflammation play key roles AD etiology. Here we...
The habituation/cross-habituation test (HaXha) is a spontaneous odor discrimination task that has been used for many decades to evaluate olfactory function in animals. Animals are presented repeatedly with the same odorant after which new introduced. time animal explores object measured. An considered cross-habituate during novel stimulus trial when exploration higher than prior and indicates degree of patency. On other hand, habituation across repeated trials involves decreased related...
FUS1/TUSC2 is a novel tumor suppressor located in the critical 3p21.3 chromosomal region frequently deleted multiple cancers. We previously showed that Tusc2-deficient mice display complex immuno-inflammatory phenotype with predisposition to cancer. The goal of this study was analyze possible involvement TUSC2 malignant pleural mesothelioma (MPM) - an aggressive inflammatory cancer associated exposure asbestos. insufficiency clinical specimens MPM assessed via RT-PCR (mRNA level),...
Decreased energy production and increased oxidative stress are considered to be major contributors aging aging-associated pathologies. The role of mitochondrial calcium homeostasis has also been highlighted as an important factor affecting different pathological conditions. Here, we present evidence that loss a small protein Fus1 maintains results in premature aging, pathologies, decreased survival. We showed Fus1KO mice develop multiple early signs including lordokyphosis, lack vigor,...
The Wnt/β-catenin signaling pathway plays an important role in renal development and is reexpressed the injured kidney other organs. β-Catenin protective acute injury (AKI) through actions on proximal tubule, but current dogma that promotes fibrosis of chronic disease (CKD). As tubular β-catenin CKD remains unclear, we genetically stabilized (i.e., activated) specifically murine tubules. Mice with increased were protected 2 models AKI to progression. Oxidative stress, a common feature CKD,...
Fus1, encoded by a 3p21.3 tumour suppressor gene, is down-regulated, mutated or lost in the majority of inflammatory thoracic malignancies. The mitochondrial localization Fus1 stimulated us to investigate how modulates response and function mouse model asbestos-induced peritoneal inflammation. Asbestos treatment resulted decreased expression wild-type (WT) immune cells, suggesting that asbestos exposure may compromise Fus1-mediated response. Untreated Fus1(-/-) mice had an ~eight-fold higher...
ABSTRACT Fus1 is a tumor suppressor protein with recently described immunoregulatory functions. Although its role in sterile inflammation being elucidated, regulating immune responses to infectious agents has not been examined. We used here murine model of Acinetobacter baumannii pneumonia identify the antibacterial host defenses. found that loss mice results significantly increased resistance A. pneumonia. observed earlier and more robust recruitment neutrophils macrophages lungs infected...
FUS1/TUSC2 is a mitochondrial tumor suppressor with activity to regulate cellular oxidative stress by maintaining balanced ROS production and homeostasis. Fus1 expression inhibited ROS, suggesting that individuals high level of may have lower in normal tissues and, thus, be more prone stress-induced side effects cancer treatment, including radiotherapy. As the role modulation radiosensitivity unknown, we set out determine molecular mechanisms involvement IR response tissues. Mouse whole-body...