UAF | UAMS
Mentors at the University of Arkansas for Medical Sciences
Faculty please note that this list of mentors is not exclusive. There are many more potential mentors on the UAMS campus. You can search at the UAMS web site and contact potential mentors yourself or seek assistance from Jerry Ware or Tom Kelly.
Undergraduate students applying to the INBRE Mentored Summer Research Program, please use the list of mentors below for your application.
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Mechanisms of Chemotherapy-Induced Cognitive Impairment (1UAMS)
Antiño R. Allen, Ph.D.
Division of Radiation Health, University of Arkansas for Medical Sciences
Chemotherapy is commonly used in the management of cancer, but its effectiveness is limited by the potential for injury to normal tissues. Chemotherapy induced cognitive impairment, also Referred to as“chemobrain”or“chemofog,”is experienced by 15 – 80% of cancer patients and survivors. The Allen laboratory is interested in understanding the mechanisms that are responsible for behavioral toxicities after cancer therapy. We currently have two active projects; the first is studying how chemotherapy after breast cancer affects cognition in adult female mice. The second project is investigating the neurocognitive late effects after acute lymphoblastic leukemia chemotherapy in a juvenile mouse model. Trainees in my lab learn and use a variety of techniques including: behavioral studies, molecular biology (PCR), biochemistry (protein expression, Western blots), immunohistochemistry, histology, light/fluorescent microscopy, cell culture and electrophysiology (brain slice recording) in order to answer questions at multiple levels of the investigation.
Bioinformatics students – No
Natural Language Processing (NLP) of Clinical Data (38UAMS)
Ahmad Baghal, MD
COM, Department of Biomedical Informatics, UAMS
Secondary use of clinical data for clinical and translational research is instrumental in growing our knowledge of clinical medicine. Unfortunately, not all clinical data are represented as discrete elements. Clinical practices generate enormous amounts of documents that store rich and valuable information that can enhance our knowledge discovery. The goal of the engagement is to perform an evaluation of open source NLP tools that can be suited to UAMS clinical environment, particularly within the Arkansas Clinical Data Repository (AR-CDR) domain. There is also a potential to participate in research work that focuses on developing new NLP pipeline using novel methodologies.
Prerequisite courses: Programming (Python/ knowledge of Databases)
Informatics students: Yes
Alzheimer Disease: Connections to Diabetes and Obesity (3UAMS)
Steven W. Barger, Ph.D.
Departments of Geriatrics, Neurobiology & Developmental Sciences, and Internal Medicine, University of Arkansas for Medical Sciences
The Barger laboratory studies basic elements of cellular neurobiology, particularly as they relate to the development of Alzheimer’s disease. Using cell cultures and transgenic mice, Dr. Barger and coworkers examine the ways in which the Alzheimer amyloid protein perturbs blood glucose levels and other elements of metabolism outside the brain. It is hypothesized that these “peripheral” perturbations, in turn, impair brain function in Alzheimer’s disease. An aspect of the project involves testing new drugs that might alleviate these abnormalities.
Pre-requisite courses: No
Bioinformatics students: Yes
DNase Inhibitors: Universal Anti-Disease Drugs of the Future (4UAMS)
Alexei G. Basnakian, MD, Ph.D., D.Sc.
COM, Department of Pharmacology and Toxicology, UAMS
All human diseases are associated with a tissue injury by a direct physical impact, infection, inflammation, hypoxia or poisoning. All of those induce cell death, which is a multi-step process. However, independently of the cause and mechanism of cell death, all they end up with DNA fragmentation by cellular endonucleases, including: deoxyribonuclease I, deoxyribonuclease II, caspase-activated DNase, endonuclease G, DNase gamma and a few other enzymes. Sometimes these enzymes are called “apoptotic endonucleases,” however they participate in necrosis, mitotic catastrophe, anoikis, and dysregulated autophagy as well. Our studies showed that genetic inactivation or inhibition of these enzymes universally protect cells from death in different models of cell or organ injuries in vitro and in vivo. We have recently discovered several specific chemical inhibitors of endonucleases and now test if they can be applied as drugs to protect healthy tissues against various types of tissue injury (diseases). Our first results in this direction are very encouraging.
Pre-requisite courses: None
Bioinformatics students: Yes
Understanding Lung Cancer Metabolism (5UAMS)
Gunnar Boysen, Ph.D.
Department of Occupational Health and Safety, UAMS
The Boysen lab interested in understanding the interplay between chemical exposure and nutritional or lifestyle habits, such as diet selection and physical activity. To achieve this we utilize DNA and protein adducts to study carcinogen metabolism, how it is modified by nutritional components and the underlying mechanisms regulating corresponding enzyme activities. In addition studies investigate exposures related changes in common metabolic pathways, using targeted and un- targeted mass spectrometry based metabolomic approaches. The long term goal is to improve our understanding of lung carcinogens and to improve lung cancer therapy.
Pre-requisite courses: None
Bioinformatics students: Yes
Using Molecular Genetics to Study Virulence in Pathogenic Borrelia (6UAMS)
Jon Blevins, Ph.D.
Department of Microbiology & Immunology, UAMS
Pathogens of the genus Borrelia are spirochetal bacteria transmitted to humans via the bite of an infected arthropod. There are two diseases, Lyme disease and relapsing fever, which are commonly associated with Borrelia infection in humans. Despite intensive research efforts studying the Borreliathat cause Lyme disease and relapsing fever, there is still significant progress to be made towards understanding pathogenic mechanisms that these bacteria utilize to cause disease, colonize tick vectors, and transmit during tick feeding. Specifically, we are working to determine how Borrelia controls the expression of its genes as it moves between tick and mammal and define contributions of individualBorrelia genes to bacterial virulence and tick colonization. One of the most direct approaches to demonstrate a causal relationship between a bacterial gene, its cognate gene product, and arequirement during the bacterial lifecycle is to create Borrelia strains in which specific genes of interest have been inactivated. The abilities of these mutant strains to colonize animals and ticks can then be assessed experimentally to determine whether a given mutant is no longer competent for infection. Once bacterial factors required for Borrelia infection or tick transmission have been identified, we can begin to study their physiological contributions to these bacterial processes. In addition, since these factors are known to be essential during the bacterial lifecycle, they also represent viable targets against which therapies could be developed to prevent or treat disease.
Pre-requisite courses: Microbiology (Preferred)
Dynamics of Regulation and Function of Diverse Subsets of Anterior Pituitary Cells (8UAMS)
Gwen V. Childs, Ph.D.
COM, Department of Neurobiology and Developmental Sciences, UAMS
Classical studies of the anterior pituitary have shown 6 major cell types with unique neuropeptide releasing hormones as regulators from the brain. However, sensitive molecular assays show that pituitary cells are much more diverse than previously believed. Currently the funded projects in Childs laboratory focus on two examples of this diversity. The first study focuses on the significance and regulation of leptin by specific pituitary cells. Leptin is an appetite regulatory peptide normally produced by adipose cells. However, it might also be a cytokine in the pituitary, working locally to regulate pituitary cells. One project even looks at the possibility that it might be an endocrine factor, produced by gonadotropes to help regulate the reproductive system. The second study focuses on how pituitary cells integrate responses so that a cocktail of hormones is released to meet the needs of a particular physiologic state. Co-expression of multiple neuropeptide receptors is one of the ways the cells can meet these needs and this is regulated by gonadal steroids. The studies use molecular cytochemistry and cytophysiology with a focus on the analysis of individual cells.
Pre-requisite courses: Cell Biology
Bioinformatics students: No
Molecular Mechanisms of DNA Damage Tolerance in Cancer (9UAMS)
Robert L. Eoff, Ph.D.
COM, Department of Biochemistry and Molecular Biology, UAMS
The Eoff laboratory explores mechanisms that allow tolerance of DNA damage that would otherwise block normal cellular processes. We use a variety of approaches to investigate the structure and function of translesion DNA polymerases, enzymes that facilitate bypass of DNA damage and other endogenous barriers to replication (e.g. G-quadruplex DNA). Studying the relationship between aberrant activation of DNA damage tolerance and adverse outcomes for cancer patients (e.g. progression to malignancy, resistance to therapy, and maintenance of the cancer stem cell niche) is a central theme in the laboratory. Our work is supported by the National Institutes of Health and the National Science Foundation. We have an ongoing collaboration with the laboratories of Dr. Analiz Rodriguez (UAMS, Neurosurgery) and Prof. Peter Crooks (UAMS, Pharmaceutical Sciences) to develop small-molecule inhibitors of translesion DNA polymerases in an effort to potentiate existing drugs used to treat brain tumors. We also collaborate with Dr. Julie Gunderson (Hendrix College) to investigate the proteins and enzymes that participate in G4 DNA replication and maintenance. Through our research, we hope to contribute new insights into mechanisms that are central to mutagenesis, cancer biology, antibiotic resistance, and evolution.
Pre-requisite courses: None
Bioinformatics students: No
Virus-Host Interactions in Gammaherpesvirus Infections (11UAMS)
J. Craig Forrest, Ph.D.
COM, Department of Microbiology & Immunology, UAMS
Virology, cancer biology, immunology! Gammaherpesviruses, such as Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus, are cancer-causing viruses that infect the majority of humans. We are working to define functions of viral proteins in infection and disease, identify host factors that block viral infection and prevent virus-driven cancers, and understand immune responses to chronic viral infections. We use a multi-disciplinary approach that includes basic cell biology, molecular genetics, global proteomics, and mouse models of infection to accomplish our major goal of defining the complex relationship between gammaherpesviruses and their hosts. PLUS, we get to do cool science and figure out how stuff works!
Pre-requisite courses: Biology and Chemistry
Bioinformatics students: No
Radiation-activated Nanoparticles for Cell Killing and Liposomal Drug Delivery (13UAMS)
Robert J. Griffin, Ph.D.
COM, Department of Radiation Oncology, UAMS
Besides surgery, treatment with radiotherapy and chemotherapy remain the best options for a positive outcome. Simultaneous application of these therapies, which enhances the clinical response to treatment, is limited by harmful systemic sequelae inherent to non-local drug delivery. As such, a central unmet challenge for drug delivery systems is the ability to release drug at the desired location in a controlled manner and not flood normal tissues with high doses of drug. Ideally, the drug should be transported to the desired site in a specialized vehicle to protect the drug from acting until an externally controlled stimulus triggers drug release at the target site. Stealth® liposomes have great potential as a vehicle that can carry drug cargo in a protected state and evade detection by the body’s self defense mechanisms. However, controllable drug release from liposome carriers remains problematic. A current focus and goal in the Griffin laboratory is to use X-ray radiation as a trigger for controllable drug release preferentially at the irradiated site using innovative chemistries loaded into our liposome or by using nanoparticles coated with xray sensitive substances. One project is working with patented and patent-pending methodologies for in vitro optimization of drug release upon X-ray exposure using irradiation doses that resemble a typical conventional (low dose) or hypofrationated (high dose) radiotherapy session. Another related project is focused on loading/coating X-ray responsive nanoparticles to induce production of tumor cell killing free radical species after specific radiation dosing of 3-D tissue volumes by radiation therapy. Triggering of drug or radical release at the target site by precisely applied X-ray radiation is possible due to the unique ability of designer nanoscintillators to emit various types of light upon X-ray absorption. The emitted light then acts to release ions from a caged compound, which can lead to drug release from liposomes or production of toxic radicals. We aim to validate and optimize these innovative approaches using in vitro models and cell culture techniques. Extended studies include in vivo solid tumor and normal tissue investigations (using mouse or rat tumor models) of the optimized drug release and nanoparticle activation mechanisms that utilize therapeutic X-ray doses and will establish the biodistribution patterns of nanoparticles and chemotherapy after i.v. administration before and after tumor irradiation. By using this approach, radiotherapy and chemotherapy can be simultaneously applied at optimal dosing to achieve a more effective cancer treatment through supra-additive effects stemming from the combined therapy, and minimized side effects due to lower exposure of normal tissues to free drug.
Pre-requisite courses: Cell Biology and/or Biochemistry, Physiology recommended
Bioinformatics students: Yes
Food Safety and New Antimicrobial Discovery (16UAMS)
En Huang, Ph.D.
Department of Occupational Health and Safety, UAMS
The main theme of my research is to discover and develop novel antimicrobial peptides (e.g., bacteriocins and lipopeptides). These antimicrobial agents have the potential to be used as natural food preservatives, animal feed additives or novel antibiotics against drug-resistant bacterial pathogens.
Website: Huang Lab Website
Pre-requisite courses: Microbiology lab
Bioinformatics students: Yes
Preclinical modeling of cancer immunotherapy (55UAMS)
Brian S. Koss, Ph.D.
COM, Department of Biochemistry and Molecular Biology
The Koss lab is dedicated to unraveling the intricacies of T cell biology within the context of solid tumors. Our primary focus is on understanding the factors driving T cell dysfunction within the solid tumor environment. Our ongoing projects center around T cell metabolism, DNA repair, and protein turnover, aiming to shed light on critical aspects of T cell function. To bridge the gap between research and application, we are actively engaged in developing new immune monitoring methodologies and engineering cellular T-cell therapies. A cornerstone of our approach involves leveraging proteomics to explore the depths of T cell biology, and we offer support and training in this specialized field. Our work spans both human and mouse primary cell culture, as well as pre-clinical mouse models of cancer immunotherapy, enabling comprehensive training opportunities. Lab website: https://thekosslab.com/
Pre-requisite courses: No, but Biology, Immunology, and/or Chemistry is desired.
Bioinformatics students: Yes
Neurocognitive Dynamics (18UAMS)
Linda J. Larson-Prior, Ph.D.
COM, Department of Neurobiology & Developmental Sciences, UAMS
My laboratory is interested in better understanding the dynamic neural network re-configurations that occur as the brain changes its state under normal conditions such as sleep, and in abnormal conditions such as induced shifts in conscious awareness (anesthesia), pathological shifts in cognitive awareness (fluctuating consciousness, sleep parasomnias and neurodegenerative disease states), or changes in the response to external environments (depression, anxiety). The laboratory uses multimodal neuroimaging methods, including have electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to help us better understand these changes in network connectivity and function as the brain shifts state over the course of 24 hours. As part of the Human Connectome Project, my laboratory worked with a large international team to define the connection patterns in normal adult human subjects using magnetoencephalography (MEG) and fMRI methodologies. Connectomics and biomedical informatics approaches to analysis of large, multi-modal datasets is an area my laboratory is actively pursuing to better understand the role of behavioral and neural state on function across the lifespan. The laboratory is currently working to understand the neurobiological mechanisms that underlie cognitive homologues of freezing of gait in Parkinson’s Disease, the impact of poor sleep on the ability of patients seeking treatment for opioid used disorder to adhere to treatment protocols and achieve treatment success, and the effects of epilepsy and it treatment on memory function. In addition to my research focus, I have a strong commitment to mentoring of students at all levels, from undergraduates (INBRE, REU programs) to junior faculty members, and on doctoral thesis committees and departmental mentoring committees.
Pre-requisite: None
Bioinformatics students: Yes
Virus-Host Interactions during Poxvirus Infections and Immunotherapeutics Using Poxviruses (19UAMS)
Jia Liu, Ph.D.
COM, Dept. f Microbiology and Immunology, UAMS
Join us to learn about virology, Immunology, and cell biology! We use large DNA viruses, called poxviruses, to investigate how host immune response work. These powerful viruses can also effectively inhibit host responses and we study how they do that, so that we can develop ways to prevent disastrous infectious diseases caused by them. Poxviruses are also fantastic tools to study evolution on virus-host interactions. You can examine millions of years long evolution process under your eyes in short a few weeks! More importantly, by genetic manipulation we can engineer viruses to treat cancer! We learn the tricks from viruses and use them to kill cancer cells! We adopted multidisciplinary approaches for our work, which include proteomics, cell biology, molecular virology, and animal models (mouse and rabbit) to test our hypotheses and to confirm treatment effectiveness. There are so much more to learn about the host and the cool viruses. Join us, you can make differences in science and therapy!
Pre-requisite course: biology, chemistry, or genetics
Bioinformatics students: Yes
Molecular Mechanisms of Intracellular Membrane Trafficking (20UAMS)
Vladimir Lupashin, Ph.D.
COM, Departments of Physiology and Cell Biology, UAMS
The Lupashin laboratory is employing state of the art genetic, cellular and microscopy approached (CRISPR/Cas9-directed gene editing, super resolution microscopy, in vitro reconstruction) to uncover the molecular mechanisms responsible for generation and maintenance of intracellular membrane-bounded compartments in eukaryotic cell. Specifically, we study the machinery that directs docking and fusion of intracellular transport vesicles. The major player of vesicle tethering machinery at the Golgi apparatus is Conserved Oligomeric Golgi (COG) complex. Mutations in COG subunits cause Type II Congenital disorders of glycosylation in humans. COG complex dysfunction in cultured cells results in glycosylation and endo-lysosomal disorders. We are investigating the molecular mechanisms of COG complex action in different human cell lines. We also investigating mechanisms that pathogenic microorganisms and toxin use to hijack trafficking compartments in human cells.
Pre-requisite courses: None
Bioinformatics students: Yes
Bone Biology and Disease Mechanisms in Osteogenesis Imperfecta (Brittle Bone Disease) (34UAMS)
Roy Morello, Ph.D.
COM, Department of Physiology and Cell Biology, UAMS
In my laboratory we study the function of novel genes, in particular those involved in connective tissue formation, development, homeostasis and disease, with an emphasis on the skeleton. We utilize the power of mouse gene targeting and conditional gene-inactivation techniques to generate ubiquitous or tissue-specific mutations in the mouse. With the use of cell biology, biochemistry, cell microscopy, proteomic and genetic approaches we characterize the phenotype of genetically-modified mice to understand the underlying gene function. The objective is to learn from the animal model and make correlations with relevant aspects of human disease and hence gain mechanistic insights of biological function. Of particular interest is the study of the disease osteogenesis imperfecta (also known as brittle bone disease) and the underlying pathogenetic mechanisms that lead to low bone mass but also respiratory disease, and to the study of the role of osteocytes in the disease process.
Integrating data-mining, modeling and experimental approaches to develop safer targeted cancer therapeutics (22UAMS)
Grover Paul Miller, Ph.D.
COM, Department of Biochemistry and Molecular Biology, UAMS
Recent advances in targeted cancer therapeutics boast superior health outcomes relative to traditional chemotherapy drugs; however, hepatotoxicity poses a major clinical concern for patients undergoing treatment with these revolutionary drugs. Drug metabolism plays a central role in toxicological mechanisms and thus, my research focuses on assessing clearance and bioactivation of drugs and subsequent biological, pharmacological and toxicological impacts on human health. In practice, my group integrates and leverages powerful analytical, biochemical, and computational tools to identify and quantitate small molecules including drugs, pollutants, and food additives during metabolism and correlate findings to biological activity and in vivo outcomes such as liver toxicity. Specific projects involve targeting drug classes prone to bioactivation for establishing a mechanism(s) to interpret and explain observed toxicity. We will assess oxidative steady-state metabolism including bioactivation of drugs using human liver microsomes as a model for the liver. This work will rely on HPLC coupled to UV/Vis, fluorescence and MS detection for quantitating metabolites and translating the data into reaction kinetics to assess metabolic fluxes down bioactivation and detoxification pathways. In subsequent studies, we will employ inhibitor phenotyping to identify potential cytochrome P450 isozymes responsible for metabolism and then carry out steady-state metabolic studies with recombinant forms of those enzymes. As an alternate, faster analysis of drug metabolism and bioactivation, we will employ deep neural network models to predict the sites and likelihood for metabolism, and then compare those findings to results from experimental studies. Knowledge gained from these studies will aid in the design and use of safer targeted cancer therapeutics by minimizing associated toxicities that limit their use in the clinic.
Pre-requisite courses: None
Bioinformatics students: Yes
Mechanisms of Action of DNA and RNA Helicases (24UAMS)
Kevin D. Raney, Ph.D.
COM, Department of Biochemistry and Molecular Biology, UAMS
The Raney laboratory is studying the mechanisms of action of DNA and RNA helicases in work that is funded by the National Institutes of Health. These enzymes manipulate DNA and RNA and enable replication and repair of genomes. Another project is focused on non-canonical forms of DNA, such as quadruplex DNA. Biochemical and molecular biological techniques are used for in vitro and cellular experiments.
Prerequisites: General Chemistry, Organic Chemistry
Bioinformatics student: No
Genetic and Metabolomic Predictors of Longevity and Age-Associated Diseases (25UAMS)
Robert J. S. Reis, D.Phil.
Depts. of Geriatrics and Biochemistry & Molecular Biology at UAMS and the McClellan Veterans Medical Center (CAVHS), UAMS
We have an NIH Program Project grant to quantitate metabolite levels and measures of metabolic activity and damage, as well as the status of antioxidant defenses. We will use these to formulate robust predictors of future longevity in young adults, for a variety of model systems in which life span can be extended markedly by genetic or dietary means. We will then seek common “fingerprints” indicative of future survival that may extrapolate to humans. A database will be developed and a variety of means of data mining will be employed to interrogate it. In the near future, we also plan to develop databases comprising a panel of measures (both those of known clinical prognostic value, and some of the novel markers developed in our model systems), monitored in healthy human subjects. We can thus look for new markers that correlate well with established biomarkers, and evaluate the application of these metabolic profiles to predicting susceptibility to common diseases and conditions associated with reduced fitness (e.g., obesity, diabetes/impaired glucose tolerance, cancer, high blood pressure, and cardiovascular impairment).
Pre-requisite courses: None. Prior courses and/or experience with databases and/or data mining are desirable but not essential.
Bioinformatics students: Yes
Molecular Pathogenesis of Staphylococcus Aureus Musculoskeletal Infection (27UAMS)
Mark S. Smeltzer, Ph.D.
COM, Department of Microbiology and Immunology, UAMS
Research in the Smeltzer laboratory focuses on Staphylococcus aureus as a musculoskeletal pathogen. We are particularly interested in the surface-exposed adhesions and other virulence factors that allow S. aureus to avoid host defenses and efficiently colonize host tissues and indwelling medical devices, the regulatory circuits that control expression of these virulence factors, and the mechanism(s) by which these factors contribute to the pathology of orthopaedic infections. We are also exploring novel therapeutic methods including the use of nanotechnology as a means of eradicating an established biofilm.
Pre-requisite courses: Microbiology lab
Bioinformatics students: Yes
Cellular Mechanisms of Antibody-mediated Immunity against Plasmodium Infection (28UAMS)
Jason Stumhofer, Ph.D.
COM, Department of Microbiology and Immunology, UAMS
The Stumhofer laboratory studies basic elements of the immune response against the malaria parasite Plasmodium. Using rodent models of infection we are conducting studies to determine the cellular requirements for the development of antibody-mediated protective immunity to Plasmodium. Also, we are interested in determining how and when memory B cells are formed after Plasmodium infection, and their contribution to protection upon secondary infection. Collectively, our studies will provide valuable information regarding the cellular events that contribute to protective immunity against malaria that will be vital for effective vaccine development.
Pre-requisite courses: Microbiology
Bioinformatics students: No
Mechanisms of Intracellular Bacterial Pathogenesis (29UAMS)
Daniel E. Voth, Ph.D.
COM, Department of Microbiology & Immunology, UAMS
The Voth laboratory is focused on understanding mechanisms used by bacterial pathogens to parasitize host cells and cause pulmonary disease. Specifically, we are studying Coxiella burnetii, which causes human Q fever, an acute debilitating flu-like illness that also presents as life threatening chronic endocarditis, and Staphylococcus aureus, which infects numerous tissues in the human body. We are currently studying host signaling pathways manipulated by C. burnetii to generate an intracellular replication compartment with lysosomal features. Additionally, we are characterizing secreted C. burnetii proteins that influence host processes during infection and are predicted to be major virulence factors. We are also studying the role of cytolytic toxins in S. aureus infection of human lungs. Collectively, our studies will provide new insight into the complex interplay between pulmonary bacterial pathogens and humans.
Prerequisites: Cell Biology or Biochemistry
Bioinformatics students: No
The Platelet Paradigm in Thrombosis, Inflammation and Cancer (30UAMS)
Jerry Ware, Ph.D.
Department of Physiology and Cell Biology, UAMS
The Ware laboratory studies fundamental aspects of platelet biology to elucidate their role of in hemostasis, thrombosis, and inflammation. Since platelets are anucleate fragments of cytoplasm, in vivo models are used based on the hypothesis that the unique cellular characteristics of megakaryocytes and platelets require the correct in vivo environment for meaningful assessment of biological properties. Currently, we are characterizing the platelet’s role in modulating the inflammatory processes associated with sepsis. The clinical management of sepsis remains a challenging and difficult problem and the goal of our work is better understand the complex pathophysiology associated with sepsis.
Pre-requisite courses: None
Bioinformatics students: Yes
Study of Multiple Myeloma Progression and Bone Metabolism Using Cancer Cells and Animal Models (31UAMS)
Donghoon Yoon, Ph.D.
Myeloma Institute, University of Arkansas for Medical Sciences
Multiple myeloma (MM) is a B cell cancer characterized by the proliferation of malignant plasma cells in the bone marrow, the presence of monoclonal serum immunoglobulin, and bone lesions. Previous studies demonstrate that bone de-structuring is highly related to Myeloma progression. Our laboratory is studying the effects of various bone-forming factors on bone metabolism and MM progression using cell lines and animal models. Trainees in my laboratory will learn cell culture, cell proliferation assays with drug treatment, monitoring drug-treated mice, and their effects on MM progression using in vivo mouse imaging techniques.
Prerequisite course: Cell biology
Bioinformatics students: Yes
Role of Infant Diet in Gastrointestinal Tract Development and Immune Function (32UAMS)
V. Laxmi Yeruva, Ph.D.
Department of Pediatrics, UAMS, ACNC/ACRI
Breastfeeding is known to impart a variety of positive effects on offspring health, including immune system development, and to lower risk for a variety of diseases. Yet, the exact mechanisms underlying these outcomes are not fully known. Research in the Nutritional Immunology group is centered around understanding the early-life events that program gut development, gut microbe ecology and immune function. To address the questions we use a piglet model and a variety of techniques including immunology, immunohistomorphometry, molecular biology (16sRNA sequencing for microbiome, RNA seq analyses), and metabolomics (LC/MS). The big data are analyzed in collaboration with Bio-informatics team at ACNC (Lead by Dr. Brian Piccolo). Ongoing research seeks to determine the effects of early diet on GI development and function and to what extent these effects are secondary to differences in the gut microbiota, and also immune function. The student interested will be assisting in addressing the short-term goals of our project.
Pathogen Research – My second area of research at Arkansas Children’s Research Institute (ACRI) focuses on health-oriented basic and translational studies of immunity. The goals of my study are to understand the factors that induce pathologic immune responses following Chlamydia genital infections, and to develop markers of disease severity following sexually-transmitted infections, and to translate this research into clinically-relevant prevention and intervention strategies for sexually-transmitted infections.
Prerequisite courses: No
Bioinformatics students: Yes
Translational Brain Tumor Research (33UAMS)
Analiz Rodriguez, MD, Ph.D.
COM, Department of Neurosurgery, UAMS
My laboratory focuses on the development of therapeutics for brain tumor treatment. We have integrated multiple omics platforms (i.e. genomics, transcriptomic, and proteomics) to identify therapeutic targets. I established a precision medicine platform in our department in which all patients receive prospective sequencing of their brain tumor. I am also developing patient derived organoid modeling to test therapeutics.
Prerequisite courses: No
Bioinformatics students: No
Maternal Obesity Programming of Offspring Vascular Function (34UAMS)
Keshari Thakali, Ph.D.
Arkansas Children’s Nutrition Center and Department of Pediatrics, UAMS
Currently, many women entering pregnancy are either overweight or obese and it has been observed that maternal obesity during gestation is associated with increased risk of offspring cardiovascular disease. The Thakali lab performs research on understanding how maternal obesity during pregnancy programs offspring cardiovascular dysfunction. To accomplish this goal, female mice are fed either control or high fat diet (HFD) prior to mating with lean male mice, and maintained on their respective diets throughout pregnancy and lactation. At weaning, male and female offspring are fed control or HFD, and offspring cardiovascular parameters including arterial blood pressure, vascular inflammation, and smooth muscle, endothelial cell, and perivascular adipose tissue function will be assessed. Other techniques we commonly use in the lab include next-gen sequencing (RNAseq), molecular biology (qPCR), biochemistry techniques (protein expression), and immunohistochemistry.
Pre-requisite courses: None
Bioinformatics students: Yes
Exploring the Role of DNA Secondary Structures in Lymphoma (35UAMS)
Samantha Kendrick, Ph.D.
COM Biochemistry & Molecular Biology Department, UAMS
Our overall research goal is to identify the molecular mechanisms behind the genomic instability at critical oncogenes in lymphoma and the role DNA secondary structures may play in facilitating these genomic alterations. We are also interested in understanding the impact of HIV infection on the molecular oncogenesis of lymphoma and developing new therapies for aggressive lymphoma through targeting oncogene expression. To address these important questions, we integrate basic and translational science using in silico, ex vivo, cell-based and tissue-based genomic and proteomic approaches.
Pre-requisite courses: None
Bioinformatics students: Yes
Deciphering the DNA Damage Response Pathway (36UAMS)
Justin W Leung, Ph.D.
COM Department of Radiation Oncology, Winthrop P. Rockefeller Cancer Institute, UAMS
Our Laboratory studies genome stability in the context of chromatin. Our research focuses on understanding the molecular mechanistic regulation that encompasses the DNA damage response (DDR) pathway. We are interested in dissecting the roles of chromatin modifications in eukaryotic cells. We also study the detailed mechanism of DDR proteins in orchestrating the repair process as well as their implication in genetic diseases. We are currently conducting genetic and proteomic studies to identify novel components of the DDR and define new genetic, functions and physical interactions between DDR pathways. These studies will provide greater insights into the complex mechanisms by which the DDR maintains genomic stability.
Pre-requisite courses: None
Bioinformatics students: Yes
Real-Time Pathogen Surveillance for Infection Prevention and Antibiotic Stewardship (37UAMS)
Se-Ran Jun, Ph.D.
COM, Department of Biomedical Informatics, UAMS
Antibiotic resistance (AR) ranks today as one of the most significant global health concerns, presenting challenges that affect not only individual clinics and hospitals, but also threaten worldwide public health. Hospital-acquired infections by antibiotic resistant pathogens are a significant cause of morbidity and mortality, particularly in immunocompromised patients. With a major driver of AR being antibiotic misuse, this practice both increases the rate of AR and fuels the course of transmission of these infectious agents within and between hospitals.
Dr. Jun’s lab has a particular focus on genomic pathogen surveillance for infection prevention and antibiotic stewardship with goals of development of a system with 1) fast enough turnaround time and 2) discriminatory power to impact antibiotic stewardship decision and to assist in breaking transmission routes to improve interventions made by infection prevention teams.
Prerequisite courses: None
Bioinformatics students: Yes
Innate Immune Defense Against Intracellular Pathogens (39UAMS)
Youssef Aachoui, Ph.D.
COM, Dept. of Microbiology & Immunology, UAMS
We study how the innate immunity detect intracellular pathogens and subsequently orchestrate their elimination. We specifically focus on cytosolic pathogen pattern recognition detectors, inflammasomes, which activate caspase-1. Caspase 1 subsequently activates the processing of the pro-inflammatory cytokines pro-IL-1β and pro-IL-18 and/or promotes a form of programmed cell death termed pyroptosis. Pyroptosis restricts intracellular bacterial growth by lysing infected cells, thereby eliminating the intracellular replication niche, and exposing the bacteria to attack by neutrophils. For instance, we showed that the inflammatory caspase-11 discriminates between cytosolic and vacuolar bacteria, and this detection is necessary for protection against cytosolic pathogens such as Burkhloderiaspecies, and the ΔsifA mutant of Salmonella typhimuriumthat aberrantly exits the vacuole. We went on to show that caspase-11 is activated in response to cytosolic LPS. Current studies examine the activation of caspase-1 and caspase-11 inflammasones, and investigates their role in infection and inflammatory disorders.
Prerequisite courses: No
Bioinformatics students: No
Pharmacological Modulation of Poly(ADP-ribose) Metabolism (40UAMS)
Darin E. Jones, Ph.D.
Department of Pharmaceutical Sciences, UAMS
Molecularly-targeted cancer therapies have revolutionized the treatment of this heterogeneous and increasingly prevalent disease. Genetic instability is a hallmark of many cancers that generates mutations to support uncontrolled tumor growth and resistance to chemotherapies. The underlying DNA repair defects in these tumors can be exploited in tumor-selective therapies that block critical remaining DNA repair functions to trigger catastrophic damage and cell death. This idea is borne out by the clinical successes of inhibitors of poly(ADP-ribose) polymerase 1 (PARP1) to treat breast and ovarian cancers with mutations in BRCA1 or BRCA2. However, these BRCA-deficient tumors account for a minority of cancers so it is important to identify other physiological defects of tumors that are synthetically lethal in combination with molecularly targeted therapies. Additionally, the current PARP inhibitors suffer from dose-limiting toxicities, which may result from off-target effects on other members of the large PARP superfamily. As an alternative to PARP inhibitors, we used high-throughput screening to identify selective inhibitors of the human poly(ADP-ribose) glycohydrolase PARG. PARG is a monogenic enzyme that removes the poly(ADP-ribose) posttranslational modification of proteins modified by PARP1. A genetic knockdown of PARG sensitizes cancer cells to DNA damaging agents and radiation and phenocopies the tumor-specific killing effects of PARP1 enzymatic inhibitors in BRCA- deficient cancer cells. We utilize structure-guided chemical synthesis and in vitro testing, to improve the potency and selectivity of small molecule PARG inhibitors. Selected compounds are advanced to preclinical trials of tumor killing activity in cultured cells and xenograft models of breast cancer. We design and synthesize focused libraries of analogs that exploit unique features of the PARG active site and screen small molecule fragment library to identify new chemotypes and interactions that are incorporated into our inhibitor design strategy. Selective inhibitors of PARG will be useful probes of cellular responses to cancer chemotherapeutics that damage DNA, and may be useful cancer therapies in their own right by exploiting the genomic instability phenotype of many tumors.
Pre-requisite courses: Organic chemistry
Bioinformatics students: Yes
Development of Precision Medicine for Oncology (41UAMS)
Brendan Frett, Ph.D.
COP, Department of Pharmaceutical Sciences, UAMS
Drug development is largely target-driven, where drugs are developed to modulate a pharmacologically, relevant target in a given disease state. This type of drug development has been heavily utilized for oncology to improve effectiveness and reduce toxicity to chemotherapy. The Frett laboratory is interested in further improving target-based drug discovery in oncology. We have numerous, active projects which aim to uncover next-generation strategies to target malignant disease. Trainees in my laboratory learn a variety of techniques including organic chemistry (drug synthesis), analytical chemistry, biochemistry (drug/target studies), and cell culture all in the context of drug discovery and development.
Prerequisite courses: No
Bioinformatics students: Yes
Molecular mechanisms of maintenance of genomic stability to aid in development of new cancer therapeutics (42UAMS)
Alicia Byrd, Ph.D.
COM, Department of Biochemistry and Molecular Biology, UAMS
The Byrd lab focuses on enzymes involved in the DNA damage response, in particular, a family of enzymes called helicases that remove secondary structures from DNA. These proteins have critical roles in DNA repair and loss of activity results in genomic instability and predisposition to many types of cancer. We are studying the specific role and molecular mechanism of a helicase in responding to replication stress and DNA damage in cultured human cells and in vitro. This involves microscopy of both cells and single-molecule DNA fibers, UV/Vis spectroscopy, flow cytometry, and quantitative PCR. The effects of absence of an enzyme are determined using CRISPR knockout cells. In vitro, the effect of mutations on the enzyme activity are assessed using electrophoresis and fluorescence spectroscopy. Increased understanding of these DNA repair processes that are critical for maintaining genomic integrity could ultimately lead to the design of better cancer therapies.
Pre-requisite courses: None
Bioinformatics students: No
Role of Rho GTPases in cell migration and invasion (43UAMS)
Katie R. Ryan, PhD
COM, department of Biochemistry & Molecular Biology, UAMS
Our laboratory focuses on the identification of molecular mechanisms and signaling pathways involved in Rho GTPase signaling. Rho family GTPases act as ‘molecular switches’ and are master regulators of many aspects of cellular behavior including regulation of the actin cytoskeleton, gene expression, cell cycle, cell migration, and apoptosis. Many cellular processes regulated by Rho GTPases, are commonly dysregulated in cancer. We are currently focusing on the role of Rho GTPases in cell migration and invasion in several in vitro cancer models including breast and lung cancer. We utilize common molecular and cellular biology techniques as well as proteomic approaches to identify novel therapeutic targets of metastasis.
Pre-requisite courses: None
Bioinformatics students: Yes
Control of Bone and Muscle Weakness by Hormones and Nutrition (44UAMS)
Teresita Bellido, Ph.D.
COM, Department of Physiology and Cell Biology, UAMS
Research projects in the Bellido lab center on understanding physiological and pathophysiological mechanisms that govern the function of bone and muscle in health and disease, and developing genetic and pharmacological approaches to promote musculoskeletal health. Particular emphasis is placed on the role of osteocytes, the most abundant cells of bone, in driving the bone remodeling process in response to mechanical and hormonal cues, as well as in the role of these cells in cancer in bone and in multiple myeloma bone disease.
Current projects in the lab are:
- Mechanism of action of glucocorticoids in the musculoskeletal system
- Parathyroid hormone (PTH), osteocytes, and diabetes-induced bone disease
- Role of Osteocytes in cancer in bone in multiple myeloma
- Nutrition, bone, and the microbiome
The laboratory receives funding from the National Institutes of health (NIH), the Veteran Administration (VA), and the biopharmaceutical industry.
Pre-requisite courses: None
Bioinformatics students: No
Effect of Cancer Cells in the Skeleton (45UAMS)
Jesús Delgado-Calle, Ph.D.
COM, Department of Physiology & Cell Biology, UAMS
The Delgado-Calle laboratory investigates the mechanisms by which myeloma cancer cells alter the biology of other cells in the tumor/bone marrow microenvironment, particularly osteocytes, with the final goal of identifying targetable factors for the treatment of multiple myeloma and its associated bone disease. We employ a combination of in vitro, ex vivo and in vivo mouse models to study tumor biology and characterize the effects of tumor cells on bone remodeling. Current projects in the laboratory investigate the effects of Wnt and Notch signaling communication between myeloma cells and bone cells on tumor growth, cancer cell dormancy, and bone destruction. Other projects in the laboratory investigate the crosstalk between bone and adipose tissues that regulates body fat and whole-body metabolism.
Pre-requisite courses: None
Bioinformatics students: No
Skeletal Aging: Role of Autophagy and Osteocytes in age-associated bone loss (46UAMS)
Melda Onal, Ph.D.
COM, Department of Physiology and Cell Biology, UAMS
Osteoporosis is a common bone disease in which bones become weak and brittle to a point that falls or even mild stressors such as coughing can cause fractures. Old age is the most significant risk factor for the development of osteoporosis. Several mechanisms have been proposed to contribute to age-related pathologies in various tissues. Autophagy is a proteostasis mechanism in which cellular components are recycled in lysosomes to adapt to changing nutrient conditions or clear damaged/malfunctioning/ excess cytoplasmic contents in order to maintain cellular homeostasis. A decline/dysfunction in different types of autophagy has been proposed to be a contributor of age-associated pathologies in several tissues, in particular in long-lived cell types. In our laboratory, we use a combination of in vivo and in vitro molecular and cell biology techniques to examine the contribution of different types of autophagy to age-related bone loss. In addition, as part of our quest to address mechanisms underlying age-related bone loss, we are utilizing CRISPR interference technology to develop murine loss of function models that are specific to osteocytes, the long-lived cells of bone.
Pre-requisite courses: None
Bioinformatics students: No
Investigating the epigenetic regulatory mechanisms and therapeutic interventions in Acute Myeloid Leukemia (47UAMS)
Samrat Roy Choudhury, Ph.D.
Arkansas Children’s Research Institute (ACRI), COM Department of Pediatrics, UAMS.
Our laboratory investigates the epigenetic mechanisms at the regulatory regions (enhancers and promoters) of critical oncogenes and tumor suppressors that drive malignant proliferation and tumor infiltration of the leukemic cells. Using multi-omics platform, the laboratory studies alterations in DNA-methylation, histone modifications and binding of the transcription factors to the aberrantly expressed genes. We use bioinformatic tools to integrate epigenomic and transcriptomic data to determine the epigenetically dysregulated pathways in the disease. The laboratory also uses a combination of in vitro and in vivo mouse models to screen small molecule-based chemotherapies to reverse the dysfunctional epigenetic states and overall malignant growth.
Pre-requisite courses: None
Bioinformatics students: Yes
Anti-cancer Activity of Derivatives of Natural Products (48UAMS)
Alicja Urbaniak, M.Sc., Ph.D.
COM, UAMS Department of Biochemistry and Molecular Biology
Research interests in the Urbaniak Lab lie at the interphase of chemistry and cancer biology. Our Lab intends to tackle the most pressing issues in cancer biology – how to target and therapeutically intervene to disrupt cancer stem cell functionality (self-renewal, drug resistance, tumor recurrence after therapy, and metastatic spread to distant organs). The lab is especially interested in breast cancer biology and discovery of novel small molecules with anti-breast cancer properties. We are particularly focused on the anti-cancer stem cell activity of polyether ionophore antibiotics and their derivatives. currently the lab is developing 3D tumor organoid models to better mimic tumor architecture and to facilitate rapid screening of small molecule drug candidates selectively active against cancer stem cells.
Pre-requisite courses: None
Bioinformatics students: No
The Role of the Mitochondrion in the Metabolic Stress Response to Burn Trauma (49UAMS)
Craig Porter, Ph.D.
COM, Department of Pediatrics
Trauma is the principle cause of unexpected death in people aged 1 to 46 years in the U.S. The annual cost of treating trauma patients exceeds the combined cost of treating cancer and heart disease patients. Burns are a leading cause of non-fatal trauma in the US. Severe burns result in a devastating metabolic stress response that causes long-term morbidity and reduced quality of life in burn survivors. Hypermetabolism (increased energy expenditure), cachexia, hepatomegaly, and immune dysfunction are all hallmarks of the metabolic stress response to burns. Recent evidence suggests a central role of the mitochondrion in this stress. The goal of this research program is to advance our understanding of the role of the mitochondrion in the metabolic stress response to burn trauma. By leveraging innovative animal models and studying patients, our long-term objective is to generate new knowledge that will aid in the development of strategies that reduce suffering and promote the recovery of burn survivors.
Pre-requisite courses: None
Bioinformatics students: No
The Role of Tumor Vasculature in Carcinogenesis and Treatment (50UAMS)
Ruud P.M. Dings, Ph.D, M.Sc.
COM, Department of Radiation Oncology
The primary goal of our lab is to enhance our understanding of vascular biology to discover and develop improved methods for cancer treatment. Our major research interest is the tumor microenvironment, with emphasis on the crosstalk between the immune system and the tumor vasculature. Our objective is to identify and delineate unexplored mechanisms to positively contribute to the vascular biology field and improve treatment strategies. We use multi-disciplinary techniques that include cellular and molecular biology approaches (e.g. aseptic techniques, flow cytometry, PCR, ELISA and others) using patient samples and mouse models to decipher cancer initiation and progression, and the treatment thereof. Lab Website: Ruud P.M. Dings lab website
Pre-requisite courses: No, but Biology, Immunology, and/or Chemistry is desired.
Bioinformatics Students: Yes
Viral and Cellular Determinants of Viral Lymphoma (51UAMS)
Mark Manzano, Ph.D.
COM, Department of Microbiology & Immunology, UAMS
Our laboratory is interested in how viruses cause cancer. We study the Kaposi’s sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi’s sarcoma and primary effusion lymphoma. We are interested in understanding the functions of viral and host genetic factors that control primary effusion lymphoma. Our work utilizes both molecular and cell biology techniques as well as unbiased “omics” approaches (CRISPR screens, genomics, proteomics, metabolomics) to aid us in answering our research questions. Website: https://medicine.uams.edu/mbim/faculty/primary/mark-manzano-ph-d/manzano-lab/
Prerequisite courses – Biology and Chemistry
Bioinformatics students – No
Host Immunity to Bacterial Infections (52UAMS)
Lin-Xi Li, Ph.D.
Department of Microbiology and Immunology, College of Medicine, UAMS
Research in my laboratory focus on understanding the protective T cell and antibody responses against Chlamydia female reproductive tract infection. To track Chlamydia-specific CD4 T cells in vivo, we developed new tools called Chlamydia-specific MHC Class II tetramers that allow for the first time direct visualization of endogenous, antigen-specific CD4 T cells during Chlamydia infection in the mouse FRT. We are also employing a variety of immunological methods, including flow cytometry and immunofluorescence imaging, in conjunction with cellular approaches and gene ablation mouse models to characterize the memory CD4 T cell responses in the FRT during Chlamydia reinfection. In addition, we recently showed that mice lacking B cells experience disseminated Chlamydia infection and develop ascites during Chlamydia primary infection. These unexpected observations lead us to actively seek the precise effector function of host B cells during initial encounter of Chlamydia at the FRT mucosa. We hope that improved understanding of host adaptive immune responses to Chlamydia infection will provide important insights into the rational design of an urgently needed Chlamydia vaccine.
Website: Li Lab Website
Pre-requisite courses: None
Bioinformatics students: Yes
Structural and chemical biology of programmed cell death pathways (53UAMS)
Tudor Moldoveanu, Ph.D.
COM, Department of Biochemistry and Molecular Biology, UAMS
The INBRE summer training program offers the following research opportunities in our lab:
1) Elucidating the structural basis of apoptosis initiation through mitochondrial poration by BCL-2 family proteins. The trainee will learn how to clone, express and purify various BCL-2 proteins, assemble and biophysically characterize their complexes, prepare them for structural biology investigations, and perform structural analyses if time permits.
2) Targeting mitochondrial poration in cancer biology. The trainee will perform steps in structure-based drug design on one of our targets, including drug-based binding and functional assays and structural investigations. She or he will perform these steps iteratively as part of the testing stage of the design-synthesis-testing structure-activity relationship protocol. He or she will work closely with our medicinal chemistry collaborators in Dr. Hong-yu Li laboratory (UAMS Pharmaceutical Sciences).
3) Biotechnological design of novel nano-discs for membrane protein biochemistry and structural biology. The trainee will engineer nano-disc belts to improve their circularization and homogeneity. He or she will learn cloning, expression, purification of newly designed belts and assemble them into nano-discs for downstream analysis, with and without a target membrane protein, by size exclusion chromatography, mass photometry, and electron microscopy.
Pre-requisite courses: None
Bioinformatics students: No
Understanding how microbial exposures and the environment influence heart disease (54UAMS)
Ryan M. Allen, Ph.D.
COM, Department of Physiology and Cell Biology, UAMS
Atherosclerotic cardiovascular diseases (ASCVD) is a progressive disease that develops over several decades and ultimately results in myocardial infarction (heart attack) and stroke. High levels of low-density lipoprotein (LDL) cholesterol are a primary risk factor for ASCVD and pharmacological interventions to lower LDL cholesterol (e.g., statins) have been very successful. However, most heart attack patients now have ‘normal’ cholesterol levels, highlighting missing gaps in our understanding of ASCVD pathogenesis. Chronic, low-grade inflammation is also associated with ASCVD risk, but the molecular mechanisms responsible for this condition have proven elusive. Most recently, we discovered that LDL also transports small pieces of RNA derived from bacteria and other microbes of our environment. When macrophages internalize LDL in the atherosclerotic plaque, this microbial small RNA (sRNA) is released and recognized by toll-like receptor 8 (TLR8), an immune sensor of foreign nucleic acid that activates pro-inflammatory gene programs. Thus, we have identified LDL’s sRNA cargo and TLR8 as novel targets to prevent ASCVD. The goal of my laboratory is to understand how, and from what tissue(s), LDL acquires its microbial sRNA cargo and whether natural changes to LDL-sRNA composition and abundance are correlative with ASCVD. We use a diverse set of techniques ranging from fast-protein liquid chromatography and high-throughput RNA sequencing to in vitro and in vivo models of inflammation and cardiovascular disease.
Pre-requisite courses? No
Bioinformatics students? No
Understanding Molecular Mechanisms of Cell Plasticity in Cardiometabolic Diseases (56UAMS)
Rushita Bagchi, Ph.D.
COM, Department of Physiology and Cell Biology, UAMS
Our lab studies the characteristics and regulation of cell states in health and disease. We use human induced pluripotent stem cells (iPSCs), intact human and mouse tissues, pre-clinical rodent models, and omics platforms to understand the molecular pathways that drive cellular plasticity in cardiovascular and metabolic diseases. We also employ genetic and pharmacological manipulations in cells and mice to investigate how specific genes/proteins may cause cell state transitions, thereby contributing to cardiometabolic diseases. Trainees in the lab can learn and master a variety of techniques, including cell culture (2D and 3D), protein and gene expression assays, DNA-protein and protein-protein interaction assays, cell and tissue imaging techniques, cell behavior assays, animal models of diseases, among others.
Pre-requisite courses: Cell Biology and/or Biochemistry, Physiology recommended
Bioinformatics students: No
Understanding the Pathophysiology of Cardiotoxicity in Response to Chemotherapeutic Agents (57UAMS)
Ashim Bagchi, Ph.D.
COP, Department of Pharmaceutical Sciences, UAMS
Cancer patients who receive chemotherapy often die due to heart failure later in their life. Despite extensive research in this area, we do not fully understand the molecular mechanisms that lead to this condition. Using gene and protein expression assays, in vitro, ex vivo and in vivo model systems of chemotherapy-induced cardiotoxicity, we investigate aspects of mitochondrial and sarcoplasmic reticulum stress. This will improve our understanding of how heart cell toxicity occurs and leads to cardiac dysfunction. Trainees will learn techniques such as qRT-PCR (Quantitative Reverse Transcription PCR), western blotting, live and fixed cells assays for mitochondrial and SR health, and advanced microscopy methods.
Pre-requisite courses: Cell Biology, Biochemistry and/or Physiology recommended.
Bioinformatics students: No
Precision Environmental Health to Tackle High Rates of Early-Onset Breast Cancer in Arkansas Rural Community Health Study (ARCH) (58UAMS)
Ping-Ching Hsu, Ph.D., M.Sc.
Department of Environmental Health Sciences, UAMS
Residents in Arkansas face high risks in generational exposure to pesticides and fertilizers from agricultural production; heavy metals such as arsenic found in the soil, water, air; and aromatic hydrocarbons (benzene, benzo[a]pyrene) from frequent burning of trash, crop and timber residues, and high-temperature cooking. Arkansas Rural Community Health Study (ARCH) is the first and the largest epidemiologic cohort of adult women in AR to examine the effects of both genetic and environmental exposures on an individual’s risk of developing breast cancer (BC) and predicted response to treatment. In total, the institutional-supported ARCH cohort has 26,375 women from all 75 AR counties. In contrast to most cohorts conducted among populations well below average risk, ARCH is enriched with a high rate of early-onset breast cancer (EOBC) cases among all BC prevalent cases at baseline and incident cases when linked with Arkansas Cancer Registry. Given increasing incidence of EOBC nationwide, it is crucial to invest in an understudied rural population with generations of exposure to identify factors responsible for increasing risk and the mechanisms underlying EOBC etiology. Our goal is to maintain, enrich, and enable a broader use of data and sample resources for the ARCH cohort by facilitating longitudinal follow-up since the baseline recruitment 17 years ago. Students will be involved in cohort data (from cancer registry, residential address, follow-up survey) cleaning, support optimizing and documenting the protocol for the detection of environmental chemicals using Inductively-coupled plasma mass spectrometry (ICP-MS), conducting pilot projects comparing trace metals from different bio-specimen (saliva, urine, blood, toenails) using ICP-MS, and to support data analysis on genome-wide DNA methylation profiling. https://uams.info/ARCH
Pre-requisite courses: No, but biology, epidemiology, chemistry is desired.
Bioinformatics students: Yes