There are two alveolar epithelial cell types in lung. Type II and Type 1. Upon lung injury, Type II cells serve as progenitors and differentiate into type 1 cells to heal the tissue. Our lab had had recently identified a novel transitional cell state assumed by type 2 cells as they differentiate into type 1 cells during normal regeneration after lung injury. We want to understand whether the transitional cells are related with ineffectual type 1 cell differentiation which may cause critical regenerative defect in pulmonary fibrosis. We set out with the goal of investigating the molecular mechanism of physiological and pathological alveolar repair in mouse model.
Research Discipline(s): Life Sciences
Diabetes mellitus is a very serious metabolic disorder that is a result of insufficient insulin production, which leads to uncontrolled blood glucose levels. Insulin is a peptide hormone that has a natural tendency to misfold and possibly form aggregates. Mice and humans share very similar endocrine physiology, and mice are often used to study diabetes. However there are some slight differences that must be considered for any experiment. Humans have a single gene, INS, that encodes for insulin, whereas mice have two genes, INS1 and INS2. The presence of insulin produced from two different genes leads to minor discrepancies in common protein analytical techniques such as western blotting. There must be controls in place in order to determine between insulin coded by either the INS1 or INS2 gene. This project seeks to establish a breeding colony of mice that are missing both copies of either the INS1 or INS2 gene.
Diabetes affects about 463 million people worldwide. It can cause various complications that affect several organs in the body. Diabetes is a disease that can be caused by insufficient insulin production. Insulin is synthesized in pancreatic beta cells located in clusters called islets. The laboratory of Dr. Peter Arvan at the University of Michigan is interested in the role of protein misfolding, and quality control systems including unfolded protein response (UPR), and endoplasmic reticulum associated-protein degradation (ERAD) in the development of diabetes. The physiological and genetic similarities between mice and humans allow the use of transgenic mouse models for laboratory studies.
The migration phenomena of monarch butterflies (Danaus plexippus) are quite unique in comparison to many other migrating species. Recent population decline in monarchs requires a strong understanding of their physiology and behavior. Monarchs represent different populations, e.g., migratory, and non-migratory. We are interested in the hormonal and genetic regulations of these phenotypes and behaviors. The juvenile hormone (JH) is a key factor in regulating the growth, physiology, and behavior of the insect. JH is the primitive and sub-social in insects with gonadotropin nature, whereas its functions in eusocial insects, has changed to regulate the division of labor and task assignment. The JH of monarch is gonadotropin primarily but also has other adult life functions, e.g., diapause.
Diabetes affects 27.8% of the US population. The disease alters the synthesis of insulin hormone that regulates glucose homeostasis. Pancreatic beta cells play a major role in the biosynthesis of insulin. There is a need to understand the biochemical pathway that permits the survivability of beta cells and their secretory pathway. Our laboratory studies how the misfolding of insulin precursor protein—“proinsulin” in beta cells affects insulin biosynthesis.
Via the article Colorectal cancer statistics, 2020, approximately 147,950 individuals were diagnosed with Colorectal Carcinoma (CRC) and 53,200 died from the disease in 2020. CRC, like many other cancers, activates signaling pathways to become more aggressive and deadly. STAT3 (signal transducer and activator of transcription) is a signaling pathway that promotes cell growth during normal development and cancer. The Shah lab has previously discovered that the STAT3 pathway plays a major role in promoting CRC growth. Interestingly, some CRC cell lines, like SW480 and HCT116, have high levels of p-STAT3 (a marker of STAT3 pathway activation) at baseline (without ligand stimulation). The Shah lab also found that glucose deprivation, but not the removal of amino acids or serum, decreased the activation of the STAT3 pathway in HCT116 and SW480 cells. We wanted to further explore the STAT3 signaling pathway in CRC cells and the interactions between signaling and metabolites in the CRC environment.
Mental illnesses such as depression and anxiety affect millions of Americans every year, and have been known to be related to stress exposure. To examine the link between the development of these disorders in mice and stress, prior research primarily examines the correlation between exposure to various stress paradigms, such as Chronic Social Defeat Stress (CSDS) and Chronic Unpredictable Stress (CUS), on various metrics collected shortly after exposure to these paradigms. Because the majority of this research has focused on acute impacts of stress exposure, however, there is a gap in the literature regarding the longitudinal effects of this stress in mice, which could help create a better model of how stress influences the development of mental disorders in clinical settings.
The APP (amyloid precursor protein) is particularly relevant in the investigation of neurodegenerative diseases, notably Alzheimer’s, as a result of rare mutations in APP protein coding gene. Quantifying cell mRNA levels is crucial to the determination of cell genomic status: mRNA is transcribed from cell DNA, and ultimately translated to cell proteins. In this project, we will administer the CRISPR/Cas9 complex in neuroblastoma cells, and confirm the alteration of APP gene expression.