COBRE Research Project #1, Dr. Mira Han, Project PI
Integrated Prediction of Tissue of Origin in Cancers of Unknown Primary
Dr. Han is investigating Cancers of Unknown Primary (CUPs), which are cancers that are found at a metastatic stage, but without a primary site. Knowing the primary site for CUPs is important, because it can direct the therapies in cases where there are primary site-specific therapies available. Since DNA methylation is tissue-specific and change with cell differentiation, methylation sites are good markers for identifying tissue of origins. This project aims to find the methylation markers that are useful for tissue identification, and to develop the bioinformatics pipeline that enables primary site prediction. Using the markers and the pipeline developed, we will be able to better predict primary sites for CUPs.
COBRE Research Project #2, Dr. Qing Wu, Project PI
Developing the Genetics-Enhanced Model to Derive Personalized Reference Ranges for Bone Density
Dr. Wu’s research will increase the accuracy of osteoporosis diagnosis by using individualized clinical reference ranges based on individual genetic makeup and environment. With human life expectancy increasing, osteoporotic fracture is becoming a major public health issue. The purpose of this project is to create a genomics-enhanced method for generating personalized reference ranges of bone mineral density for diagnosing osteoporosis. This innovative approach is expected to be much more accurate at predicting osteoporotic fractures than existing methods, and is likely to greatly contribute to the diagnosis, prevention, and cure of osteoporosis. This approach is expected to be much more accurate at predicting osteoporotic fractures than existing methods, and is likely to greatly contribute to the diagnosis, prevention, and cure of osteoporosis.
COBRE Research Project #3, Dr. Jingchun Chen, Project PI
Schizophrenia and Autoimmune Disorders: The Role of Microglial Cells
Dr. Chen is investigating the functional role of microglia and immune system dysfunction in schizophrenia etiology to help identify new genetic markers for subtyping schizophrenia and to develop new therapeutic strategies. Studies have shown that there is a strong association between schizophrenia, autoimmune disorders, and inflammation. A large body of evidence also shows that immune cells, like microglia in the brain, are the major mediators in the development of schizophrenia. Here, we are studying the genetic relationship between schizophrenia and autoimmune disorders. We will also investigate the role of microglia in schizophrenia. The research has a great potential to elucidate the role of the immune system in some schizophrenia subgroup, and help to discover novel molecular biomarkers for diagnosis, and effective targets for the personalized schizophrenia treatment.
COBRE Research Project #4, Dr. Nora Caberoy, Project PI
Phagocytosis of Amyloid Beta
Dr. Caberoy is researching the buildup of harmful amyloid beta protein that aggregates in the Alzheimer’s brain. Normally, amyloid betas are removed by specialized cells in the brain called microglia. However, the removal of these aggregates leads to activation of the inflammatory pathway that eventually results in death of the brain cells. A long-term goal is to develop novel therapeutic strategy for clearing deleterious metabolic products to prevent Alzheimer’s disease. Alzheimer’s is a progressive, neurodegenerative disease that is poorly understood and has no cure, existing treatments only address some psychological and behavioral symptoms. Thus, effective pharmacological intervention for prevention and treatment are essential. This project investigates the role of engineered hybrid proteins in the clearance of amyloid beta and to test their potential for therapy to prevent progression of Alzheimer’s disease in an animal model.
COBRE Research Project #5, Dr. Qian "Chris" Liu, Project PI.
Identification of novel methylation biomarkers in schizophrenia
Alzheimer's disease (AD) is an incurable disease without effective medicine. Genetic variants alone could not interpret the etiology of AD, and DNA methylations have been identified to be linked with AD. However, traditional methods have technical limitations to reliably generate whole-genome methylation profiles, creating barriers to investigate the role of DNA methylations in AD. In this project, we will combine the latest Nanopore sequencing techniques and deep learning algorithms to accurately detect genome-wide DNA methylations as well as genomic variants. We will then identify methylation-variant joint biomarkers in AD by comparing AD patients and unaffected controls. This project is expected to uncover novel methylations and methylation-variant biomarkers to deepen our understanding of AD etiology.
COBRE Research Project #6, Dr. Prasun Guha, Project PI.
Role of IPMK in generation of small intestinal carcinoid
Dr. Guha's lab is focused on unraveling the role of higher-order inositol phosphate (HOIP) signaling in disease pathology. Recent findings from the lab suggest that disruptions in HOIP signaling impact intestinal health. Mutations affecting the function of IPMK (Inositol polyphosphate multikinase), a key enzyme in the HOIP pathway, have been linked to the development of human intestinal neuroendocrine tumors and inflammatory bowel disease (IBD). However, the precise mechanisms by which IPMK influences intestinal health and how its loss of function contributes to disease remain unclear.
To address this gap in understanding, Dr. Guha's lab is employing a combination of chemical, genetic, and next-generation sequencing approaches. By investigating the biological functions of IPMK at the epigenetic, transcriptional, and cellular signaling levels, the lab aims to uncover the underlying mechanisms driving intestinal pathologies. The outcomes of these studies are anticipated to advance fundamental scientific knowledge and hold significant translational potential for developing novel therapeutic strategies.