Student Research Fellowship Program
A mentored research program for our medical, dental and pharmacy students
Hope Ball, Ph.D.
Pediatric Cancer Research: Determining the Role of Cellular Metabolism in Therapeutic Resistance
Cancer is the second leading cause of death in the pediatric population. While adult cancers arise from genetic instability caused by repeated carcinogenic exposure, most pediatric cancers are caused by mutations or dysregulations in pathways governing normal development. Pediatric mutations are unique and demonstrate significant differences from their adult same-cancer counterparts. Because of this, findings from adult malignancies cannot be directly translated into effective pediatric therapies. While improvements in diagnostic and treatment strategies have improved patient outcomes, a significant number of cases are still compromised by therapeutic resistance. Therapy development is hampered both by unique pediatric mutations and because the underlying mechanisms of therapy resistance remain poorly understood.
Marc Basson, M.D., Ph.D., M.P.H. – 1
Mechanistic Drivers of SLFN12-Mediated Chemotherapy Sensitization in Lung Adenocarcinoma
The Basson Lab has been investigating the role of SLFN12, an intermediate member of the Schlafen protein family, in the biology and drug responsiveness of several cancer types. Prior work from the laboratory showed that high SLFN12 expression is associated with improved prognosis and increased chemotherapy sensitivity in cancers such as triple-negative breast cancer. Our ongoing research in lung adenocarcinoma has demonstrated similar trends, where SLFN12 overexpression enhances sensitivity to specific cytotoxic drugs in some cell lines. However, other lung adenocarcinoma cell lines remain resistant or display only minimal changes in drug response despite SLFN12 overexpression. To understand these differences, we analyzed proteomic profiles from SLFN12-overexpressing sensitive and resistant lung adenocarcinoma cell lines. Several proteins were significantly upregulated in the sensitive line compared with the resistant line, while other proteins were downregulated in the sensitive cells but elevated in the resistant ones. These findings suggest that downstream effectors of SLFN12 may determine whether a cell line becomes sensitized or remains resistant. We are generating stable lentiviral cell lines that either overexpress SLFN12 or contain an empty vector control in one sensitive and one resistant lung adenocarcinoma model. The proposed project will manipulate proteins identified from proteomic analysis by knocking down proteins that are upregulated in the sensitive line and overexpressing proteins that are downregulated. The goal is to determine whether altering these targets can convert sensitive lines into resistant ones and, conversely, make resistant lines more sensitive to chemotherapy.
Marc Basson, M.D., Ph.D., M.P.H. – 2
SLFN12 sensitizes Colorectal cancer to certain chemotherapy drugs
The Basson Lab has been investigating the effects of SLFN12, an intermediate protein of the Schlafen family linked to better prognosis in aggressive and resistant cancer types, such as triple-negative breast cancer and lung adenocarcinoma. The Basson lab published an article showing that the improved prognosis observed in triple-negative breast cancer cells with high SLFN12 expression is attributed not only to the tumor’s intrinsic biology when SLFN12 is expressed, but also to the sensitization of certain chemotherapy drugs. Our work on lung adenocarcinoma, which is still ongoing, confirmed this. In colon cancer, high levels of SLFN12 expression are often linked to a better prognosis, implying that elevated SLFN12 could be a positive outcome indicator, possibly because it helps suppress tumor cell growth and promotes differentiation. We look forward to testing how different chemotherapy drugs affect the cell viability of HT-29 and HCT 116, two colon adenocarcinoma cell lines, when we overexpress SLFN12, compared to the baseline SLFN12 expression in the same cell lines.
Yeong-Renn Chen, Ph.D.
CB-839 Targets Cardiac Mitochondrial Glutaminolysis to Mitigate Acute Myocardial Injury
The objective of this research project is to investigate how mitochondrial health influences cardiac adaptation to acute myocardial injury, with a long-term goal of reducing the progression to heart failure. Using a murine model of ischemia–reperfusion (I/R) injury, we will examine the role of mitochondrial glutaminase (GLS1), a key enzyme mediating glutamine oxidation (glutaminolysis), which may compromise myocardial resilience under pathological stress.
Lisa Cooper, Ph.D.
Neuron counts in the unusually large brains of whales
Within mammals, dolphins and beluga whales are known to have a large brain size relative to body size. However, little is known of the composition of these brains. To increase our understanding of the different cells that make up the brains of terrestrial vs. marine mammals, this study aims to establish a fundamental understanding of the number of neurons in the brains of an echolocating and agile beluga whale compared to a slow move and non-echolocating bowhead whale. This study will use fluorescent labels to stain the neurons in the brains of both animals. Numbers of neurons will be counted using a confocal microscope. We hypothesize that the cerebellum of both animals will be roughly equal in their neuron density, but the cortex of the beluga brain will display a greater neuron density. Results will be compared with published accounts of neuron densities within terrestrial mammals (i.e., bats, elephants, carnivores, and ungulates). We expect our results will add a critical understanding of the architecture of big brains in cetaceans as well as elucidate the evolution of brains within aquatic and terrestrial mammals.
Feng Dong, Ph.D.
Molecular and Cellular Mechanisms Driving the Development of Aortic Stenosis
Previously, we identified a blunted stromal cell–derived factor-1 (SDF-1)/CXCR4 signaling axis in diabetes, and our preliminary data indicate that chronic CXCR4 expression is increased in cardiac myocytes from diabetic mice. Although CXCR4 activation in the diabetic heart produces a pronounced negative inotropic effect, we believe this seemingly counterintuitive response represents a key adaptive mechanism. Importantly, our initial studies show that diabetic mice (high-fat, high-sugar diet) lacking CXCR4 specifically in cardiac myocytes exhibit markedly higher mortality than diet-matched wild-type controls. More recently, using our endothelial cell–specific CXCR4 knockout mice, we discovered that loss of CXCR4 in endothelial cells leads to the development of aortic stenosis. This proposal builds on these novel models of CXCR4 deficiency to investigate the role of CXCR4 in aortic valve stenosis and to define the mechanisms by which CXCR4 loss disrupts endothelial and cardiac function.
Jessica Ferrell, Ph.D. – 1
TGR5 and FGF21 in Altered Sugar Preference and Associated Metabolic Outcomes
Takeda G protein-coupled receptor 1 (TGR5) is a receptor activated by bile-acids endogenously, known for its anti-diabetic and anti-inflammatory properties. TGR5 is expressed in the liver, intestine, and brain and represents a potential therapeutic target for obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD). Tgr5-/- mice have significantly increased expression of fibroblast growth factor 21 (FGF21) upon administration of alcohol. These mice may also have altered leptin and adiponectin signaling from brain. FGF21 is a liver-produced hormone that is induced by carbohydrate consumption 9including ethanol and sugar), which negatively feeds back to the brain to suppress of carbohydrate consumption. We previously demonstrated that voluntary alcohol consumption is reduced in Tgr5-/- mice, possibly due to highly elevated FGF21. The aim of this study is to determine if FGF21 is upregulated in Tgr5-/- mice exposed to voluntary drinking of sucrose-water, if it will contribute to a reduction in their sweet-taste preference through canonical FGF21 signaling.
Jessica Ferrell, Ph.D. – 2
The Effects of Lactobacillus murinus Supernatant on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disease that begins with steatosis and can develop into metabolic dysfunction-associated steatohepatitis (MASH), hepatic cirrhosis, or hepatocellular carcinoma. The involvement of various metabolic and inflammatory pathways in MASLD suggests that exploring a range of interventions targeting different aspects of the disease is necessary. Probiotics, including live bacteria or the bacterial culture supernatant that contain metabolites, have been proposed to have alleviating effects on the progression of MASLD, primarily by improving liver enzymes, gut microbiome modulation, and reducing inflammation and oxidative stress. Growing evidence suggests that bacterial metabolites, in the form of supernatants and other bacterial extracts, have immunomodulatory properties and are considered safer than live probiotics. Lactobacillus murinus (L. murinus) is a gram-positive bile acid hydrolase bacterium with the ability to reduce the transport of bacterial products and reduce markers of systemic inflammation in mice. However, the mechanisms by which this occurs, and the metabolites L. murinus produces to exert these effects, are largely unknown. Here, we will determine if administering L. murinus supernatant can modify the progression of diet-induced MASLD in mice.
Alex Galazyuk, Ph.D.
Neuron counts in the unusually large brains of whales
Age-related hearing loss remains one of the most common chronic conditions of aging. It begins from the gradual loss or impairment of the inner and outer hair cells in the cochlea. This loss leads to the development of deficits in the central auditory system which eventually cause difficulties in processing temporally complex sounds such as speech, especially in noisy environments. Typically, individuals experience a notable decline in their hearing abilities after the age of 65, whereas cochlea degradation begins much earlier in life. Within the field, there exists a consensus that central plasticity, often referred to as central gain enhancement, serves as a compensatory mechanism to counterbalance the loss of input from the cochlea to the central auditory system due to aging. The postsynaptic mechanism underlying this compensation is largely unknown. It has been hypothesized that alterations in the balance between excitation and inhibition may play the key role. The goal of this project is to elucidate the postsynaptic mechanisms that contribute to the central gain and to identify pharmacological therapy to improve hearing performance in aged individuals.
Adam Goodwill, Ph.D., FCVS – 1
GLP 1 Mediated Cardioprotection During Anthracycline Exposure in a Large Animal Physiology Model
Anthracycline chemotherapy is highly effective in cancer treatment, but cumulative exposure produces predictable cardiac injury. The early stages of toxicity involve shifts in oxygen handling, impaired mitochondrial efficiency, and progressive mechanical dysfunction that ultimately progress to heart failure. Therapies that reduce metabolic stress and preserve contractile mechanics may allow greater cumulative dosing without cardiac collapse.
GLP 1 receptor agonists have shown clear cardiovascular benefit in clinical populations. Several groups have reported improved mitochondrial efficiency, improved ATP linked respiration, reduced lipid oxidation and reduced apoptotic signaling with GLP 1 treatment. Retrospective human data also suggest a reduction in heart failure events of roughly fifty percent when GLP 1 therapy is present during anthracycline exposure. These findings indicate that GLP 1 may offset mitochondrial stress, protect the microvasculature, and maintain contractile reserve under toxic load.
This study will quantify cardioprotection using NEOMEDs large animal model. The student will evaluate myocardial oxygen consumption and metabolic efficiency, measure coronary flow reserve, and analyze pressure volume loops for early divergence of contractile mechanics. Results are expected to define an integrated physiological profile that indicates whether GLP 1 slows deterioration or permits higher safe dosing thresholds.
Adam Goodwill, Ph.D., FCVS – 2
Ischemia Dependent Cardioprotection by SGLT2 Inhibitors Mechanistic and Metabolomic Evaluation in a Large Animal Preparation
SGLT2 inhibitors reduce heart failure events across many clinical populations, and this benefit cannot be explained by glucose lowering or canonical endocrine signaling pathways. Our laboratory has established that cardioprotection by SGLT2 inhibitors is strictly dependent on the presence of myocardial ischemia. In a large animal model, we previously demonstrated that the improvement in diastolic relaxation, quantified by the time constant tau, scales with the severity of ischemia. Protection was observed with both canagliflozin and empagliflozin which indicates a class mediated effect rather than a compound specific artifact.
Our group has also developed and published an extracorporeal coronary perfusion preparation in open chest swine that maintains a fully beating, load bearing heart while allowing servo controlled perfusion of the LAD across a wide hemodynamic range. In this model coronary pressure and flow are adjustable from approximately 140 to 40 mmHg and coronary venous sampling provides a direct index of oxygen delivery and extraction. This platform allows controlled induction of ischemia, continuous pressure volume monitoring, measurement of tau, and real time sampling of extracellular fluid from the myocardium.
The purpose of the 2026 student project is to determine whether SGLT2 mediated cardioprotection is driven by direct myocardial drug action or requires systemic signals. We will perform intracoronary infusions of SGLT2 inhibitor into ischemic and non ischemic territories while perfusion is varied across and beyond the autoregulatory range. During each condition we will record pressure volume relations, measure tau, quantify coronary flow, and collect extracellular and coronary venous samples for metabolomic and proteomic analysis in collaboration with Cedars Sinai Medical Center. By integrating physiologic response with biochemical signatures, this work will identify mechanistic pathways responsible for ischemia linked cardioprotection.
Neysa Grider-Potter, Ph.D.
Bat craniovertebral morphology across dietary regimes
The semicircular canals and vestibule sense angular and linear accelerations of the head and facilitate visual stability and whole-body coordination. Size, shape and orientation of these canals has long been associated with sensitivity to head motion and locomotor agility. As a clade, bats are among the most agile of mammals practicing astounding feats of aerial agility in order to capture flying prey. However, there is variation in locomotor capabilities within bats that tend to fall along dietary regimes with insectivorous species being more agile than their frugivorous relatives. Further, there is extreme variation in cervical morphology that is largely lack functional explanation. Because the cervical spine balances and moves the head, the stability requirements of the inner ear should influence vertebral morphology. The goal of this work is to understand how inner ear morphology varies among bats of diverse dietary habits and if inner ear morphology is, in turn, shaping the cervical spine.
Tobin Hieronymus, Ph.D.
Muscular and Fascial Instrumentation and Anatomy Using Reflected Light Polarimetry and Contrast-Enhanced MicroCT
Smooth muscle plays a critical role in the function of many organ systems, but our ability to understand the effects of smooth muscle contraction are limited by our current inability to directly record smooth muscle activity in-vivo. Unlike skeletal muscle, smooth muscle does not depend on cell-membrane depolarization to coordinate contraction, so standard techniques such as electromyography (EMG) will not work. Current research in Hieronymus lab is focused on two major aims: (1) developing new methods of measuring peripheral smooth muscle optical properties to record activity, and (2) developing selective, localized, and reversible interventions to manipulate smooth muscle contraction for functional studies. This summer research project has two available tracks: one track will prototype and test components of a direct polarimetric probe system with the aim of developing in vivo instrumentation; the other will make use of recent advances in microCT imaging to characterize the architecture of smooth muscle tissue in bird skin (our lab’s experimental model system for smooth muscle polarimetry and manipulation), with particular attention to its relationship to the superficial and deep fascia of the human-comparable musculoskeletal elements of the forelimb.
Louis Kwantwi, Ph.D.
Principal Investigator name, title and location where the research will take place
Acetaminophen (Tylenol) overdose causes liver injury when the drug is converted into a harmful metabolite that damages hepatocytes. This project uses a liver cell line to determine whether M64HCl can promote recovery after exposure to this toxic metabolite. By comparing cellular responses in injured cells treated with M64HCl versus untreated controls, the student will evaluate the compound’s potential protective or restorative effects. The project provides hands-on experience with cell-based injury models and introduces the student to how candidate compounds are assessed for therapeutic promise.
Guiming Liu, Ph.D.
Role of FAK in Human Urothelial Cell Migration and Proliferation
Ulcerative cystitis is a debilitating condition characterized by ulcerative lesions within the bladder lining, including Hunner-type interstitial cystitis (IC) and hemorrhagic chemical (cyclophosphamide, ifosfamide, or ketamine–induced) or radiation cystitis. Damage to the superficial urothelial layer exposes underlying tissues to urine, solutes, and toxins, triggering inflammation and hematuria. This results in significant pain and a spectrum of lower urinary tract symptoms (LUTS)—including frequency, urgency, incontinence, dysuria, suprapubic pain, hematuria, and incomplete bladder emptying—that severely impair quality of life. Although the incidence of ulcerative cystitis continues to rise, effective treatments remain limited.
Focal Adhesion Kinase (FAK) is a protein tyrosine kinase that functions as a scaffold linking the cytoskeleton to the extracellular matrix through focal adhesions. We have demonstrated that a newly developed FAK activator, M64HCl, accelerates mucosal healing in a rat model of acetic acid–induced intestinal injury (BMC Gastroenterol. 2025, 25:347). We hypothesize that M64HCl can be repurposed to address the critical unmet need in ulcerative cystitis by promoting urothelial repair through FAK activation. To test this hypothesis, we conducted a pilot in vivo study showing that subcutaneous administration of M64HCl before intraperitoneal cyclophosphamide (CYP) significantly reduced hemorrhage and urothelial denudation four days after CYP administration in mice. To translate these findings toward clinical application, our next step is to determine whether M64HCl increases p-FAK levels and enhances adhesion, migration, and proliferation in primary human bladder urothelial cells, as well as to elucidate its underlying molecular mechanisms. This will be the focus of the summer student fellow’s project. The student will culture primary human bladder urothelial cells, measure FAK and p-FAK expression, and assess cell adhesion, migration, and proliferation following FAK inhibition/gene knockdown or activation/gene overexpression. Additionally, gene expression profiles of focal adhesion and cytoskeletal regulators will be analyzed, and phosphoproteomic profiling will be performed to identify mechanistic pathways. Key target molecules will be further validated through gain- and loss-of-function experiments.
Priya Raman, Ph.D.
Role of smooth muscle O-GlcNAcylation in regulation of cognitive dysfunction in Type 2 diabetes
Type 2 diabetes (T2D) negatively impacts cerebrovascular function and increases the risk of developing Alzheimer’s disease-related dementia (ADRD). Growing literature supports the notion that dysregulated function of vascular smooth muscle cells (VSMC), a major cell type found in blood vessels that regulate cerebrovascular function, is a putative player in AD-related pathology and neurodegeneration. Hyperglycemia, a hallmark feature of T2D, increases O-GlcNAc transferase (OGT) signaling, a key regulator of protein O-GlcNAcylation. Increased O-GlcNAcylation, a ubiquitous posttranslational modification, correlates with adverse vascular remodeling and vascular dysfunction in T2D. However, it is unknown whether increased cerebrovascular O-GlcNAcylation contributes to cognitive dysfunction and AD pathology in T2D. The proposed project provides a unique platform to determine whether loss of VSMC-specific OGT-mediated O-GlcNAcylation inhibits cognitive dysfunction in T2D. For this, conditional VSMC-specific OGT knockout mice and wild-type controls (both sexes) on a high-fat high-sugar diet will be aged to 6 months, followed by a battery of behavioral tests to measure their cognitive, emotional, and sensorimotor behavior. The summer student working on this project will learn murine behavior phenotyping, including scoring of the behavioral tests, data analysis and data interpretation. The proposed studies will advance our understanding of how T2D contributes to cognitive dysfunction, with a focus on the regulatory role of cerebrovascular OGT-mediated O-GlcNAcylation, paving the way for the discovery of novel therapies to treat ADRD in diabetes.
Priya Raman, Ph.D. – 2
Crosstalk of Aging and Metabolic Syndrome in Atherosclerosis
Metabolic syndrome (MetS), a cluster of modifiable cardiovascular (CV) risk factors including hyperglycemia, visceral obesity, and dyslipidemia, significantly accelerates atherosclerosis, amplifying the risk of cardiovascular morbidity and mortality in older adults with MetS. Aging and MetS share overlapping pathogenic mechanisms that can synergistically accelerate atherosclerosis. Despite its clinical importance, the molecular mechanisms by which MetS drives age-related vasculopathy are incompletely understood. The proposed project is part of a larger research initiative to uncover novel molecular pathways and protein networks that drive accelerated atherosclerosis in MetS as a function of age. Using a mouse model of combined MetS and atherosclerosis developed in our lab, we will study the interaction of aging with MetS on atherosclerotic lesion formation. Specifically, MetS and non-MetS mice (both sexes) on standard laboratory diet will be aged to 6 months and 1 year, followed by animal harvests for collection of plasma, heart and aortic vessels. The summer student working on this project will perform histological staining of aortic root sections to assess the severity of atherosclerotic lesions in our mice genotypes, including data analysis and data interpretation. The student will also attain familiarity with the relevant scientific literature in the field.
Jeff Wenstrup, Ph.D.
Brain Circuitry Underlying Hearing and Emotions
Our work investigates neural mechanisms underlying the process by which emotional centers in the brain assign meaning to social vocalizations. Past experiments in our lab have found neurons in the amygdala that respond selectively to social vocalizations. We have examined how contextual cues associated with a social vocalization alter the interpretation of that vocalization by the individual and by neurons in the amygdala. We have shown that the behavioral and amygdalar response to a vocalization is differentially altered by exposure to olfactory cues associated with either mating or predators, and by internal levels of brain chemicals. We now propose to examine the mechanisms of selectivity for vocalizations as well as the source of contextual cues in the amygdala. Using electrical recording of nerve cell activity in the amygdala in response to mouse vocalizations, we will describe how different neurons of the amygdala respond to social vocalizations. Using gene insertion, optical imaging, and histological techniques, we will relate the response to vocalizations of amygdala cells to their connections to other brain regions. Using acoustic methods, we record and analyze mouse vocalizations to study how they change with behaviors.
Bradley Winters, Ph.D.
Literature review of cellular diversity in the lateral superior olive
The superior olivary complex (SOC) in the brainstem of mammals integrates information from the two ears enabling sound localization. This ability underlies selective auditory attention and is disrupted by hearing loss and in children with central auditory processing disorder (CAPD). Principal neurons of the lateral superior olive (LSO PNs) are critical for these functions. The classical view of the LSO is a homogeneous block of cells that extracts ongoing interaural level differences (ILDs), however, LSO is increasingly implicated in encoding interaural time differences (ITDs) for broadband transients and amplitude modulations. Cellular properties are fundamental to how neurons extract and encode information. ILD/ITD processing places disparate demands on neuronal properties and there is cellular diversity in the LSO that is not well-understood. It is also critical to understand how different types of information may be organized in higher processing centers of the inferior colliculus (IC).
We found that LSO PNs consist of inhibitory and excitatory cell types with different projection patterns, intrinsic membrane properties, and morphology. The student project will be to work with the PI in accessing and consolidating scientific literature on cellular diversity in the lateral superior olive.
Jesse Young, Ph.D.
Skeletal Muscle Development in the Sus Feeding & Locomotor Systems
This study utilizes a well-established precocial animal model it is possible to investigate aspects of newborn physiology, specifically changes in the musculoskeletal system from birth to adulthood. Currently, changes occurring at the tissue level of locomotor and feeding system skeletal muscle during ontogeny are not fully understood. This includes aspects of developmental plasticity and the extent to which genetic and environmental factors determine muscle fiber type. To increase our understanding of the changes which occur in different systems of skeletal muscle this study established the muscle fiber-type proportions of both the feeding and locomotor systems at three points of development (birth, pre-weaning, post-weaning) in a precocial species (pigs). This will be done through standard histological staining of muscle tissues (NADH-TR enzyme staining), and immunohistochemistry to isolate and count Type-I, Type-IIa, and Type-IIb muscle fibers. We hypothesize that the two systems will show similarities in fiber-type proportions at birth, but that the feeding system will show a unique and distinct maturation pattern, influenced by the changes which occur at weaning as the animals move from suckling to mastication. We expect that our results will add a critical understanding to the maturation of skeletal muscle, showing that as new ‘programs’ (mastication) are onboarded through development, muscle must subsequently respond to new functional requirements by adapting its fiber-type proportion to new demands.
CONTACT
Nona Hose
Phone: 330.325.6499
Email: nhose@380cebbe0d.nxcli.io
These projects are funded by the Office of Research and Sponsored Programs (ORSP).