A5090531694- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Cancer, Lipids, and Metabolism
- Liver Disease Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Lipid metabolism and biosynthesis
- Histone Deacetylase Inhibitors Research
- S100 Proteins and Annexins
- Antibiotics Pharmacokinetics and Efficacy
- Acute Myeloid Leukemia Research
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- Diet and metabolism studies
- Mesenchymal stem cell research
- Heat shock proteins research
- Fibroblast Growth Factor Research
- Immune Response and Inflammation
- Liver physiology and pathology
- Phagocytosis and Immune Regulation
- RNA and protein synthesis mechanisms
- Glycogen Storage Diseases and Myoclonus
- RNA Interference and Gene Delivery
University of Illinois Chicago
2018-2025
Kettering University
2024
Memorial Sloan Kettering Cancer Center
2024
University of Chicago
2021-2022
Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing human HCC tumorigenesis increases cell death, which cannot be restored GCK or mitochondrial binding deficient HK2. Upon silencing, glucose flux pyruvate lactate inhibited, but TCA...
Abstract Hexokinase 2 (HK2), which catalyzes the first committed step in glucose metabolism, is induced cancer cells. HK2’s role tumorigenesis has been attributed to its kinase activity. Here, we describe a independent HK2 activity, contributes metastasis. binds and sequesters glycogen synthase 3 (GSK3) acts as scaffold forming ternary complex with regulatory subunit of protein A (PRKAR1a) GSK3β facilitate phosphorylation inhibition by PKA. Thus, functions an A-kinase anchoring (AKAP)....
Abstract Liver cancer (LC) is the fourth leading cause of death from malignancies. Recently, a putative fifth hexokinase, hexokinase domain containing 1 (HKDC1), was shown to have significant overexpression in LC compared healthy liver tissue. Using combination vitro and vivo tools, we examined role HKDC1 development progression. Importantly, ablation stops progression via its action at mitochondria by promoting metabolic reprogramming shift glucose flux away TCA cycle. leads mitochondrial...
Glucokinase (GCK) is the principal hexokinase (HK) in liver, operating as a glucose sensor to regulate metabolism and lipid homeostasis. Recently, we proposed HK domain-containing 1 (HKDC1) be fifth with expression liver. Here, reveal HKDC1 have low glucose-phosphorylating ability demonstrate its association mitochondria hepatocytes. As shown previously that genetic deletion of leads altered hepatic triglyceride levels, also explored influence overexpression hepatocytes on cellular...
Highlights•AMPK activation is required to mitigate reactive oxygen species levels support metastasis•AMPK inhibits fatty acid synthesis (FAS) decrease NADPH consumption•AMPK supports oxidation (FAO) generate via malate conversion pyruvate•AMPK induces CD36 expression increase (FA) uptake and FAOSummaryAMPK's role in tumor initiation progression controversial. Here, we provide genetic evidence that AMPK for metastasis mouse models of breast cancer. In a model spontaneous cancer metastasis,...
The utility of a mid-cycle bone marrow biopsy (BMB) for early assessment response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there little consideration as to the possibility different dynamics among genetically defined subgroups. Clinical observations led hypothesis that AML and mutations IDH2-R172 (R172-m) exhibit particularly slow blast reduction following IC induction. purpose this study was analyze...
Hepatic steatosis is a major etiological factor in hepatocellular carcinoma (HCC), but factors causing lipid accumulation leading to HCC are not understood. We identify BNIP3 (a mitochondrial cargo receptor) as an suppressor that mitigates against attenuate tumor cell growth. Targeted deletion of
The receptor tyrosine kinase (RTK) pathway plays an essential role in development and disease by controlling cell proliferation differentiation. Here, we profile the Drosophila larval brain single RNA-sequencing identify Amalgam (Ama), encoding a adhesion protein of immunoglobulin IgLON family, that regulates RTK activity during glial development. Depletion Ama reduces proliferation, affects type composition disrupts blood-brain barrier (BBB) leads to hemocyte infiltration neuronal death. We...
S100B is frequently elevated in malignant melanoma. A regulatory mechanism was uncovered here which lowers mRNA and secreted protein levels of interleukin-6 (IL6) inhibits an autocrine loop whereby IL6 activates STAT3 signaling. Our results showed that affects expression transcriptionally. shown to form a calcium-dependent complex with the p90 ribosomal S6 kinase (RSK), turn sequesters RSK into cytoplasm. Consistently, inhibition found restore phosphorylation nuclear located substrate, CREB,...
Abstract Hepatic steatosis is a major etiological factor in hepatocellular carcinoma (HCC). Work reported here identifies BNIP3 as suppressor of HCC that mitigates against lipid accumulation. Loss decreased tumor latency and increased burden mouse model HCC. This was associated with accumulation elevated cell growth. Conversely, exogenous levels reduced Mutant BNIP3W18A unable to promote mitophagy did not decrease growth defective at reducing levels. Growth suppression by mediated effects on...
SUMMARY Genetic manipulation of mammalian cells is instrumental to modern biomedical research but currently limited by poor capabilities sequentially controlling multiple manipulations in cells. Currently, either highly multiplexed can be delivered populations all at one time, or gene regulatory sequences engineered conditionally activate a few within individual Here, we provide proof-of-principle for new system enabling genetic executed as preprogrammed cascade events. The leverages the...
Abstract Hexokinase 2 (HK2), a glycolytic enzyme that catalyzes the first committed step in glucose metabolism, is markedly induced cancer cells. HK2’s role tumorigenesis has been attributed to its kinase activity. However, we uncovered novel kinase-independent HK2 activity, which promotes metastasis. We found binds and sequesters glycogen 3 (GSK3) acts as scaffold forming ternary complex with regulatory subunit of protein A (PRKAR1a) GSK3b facilitate phosphorylation by PKA, inhibit Thus,...
Hexokinase 2 (HK2), a glycolytic enzyme that catalyzes the first committed step in glucose metabolism, is markedly induced cancer cells. HK2’s role tumorigenesis has been attributed to its kinase activity. However, we uncovered novel kinase-independent HK2 activity, which promotes metastasis. We found binds and sequesters glycogen 3 (GSK3) acts as scaffold forming ternary complex with regulatory subunit of protein A (PRKAR1a) GSK3b facilitate phosphorylation by PKA, inhibit Thus, functions...
Abstract Hepatocellular carcinoma (HCC) is a leading cause of death from cancer malignancies. Recently, hexokinase domain containing 1 (HKDC1), was shown to have significant overexpression in HCC compared healthy tissue. Using vitro and vivo tools, we examined the role HKDC1 progression. Importantly, ablation stops progression by promoting metabolic reprogramming shifting glucose flux away TCA cycle. Next, leads mitochondrial dysfunction resulting less cellular energy which cannot be...