- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Calcium signaling and nucleotide metabolism
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- DNA and Nucleic Acid Chemistry
- Diabetes and associated disorders
- Adipose Tissue and Metabolism
- Bacteriophages and microbial interactions
- Diffusion and Search Dynamics
- Genomics and Chromatin Dynamics
- RNA Interference and Gene Delivery
University of Michigan
2019-2025
University of California, Los Angeles
2017-2018
Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis has been linked type diabetes. Although many studies have attempted link ER T2DM, the specific effects of on function remain incompletely understood. To determine interrelationship between function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with...
Previous works have reported significant effects of macromolecular crowding on the structure and behavior biomolecules. The crowded intracellular environment, in contrast to vitro buffer solutions, likely imparts similar enzyme serving as gatekeeper for genome, RNA polymerase (RNAP), is among most regulated enzymes. Although it was previously demonstrated that affects association RNAP DNA, not much known about how acts late initiation promoter clearance steps, which are considered be...
The free calcium (Ca2+) levels in pancreatic beta cell organelles have been the subject of many recent investigations. Under pathophysiological conditions, disturbances these pools linked to altered intracellular communication and cellular dysfunction. To facilitate studies subcellular Ca2+ signaling cells and, particularly, between endoplasmic reticulum (ER) mitochondria, we designed a novel dual sensor which termed DS-1. DS-1 encodes two stoichiometrically fluorescent proteins within...
Mitochondrial damage is a hallmark of metabolic diseases, including diabetes, yet the consequences compromised mitochondria in tissues are often unclear. Here, we report that dysfunctional mitochondrial quality control engages retrograde (mitonuclear) signaling program impairs cellular identity and maturity β-cells, hepatocytes, brown adipocytes. Targeted deficiency throughout pathway, genome integrity, dynamics, or turnover, impaired oxidative phosphorylation machinery, activating...
Pancreatic beta cells maintain glucose homeostasis by secreting pulses of insulin in response to a rise plasma glucose. Pulsatile secretion occurs as result glucose-induced oscillations beta-cell cytosolic Ca2+. The endoplasmic reticulum (ER) helps regulate Ca2+, and ER stress can lead Ca2+ reduction, dysfunction, an increased risk type 2 diabetes. However, the mechanistic effects on individual calcium channels is not well understood. To determine tunicamycin-induced inositol...
ABSTRACT Mitochondrial damage is a hallmark of metabolic diseases, including diabetes and dysfunction-associated steatotic liver disease, yet the consequences impaired mitochondria in tissues are often unclear. Here, we report that dysfunctional mitochondrial quality control engages retrograde (mitonuclear) signaling program impairs cellular identity maturity across multiple tissues. Surprisingly, demonstrate defects machinery, which observe pancreatic β cells humans with type 2 diabetes,...
ABSTRACT Biological reactions in the cellular environment differ physicochemically from those performed dilute buffer solutions due to, part, slower diffusion of various components milieu, increase their chemical activities, and modulation binding affinities conformational stabilities. In vivo transcription is therefore expected to be strongly influenced by ‘crowdedness’ cell. Previous studies under macromolecular crowding conditions have focused mainly on multiple cycles RNAP-Promoter...
Abstract Pancreatic beta cells maintain glucose homeostasis by secreting pulses of insulin in response to a rise glucose. Pulsatile secretion occurs due glucose-induced oscillations beta-cell cytosolic Ca 2+ . The endoplasmic reticulum (ER) helps regulate , and ER stress can lead depletion, dysfunction an increased risk type 2 diabetes. To determine the effects tunicamycin-induced on inositol 1,4,5-triphosphate receptors (IP3Rs) ryanodine (RyRs) their involvement subsequent dysregulation,...