- Renal Diseases and Glomerulopathies
- Genetic and Kidney Cyst Diseases
- Chronic Kidney Disease and Diabetes
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and disorders
- Endoplasmic Reticulum Stress and Disease
- Renal and related cancers
- Mitochondrial Function and Pathology
- interferon and immune responses
- Genetic Syndromes and Imprinting
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Genomics, phytochemicals, and oxidative stress
- Drug Transport and Resistance Mechanisms
- Dialysis and Renal Disease Management
- Diabetes and associated disorders
- Metabolism and Genetic Disorders
- Birth, Development, and Health
- Cancer, Lipids, and Metabolism
- Lipid metabolism and biosynthesis
- Viral Infections and Vectors
- Complement system in diseases
- Biomedical Research and Pathophysiology
University of Pennsylvania
2020-2025
Children's Hospital of Philadelphia
2024
University of Pittsburgh
2020-2024
Penn Center for AIDS Research
2024
Institute of Nutrition, Metabolism and Diabetes
2023
University of Hyderabad
2017-2022
California University of Pennsylvania
2021
Indian Institute of Science Bangalore
2015
The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic are poorly understood. We developed a model of regeneration by titrating ischemic injury dose. performed detailed biochemical histological analysis profiled transcriptomic changes at bulk single-cell level (> 110,000 cells) over time. Our highlights proximal tubule cells as key susceptible injury. Adaptive correlated with fatty acid oxidation oxidative phosphorylation. identify...
The increased production of derivatives molecular oxygen and nitrogen in the form reactive species (ROS) (RNS) lead to damage called oxidative stress. Under normal physiological conditions, ROS generation is tightly regulated different cells cellular compartments. Any disturbance balance between antioxidant leads In this article, we discuss sources (endogenous exogenous) mechanisms. We also focus on pathophysiological significance stress various cell types liver. Oxidative implicated...
Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we employed kidney-specific expression quantitative traits and single-nuclear open chromatin analysis to show that genetic variants linked dysfunction on chromosome 20 target acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2 knock-out mice, demonstrated their protection from fibrosis in multiple disease...
Abstract Glomerular podocytes are integral members of the glomerular filtration barrier in kidney and crucial for permselectivity. These highly differentiated cells vulnerable to an array noxious stimuli that prevail several diseases. Elevated circulating growth hormone (GH) levels associated with podocyte injury proteinuria diabetes. However, precise mechanism(s) by which excess GH elicits podocytopathy remains be elucidated. Previous studies have shown express receptor (GHR) induce Notch...
Genome-wide association studies (GWASs) have identified more than 1000 loci where genetic variants correlate with kidney function. However, the specific genes, cell types, and mechanisms influenced by these remain largely uncharted. Here, we glutathione-specific gamma–glutamylcyclotransferase 1 ( CHAC1 ) on chromosome 15 as affected GWAS analyzing human gene expression methylation information. Both RNA protein were expressed in loop of Henle region mouse kidneys, was higher patients carrying...
The glomerular filtration barrier (GFB) plays a critical role in ensuing protein free urine. integrity of the GFB is compromised during hypoxia that prevails extreme physiological conditions. However, mechanism by which permselectivity remains enigmatic. Rats exposed to showed decreased rate, podocyte foot-processes effacement, and proteinuria. Accumulation hypoxia-inducible factor-1α (HIF1α) podocytes resulted elevated expression zinc finger E-box binding homeobox 2 (ZEB2) E- P-cadherin. We...
Glomerular podocytes are the major components of renal filtration barrier, and altered podocyte permselectivity is a key event in pathogenesis proteinuric conditions. Clinical conditions such as ischemia sleep apnea extreme physiological high-altitude sickness presented with hypoxia associated significant proteinuria. Hypoxia considered an etiological factor progression acute injury. A sustained increase hypoxia-inducible 1α (HIF1α) adaptive stimulus to hypoxic Although temporal association...
Podocytes are specialized cells of the glomerulus and key component glomerular filtration apparatus (GFA). GFA regulates permselectivity ultrafiltration blood. The mechanism by which integrity is compromised manifest in proteinuria during ischemic stroke remains enigmatic. We investigated hypoxia-induced a middle cerebral artery occlusion (MCAO) model. Ischemic hypoxia resulted accumulation HIF1α podocytes that increased expression ZEB2 (Zinc finger E-box-binding homeobox 2). ZEB2, turn,...
Diabetes shortens the life expectancy by more than a decade, and excess mortality in diabetes is correlated with incidence of kidney disease. Diabetic disease (DKD) leading cause end-stage Macrophage accumulation predicts severity injury human biopsies experimental models DKD. However, mechanism underlying macrophage recruitment glomeruli unclear. Elevated plasma growth hormone (GH) levels type I acromegalic individuals impaired glomerular biology. In this study, we examined whether...
Abstract The proteins of Plasmodium , the malaria parasite, are strikingly rich in asparagine. depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway acid biosynthesis, but retains gene encoding asparagine synthetase (AS). Here we show that deletion AS berghei ( Pb ) delays asexual- liver-stage development with substantial reduction formation ookinetes, oocysts sporozoites mosquitoes. In absence synthesis, extracellular supports suboptimal survival...
Background and Aims Hepatic crisis is an emergent complication affecting patients with sickle cell disease (SCD); however, the molecular mechanism of hepatobiliary injury remains poorly understood. Using knock‐in humanized mouse model SCD patient blood, we sought to mechanistically characterize SCD‐associated hepato‐pathophysiology applying our recently developed quantitative liver intravital imaging, RNA sequence analysis, biochemical approaches. Approach Results mice manifested sinusoidal...
Emerging evidence indicates that proper mitochondrial dynamics are critical for adipocyte differentiation and functional thermogenic capacity. We found the fission protein dynamin-related 1 (DRP1, also known as DNML1) is highly expressed in brown adipose tissue compared to expression white tissue, these levels increase during differentiation. Our results reveal inhibition of DRP1 using mdivi-1 mitigates beige differentiation-associated biogenesis. essential induction early-phase adipogenic...
The activation of hypoxia-inducible factors (HIF)-1α and 2α in the liver is closely linked to progression fatty diseases. Prior studies indicated that disrupting hepatocyte HIF-2α attenuates diet-induced hepatic steatosis, subsequently decreasing fibrosis. However, direct role fibrosis has not been addressed. Hepatic expression was examined mouse model carbon tetrachloride (CCl
Background & AimsCompelling evidence shows that glucagon-like peptide-1 (GLP-1) has a profound effect in restoring normoglycemia type 2 diabetic patients by increasing pancreatic insulin secretion. Although L-cells are the primary source of circulating GLP-1, current therapies do not target to increase GLP-1 levels. Our study aimed determine molecular underpinnings secretion as an impetus identify new interventions endogenous L-cells.MethodsWe used genetic mouse models intestine-specific...