Student Directory

Natalie Choi, 2nd Year Master's Student; PI - Dr. Masato Yoshizawa

Juliette Doumergue, 2nd Year Ph.D. Student; PI – Dr. Xin Chen

Cholangiocarcinoma (CCA) is an aggressive form of liver cancer that threatens the lives of many. By understanding the pathogenesis of a transforming tumor cell in CCA models, new targeted therapy treatments can be developed for this and other forms of liver cancer. Our research project observes the transcription factor TEAD2, which plays a role in regulating cell proliferation based on its interaction with the YAP/TAZ pathway. We are reproducing an experiment that showed deleting TEAD2 decreases tumor growth in HCC models and applying it to CCA models. We have generated sgRNA sequence against mouse TEAD2, and cloned it into H138 lentiviral vector as well as pX330 expression vector. We plan to delete TEAD2 in mouse CCA cell lines and co-inject sgTEAD2/pX330 into CCA mice models. Tumor sizes will then be compared to controlled sgEGFP injected CCA models. Knowing which TEAD isoform is a major contributor to tumor growth is essential to developing TEAD isoform inhibitors. This research can lead to future drug developments that impact tumor growth.

Rachael Downham, 3rd Year Ph.D. Student; PIs – Dr. Olivier Le Saux, Dr. Edwin Kamau

Campylobacteriosis is a microbial gastrointestinal infection caused by Campylobacter bacteria that affects the general population. From 2012 to 2022, Campylobacter was noted to have the highest incidence rate for foodborne disease in the United States with Hawai’i having the highest incidence. Campylobacteriosis is one of the primary causes of ‘Traveler’s Diarrhea’. In severe cases, post-infection sequelae such as irritable bowel syndrome (IBS), reactive arthritis (RA), Guillain Barre Syndrome (GBS), and even various forms of gastrointestinal cancer can occur. Even though Campylobacteriosis continues to be one of the most common diseases worldwide, antimicrobial drug resistance is growing and there is no prophylactic vaccine. Indeed, genetic variation of antigenic targets poses significant challenges for vaccine development. Advanced genetic characterization from collected specimens using whole genome sequencing (WGS) analysis will provide foundational knowledge that can be used to elucidate bacterial phylogeny, antimicrobial resistance profiling, possible vaccine targets and even cancer markers. A comprehensive insight into the genetics of various infectious strains of Campylobacter and their respective pathogenic mechanisms will help predict disease severity enabling surveillance of new Campylobacter strains and intervention.

Kayla Hallam, 4th Year Ph.D. Student; PI – Dr. Lucia Seale

Thermogenic adipocytes (brown and beige fat cells) play a crucial role in regulating energy expenditure and metabolic health. My project investigates the degradation and recycling of selenoproteins, specifically glutathione peroxidases (GPXs), in thermogenic adipocytes. The study aims to determine how the enzyme selenocysteine lyase (Scly) interacts with the proteasomal machinery to recycle selenium (Se) from degraded GPXs, sustaining their levels to protect cells from oxidative stress. By identifying ubiquitinated lysine residues in GPXs and using gene knockout models to assess Scly’s role, the research seeks to clarify the molecular mechanisms involved. The findings could lead to improved strategies for managing obesity by enhancing energy expenditure and antioxidant defenses in adipocytes.

Publications

Min Seok Han, 4th Year Ph.D. Student; PI –Dr. Jesse Owens

Current genome editing technologies suffer from several drawbacks such as safety and limited efficiency that prevent their utilization across a potentially wider range of possible treatment avenues. Enzymes such as transposases, as well as DNA-binding proteins such as zinc fingers have potential to be used for gene therapy applications. Our research focuses on using bacterial directed evolution systems to engineer these proteins to integrate large gene cargos at high efficiencies and specificities towards defined target sites at various human genomic loci. We have adapted a system called substrate-linked protein evolution (SLiPE) to evolve the piggyBac (pB) transposase. We are also exploring directed evolution systems to evolve designer zinc fingers. In the future, we plan to generate novel protein variants with improved properties and adapt various directed evolution systems to engineer a myriad of proteins that are relevant to genome editing.

Diana Hawkins-Westergard, 3rd Year Ph.D. Student; PIs – Dr. Jason Lee, Dr. Naoto Ueno

Triple-negative breast cancer (TNBC) is an aggressive form of the disease, representing 15-20% of all breast cancer cases. While chemotherapy remains a common and effective treatment, high recurrence rates and limited treatment options pose significant challenges. Our research aims to address these clinical needs by exploring new treatment strategies for patients whose cancer has become resistant to drugs like PARP inhibitors. We are currently investigating the mechanisms behind this resistance, with a focus on identifying molecules that, when targeted, could help overcome drug resistance and improve the effectiveness of PARP inhibitors. By exploring cellular pathways, such as the DNA repair pathway, we hope to uncover new treatment possibilities and advance the field of translational cancer research for patients with TNBC.

Jonathan Haynes, 2nd Year Master's Student; PI – Dr. Benjamin Green

Cancer immunotherapies are treatments that stimulate the immune system to fight against cancer. Our project focuses on how we can improve the efficacy of various immunotherapies against liver cancers for better clinical outcomes. We use animal models and flow cytometry to assess the anti-tumor capability of therapies such as checkpoint inhibitors and peptide vaccines and their effect on immune cell populations.

Kari Inda, 3rd Year Ph.D. student; PI - Joanne Yew

An organism remains biologically active even after death.  Genes are transcribed, proteins are synthesized, and lipids are metabolized for up to 96 hours.  Tissues from various organs have distinct patterns of activity and different rates of degradation, suggesting organ-specific responses rather than passive decay.  The phenomenon of postmortem gene expression has been shown to be conserved from silkworms to humans; however, how these programs are initiated and regulated are not well understood.  We aim to utilize the ultimate stressor—death—to unveil unexplored pathways of cell death and senescence, and to investigate different vulnerabilities of various tissues to decomposition using Drosophila and mouse models.  We will examine the roles of canonical senescence genes in postmortem processes through genetic knockdown and reporter assays in Drosophila.  Elucidating the dynamics of molecular and cellular changes postmortem may identify signals that initiate or predict senescence-related chronic diseases such as Alzheimer’s, diabetes, and cancer.  Postmortem molecular signatures may also serve as robust biomarkers for improving the accuracy of postmortem interval estimation.  Lastly, a deeper understanding of tissue-specific decay processes will improve organ preservation and transplantation for life-saving medical procedures.

April Iwatani, 2nd Year Master's Student; PI – Dr. Michael Ortega

Chronic kidney disease (CKD) is a major complication of Type 2 diabetes (T2DM). In Hawaii, it disproportionately affects Native Hawaiians and Pacific Islanders, who experience higher rates of kidney failure compared to other populations. Our research focuses on the role of chronic low-grade inflammation in diabetic kidney disease (DKD) by exploring the mechanistic relationship between hyperglycemia and NF-κB signaling. Specifically, we aim to determine how non-canonical NF-κB activation drives inflammation and the progression of renal fibrosis. Using advanced techniques such as single-cell RNA sequencing, spatial transcriptomics, and knockout mouse models, we have found that impaired autophagy increases non-canonical NF-κB activity through elevated levels of the cytokine TWEAK and, TNF superfamily receptor, Fn14. This research endeavors to inform the development of novel therapies targeting non-canonical NF-κB signaling to mitigate chronic inflammation and fibrosis thereby addressing progressive loss of kidney function in diabetic patients.

Cady Komori, 3rd Year Ph.D. Student; PI – Dr. Kathryn Schunke

My research focuses on understanding the cell fate decision of heart mesenchymal cell progenitors and the associated signaling and transcriptional pathways. Single nuclei sequencing of mesenchymal progenitors at different stages will provide insight into the transcriptional control that guides cell fate and specification. Through immunohistochemistry and lineage tracing, I am mapping epicardial eptithelial to mesenchymal transition to elucidate cell fate determination spatially and temporally. Additionally, identifying how the tumor suppressor/fibroblast transcription factor, Tcf21, directs gene transcription will provide insights into how this transcription factor functions in cancer-associated fibroblasts. This work is critical for understanding heart architecture and function and has significant implications for heart disease and fibrosis.

Michelle Nagata, 3rd Year Ph.D. Student; PI – Dr. Brenda Hernandez

Squamous cell carcinoma (SCC) is a rare histology for rectal cancer but the most common histology for anal cancer, which is predominantly caused by high-risk human papillomavirus (HPV) infection. Although rectal SCC is rare, there is a rising incidence of early-onset rectal cancers in the United States and other populations globally. An increased risk of rectal SCC has been observed in immunocompromised populations, including people living with human immunodeficiency virus (HIV), who also have an increased risk of anal SCC due to persistent HPV infection. The etiology and pathogenesis of rectal SCC are not understood; therefore, investigating the mechanisms contributing to the development of rectal SCC could inform strategies for prevention, screening, diagnosis, and treatment, especially for high-risk populations. Our research investigates the potential etiologic role of HPV infection in rectal SCC. We will examine de-identified clinical and pathologic data from cancer registries and evaluate archival tumor samples using immunohistochemistry and molecular assays to explore the mechanistic role of HPV, the tumor microenvironment, and other biomarkers in squamous metaplasia and rectal SCC development, aiming to identify pathways for intervention.

Publications

Luke Nelson, 6th Year Ph.D. Student; PI – Dr. Noemi Polgar

Upon exercise, skeletal muscle releases extracellular vesicles (EVs) that benefit the metabolism of recipient tissues. Our goal is to understand the biological components driving EV secretion of skeletal muscle (SkM) in response to increased Ca2+ flux. We are using live-cell imaging, nano-particle counting, electron microscopy, and mass spectrometry to understand the mechanism underlying EV biogenesis and secretion in SkM. We have found that the exocyst complex associates with EV precursor vesicles and specific Rab GTPases to perform targeted secretion of EVs upon stimulation with exercise mimetic. These studies highlight how EVs can serve as the mediators of the beneficial effects of exercise. Discovery of this mechanism will also provide a model for how other contractile cells, including cardiomyocytes, may release small EVs to promote “long-range” communication.

Publications

Jessica Nicholson, 5th Year Ph.D. Student; PI – Dr. Marla Berry

I am a doctoral researcher in Dr. Marla Berry’s lab studying the effects of stress hormones on antioxidant proteins in the brain. Chronic stress hormone exposure can cause many detrimental effects in the brain, which is highly susceptible to stress. Selenoproteins, produced from dietary selenium in cells, are important in the body for their antioxidant function. Therefore, we believe that chronic stress may affect the levels of important selenoproteins in the brain making it more prone to damage. This has implications in nutrition and could provide valuable insight into the importance of maintaining dietary selenium levels as a way to protect the brain from damage.

Anna Nilsson, 5th Year Ph.D. Student; PI – Dr. Kathryn Schunke

Cardiovascular disease is the leading cause of death in the diabetic population, with cardiomyopathy and cardiac autonomic dysfunction being common consequences of diabetes. Thus, targeting the heart specifically in the treatment of diabetes could lead to increased longevity in this vulnerable population. Our research uses a brain-heart axis to improve autonomic function in the heart and address features of diabetic cardiomyopathy like reduced contractile function. Using a rat model of diet-induced pre-diabetes and type 2 diabetes, we have found that activating brainstem cardiac vagal neurons is cardio-protective. In future experiments we aim to determine the mechanism of protection and identify therapeutic targets with translational potential.

Alice Pendergast, Student; PI - Benjamin Fogelgren

Connor Schuller, 4th Year Ph.D. Student; PI – Dr. Noemi Polgar

My research focuses on the role of intracellular trafficking in regulating cardiac muscle metabolism.

Bryan Suechting, 4th Year Ph.D. Student; PI – Dr. Alika Maunakea

Native Hawaiians and Pacific Islanders face disproportionate rates of chronic health conditions such as hypertension diabetes, and heart disease. One potential contributor to these variations is the shift from a traditional diet rich in poi, a probiotic fermented taro dish, to one dominated by rice and rich fatty foods. Historically, poi made up nearly 70% of Native Hawaiian daily caloric intake, and studies suggest it offers several health benefits, including promoting beneficial gut bacteria and anti-inflammatory responses. Our research explores how production methods and the environment impact the microbial fermentation profiles of poi, and how these profiles influence gut health and immune function. By combining metagenomics, ecological interaction studies, dietary intervention, and immune profiling, we aim to better understand how different fermentation processes shape gut microbiome composition and contribute to overall health. Our ultimate goal is to connect ʻāina to ola, bridging cultural tradition and medical insight to promote personal well-being and community health.

Christopher Tran, 5th Year Ph.D. Student; PI – Dr. Jesse Owens

Yongmiao Wang, 1st Year Ph.D. Student; PI - Dr. Youping Deng

My future research will focus on utilizing high-throughput DNA sequencing technologies to deeply investigate variations in the cancer genome, including somatic mutations, germline mutations, and copy number variations (CNVs), aiming to uncover the molecular mechanisms underlying cancer development and progression, and to provide a theoretical foundation for precision medicine. This research will enhance the understanding of cancer genomic variations and molecular mechanisms, offering new theoretical insights and technical approaches for the early diagnosis, precise treatment, and prognostic assessment of cancer, thereby holding significant scientific and clinical application value.

Marissa Watanabe, 3rd Year Ph.D. Student; PI – Dr. Matthew Pitts

Methylmercury (MeHg) is an environmental neurotoxin that readily crosses the blood-brain barrier and targets the central nervous system, with the main source of human exposure being fish consumption. Selenium (Se) is an essential trace element that is ingested through the diet and incorporated into selenoproteins in the form of the amino acid selenocysteine (Sec). Se supplementation within a narrow window optimizes selenoprotein function, including redox-regulating selenoproteins such as glutathione peroxidase (GPX) and thioredoxin reductase (TXNRD), which are critical for maintaining brain health. MeHg binds with high affinity to Se, thereby attenuating the antioxidant activity of GPX and TXNRD, leading to increased oxidative damage in the brain and contributing to the development of neuropsychiatric diseases. Oxidative damage in parvalbumin interneurons (PVIs), a subtype of GABAergic interneuron expressing the calcium-binding protein parvalbumin, disrupts their ability to coordinate principal neuron activity and subsequently decreases gamma oscillations that are critical for normal cognitive function and memory formation, contributing to schizophrenia (SCZ). PVIs are preferentially surrounded by perineuronal nets (PNNs), extracellular matrix structures that protect them from oxidative damage and stabilize synapses. The vulnerability of PVIs to oxidative insults highlights the importance of Se for healthy PVI and PNN function, as elevated exposure to ROS during adolescence has been shown to impair PVI and PNN development in animal models. Our research employs methods such as electrophysiology, cell culture, protein assays, confocal microscopy, behavioral assessments, and differential gene expression analysis to investigate how chronic, low-grade juvenile exposure to MeHg alters the maturation and functionality of PVIs and PNNs and how these changes contribute to the development of psychiatric disorders such as SCZ.

Karlin Wurlitzer, 2nd Year MS Student; PI - Dr. Matthew Pitts

Selenoprotein I (SELENOI) catalyzes the production of a key component of myelin, which protects and insulates neuronal axons. However, myelin-producing oligodendrocytes have high concentrations of iron. Iron is a vital metal cofactor due to its aptitude for redox reactions, but this propensity also predisposes it to generating reactive oxygen species (ROS) via Fenton reactions. In the brain, iron dysregulation in various cell types has been implicated in neurodegenerative disorders such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and hereditary spastic paraplegia (HSP). Our lab studies a brain-specific mouse knockout (KO) model to elucidate the effects of SELENOI on iron metabolism in order to understand how redox homeostasis might play a role in iron-dependent neurodegeneration.

Brennan Yamamoto, 5th Year Ph.D. Student; PI – Dr. Alika Maunakea

Environmental exposures, including diet, are known modulators of health and epigenetics. Understanding how the diet, and particularly the gut microbiome affects a person’s disease state is essential in developing personalized medicine. Through epigenetic and metagenomic analysis we have identified key relationships between the gut microbiome and DNA methylation in diabetic and non-diabetic people. Future aims of our research include expanding to understand the roles of exposure to toxins in human epigenetics, to further our understanding of DNA methylation regulation and its relationship to health status.

IASO: Precise genome editing idealizing backbone healing and tale-guided piggybac