To commemorate Women’s History Month and further our mission of helping make research possible, Cayman awarded forty $1,000 research grants. Here are the researchers Cayman is proud to be supporting. Click the links to meet these researchers in: 

Cancer
Cardiovascular System
Cell Biology
Endocrinology & Metabolism
Epigenetics, Transcription, & Translation
Forensic Chemistry & Toxicology
Immunology & Inflammation
Infectious Disease
Neuroscience
Oxidative Stress & Reactive Oxygen Species
Plant Biology

Cancer Research

Laila Ziko, PhD

American University in Cairo

Dr. Ziko is working on finding novel antibacterial and anticancer agents to overcome antibacterial resistance and chemotherapeutic resistance. She is approaching this by examining underexplored prokaryotes for natural compounds with these activities. It is hypothesized that (although the resistance issue is problematic by itself) the COVID-19 pandemic could exacerbate and/or lead to a worse antimicrobial resistance issue in the future. Her preliminary work has found antibacterial and anticancer effects from microbes living in multiple harsh conditions. She plans to use this grant to follow up on these findings by looking for similar activities from underexplored microbes and hopes to eventually establish her own laboratory, supporting scientific discovery in the Middle East North Africa region.

Jiska van der Reest, PhD

Harvard Medical School

Dr. van der Reest is a pre-clinical cancer researcher trained in cancer molecular biology and proteomics/metabolomics. She is interested in understanding how cellular metabolism and redox homeostasis influence each other as both processes are dysregulated in cancer. She developed a technology to measure oxidized proteins in cells and tissues to understand how this contributes to disease and found that metabolic enzymes are particularly sensitive to oxidation, and reciprocal regulation occurs to maintain metabolic and redox homeostasis. She is continuing this work to understand redox-metabolic heterogeneity in the tumor microenvironment. Conventional metabolomics techniques rely on the extraction of metabolites from cells and tissues, which means that the metabolites mix together and thus represent the average profile of the cells in the sample. This causes any spatial information to be lost and makes it impossible to delineate heterogeneity between individual cells. To address this unmet need, she set out to introduce spatiality into metabolomics analyses by developing a platform for single cell tissue metabolomics using mass spectrometry imaging. She is applying this technology to study how tumor and healthy cells interact, in search of new therapies for liver metastatic cancer. She is currently writing a manuscript that describes the technology and demonstrates its advance, so that her approach and protocol can be shared with others in the scientific community for application to a range of biological questions.

Nona Ehyaei, PhD

Michigan State University

Dr. Ehyaei is using structural biology techniques to study the folding of intracellular lipid binding proteins to design new florescent protein tags and to develop rhodopsin mimic systems for mimicking isomerization of rhodopsin proteins. Through investigating the mechanism of wavelength tuning of rhodopsin-mimicked proteins, she has found the photoisomerization of 15-cis to all-trans retinal in a rhodopsin mimicked system. She performed cloning, expression, purification, characterization, and X-ray crystallography on retinol-binding protein II and fatty acid binding protein 5 and studied the ligand binding and formation of domain swapping in this family. She is finishing her dissertation this summer and then plans to join the Moores Cancer Center at UC San Diego Health where she will begin post-doctoral work on cytokines and their effects on cancer growth.

Chang Jiang, PhD

Moffitt Cancer Center

Dr. Jiang's long-term research interest is to understand and delineate molecular networks, which are critical for tumorigenesis, metastasis, and proliferation. She has been focusing on the transcription factor NRF2, specifically on its deregulation in non-small cell lung cancer (NSCLC). Lung cancer remains the leading cause of cancer-related death worldwide, with NSCLC accounting for 85% of all diagnosed lung cancer cases. NSCLC mainly consists of the lung adenocarcinoma or squamous cell carcinoma subtypes. While both of these subtypes have a high frequency of well-defined mutation, such as TP53, KRAS, EGFR, and PIK3CA, they additionally show common and recurrent mutations in the KEAP1/NRF2 circuit (15-34%), leading to the stabilization of the transcription factor NRF2 and the hyperactivation of NRF2 target genes. KEAP1/NRF2 is the primary sensor of oxidative/electrophilic stress. Under normal physiological conditions, NRF2 is constitutively targeted by KEAP1-mediated degradation; however, under oxidative/electrophilic stress conditions, NRF2 is stabilized due to impaired degradation by oxidized KEAP1. In cancer cells, hyperactivation of NRF2 promotes tumorigenesis, progression, and metastasis. Moreover, hyperactivation of NRF2 is associated with poor prognosis due to chemotherapy and radiotherapy resistance. Thus, targeting NRF2 holds great promise for therapeutic development for lung cancer patients. Her research goal is to identify druggable targets to manipulate NRF2 activity and key antioxidant enzymes that mediate the chemoresistance of cells with NRF2/KEAP1 mutations in NSCLC. Ultimately, these studies will shed light on development of therapeutic targets for treatment of NRF2 and KEAP1 mutant NSCLC. She predicts that inhibition of these key antioxidant enzymes will reverse the profound resistance of cells with NRF2/KEAP1 mutations to oxidative stress.

Laura Torrente Fernandez, PhD

Moffitt Cancer Center

Dr. Torrente investigates novel therapeutic venues for NRF2/KEAP1 mutant lung tumors. During her PhD, she characterized the mechanisms by which the stress-responsive kinase HIPK2 potentiates survival of cancer cells under oxidative stress conditions. She discovered a previously unrecognized crosstalk between the transcription factor NRF2 and HIPK2, which synergize to elicit cytoprotective responses in cancer cells, ultimately leading to resistance to therapy.

She is now using her knowledge of the role of oxidative stress in tumorigenesis and chemoresistance as well as the involvement of the NRF2/KEAP1 pathway in a translational project to develop drug studies to identify metabolic and redox vulnerabilities of NRF2/KEAP1 mutant lung tumors. She recently demonstrated that genetic alterations of the NRF2/KEAP1 pathway render lung cancer cells resistant to the anticancer agent β-lapachone via the antioxidant defense. Remarkably, inhibition of superoxide dismutase 1 (SOD1) disrupted the antioxidant capacity and sensitized NRF2 hyperactive cancer cells to β-lapachone exposure. This work was recently published in the journal Redox Biology. Dr. Torrente will use this grant award to continue exploring the therapeutic potential of SOD1 inhibition in lung cancer. Her ultimate research goal is to contribute to the personalization of treatment for lung cancer patients harboring mutations in the NRF2/KEAP1 pathway.

Paloma Gonzalez Sanchez, PhD

Moffitt Cancer Center

Dr. Gonzalez Sanchez is interested in understanding the metabolic interaction between cells. Metabolic communication between different cells and organs is a highly dynamic and complex process in which deregulation of a single step could have consequences for the whole system. In the brain, for example, the metabolic crosstalk between astrocytes and neurons is extremely important, since astrocytes surround the blood vessels in the brain (where nutrients are supplied), and neurons require large amounts of energy to maintain action potentials. The metabolic interaction between these two cell types is essential for the correct function of the brain. Another important example is metabolic reprogramming in cancer cells, where the metabolic phenotype of the tumor depends on direct metabolic communication between cancer and non-cancer cells forming the tumor microenvironment. In the field of cancer, mapping of metabolic interactions is essential to understand the biology underlying tumor development and to design successful therapies. She is starting a new project focused on the metabolic reprogramming in non-small cell lung cancer cells driven by hyperactivation of the antioxidant transcription factor NRF2. She is specially interested in the impact of metabolic reprogramming on the tumor microenvironment. She uses organoids as an in vitro model, examining them for metabolic liabilities by analyzing different enzyme activities, transporters in the plasma membrane, and different metabolic pathways. She will use the funds from this grant to target several metabolic pathways to find one of interest.

Swati Venkat, PhD

Roswell Park Comprehensive Cancer Center

Dr. Venkat's long-term research interests involve elucidating mechanisms by which gene expression alterations contribute to pancreatic cancer. Her academic training and research experience have provided her with a strong background in multiple biological disciplines including biophysics, cell biology, biochemistry, and genomics. Her current post-doctoral training involves understanding the role of 3'-UTR alternative polyadenylation (a highly underappreciated process) in regulating gene expression in pancreatic cancer using a combination of experimental and computational techniques. She is working on a pilot project that involves drug studies measuring protein expression and cell proliferation in pancreatic cancer cells and 3D organoids.

Diane McConnell, DVM, PhD

University of Missouri-Columbia

Dr. McConnell is conducting in vitro studies investigating the role of nicotine and the influence on conventional treatment for the neural tumor glioblastoma. She plans to use this grant to include the use of human tissue to strengthen her hypothesis that the use of nicotine replacement products before and during the treatment for glioblastoma has a negative influence on the effect of conventional therapy. She plans to investigate the expression of the matrix metalloproteinases MMP-2 and MMP-9 in glioblastoma tissues from clinical patients, using available clinical data to correlate the role of these MMPs and the nicotine-use status of the patients with recurrence and overall survival time following diagnosis. MMP-2 and MMP-9 play an important role in degradation of the tissues surrounding a tumor, allowing the tumor cells to migrate and invade. Local invasive growth is a key feature of glioblastoma multiforme and is considered a critical element for the high incidence of recurrence following drastic surgical resection. Nicotine has been implicated in the enhanced activity of MMP-2 and MMP-9 via α-7 nicotinic acetylcholinergic receptors and β-adrenergic receptor pathways in certain cancers. Her work is showing that the use of nicotine-containing products following the diagnosis and treatment of glioblastoma has detrimental effects on treatment efficacy, prognosis, and tumor spread.

Cardiovascular System

Harriet Allan, PhD

Queen Mary University of London

Dr. Allan's research interests center around how platelets change in function and composition as they age within the circulation. Platelets live for approximately ten days within the circulation of a healthy person. However, there are several diseases where there is increased platelet turnover, resulting in a shorter lifespan of between five to seven days. Previous research has shown an association between newly formed platelet levels, platelet hyper-reactivity, and an increased risk of thrombosis. However, research is lacking on the changes that occur during the natural aging process of platelets within the circulation in healthy people. Her research has formed one of the first systematic studies determining changes in differently aged platelets. She has shown that as platelets age there is a loss of mitochondria and cytoskeletal proteins, which may be contributing to the control of platelet lifespan. Mitochondrial biology is well studied in other cell types. However, it has largely been overlooked within platelets. Given the apparent importance of mitochondria during platelet aging, she is working to understand how mitochondrial dynamics may be contributing to both platelet aging and reactivity. Preliminary data suggests that during activation, platelets expel their mitochondria encapsulated within microvesicles, which can affect the phenotype of other blood cells. She plans to use these grant funds to obtain more data towards this study.

Carmen De Miguel, PhD

University of Alabama at Birmingham

Dr. De Miguel is interested in how the immune system leads to kidney disease in diabetes and hypertension. She is studying the role of endothelin in hypertension-mediated inflammation and end-organ damage. She also is involved in integrating novel mechanisms controlling diabetic kidney disease. She works with undergraduate students from underserved communities and plans to use the grant to buy ELISA plates for these minority students to measure different markers of inflammation in the kidney during diabetes, giving them the opportunity to do research in a real biomedical laboratory studying pathways with a high impact in human disease.

Shea Sickles

University of Kentucky

Ms. Sickles' work focuses on developmental programming of offspring of preeclamptic nonhuman primate mothers. She is exploring impaired renal and metabolic function of these offspring. The Jeffrey Osborn lab where she is receiving her graduate training has recently discovered that the African Green Monkey develops spontaneous gestational hypertension as well as postpartum hypertension. As hypertensive pregnancy disorders are a leading cause of maternal mortality worldwide, with 99% of maternal deaths occurring in developing countries, a model similar to humans is critical to translational research. This grant will help her embark on her first year of research.

Cell Biology

Elizabeth Delorme-Axford, PhD

Oakland University

Dr. Delorme-Axford's current work focuses on identifying the molecular mechanisms regulating cellular autophagy in the model organism Saccharomyces cerevisiae. Autophagy is a highly conserved process of cellular 'self-eating' in which aged organelles, ubiquitinated cargo, and protein aggregates are targeted for degradation in the lysosomes (in mammals) or vacuole (in yeast). Notably, aberrant autophagy is associated with diverse human pathologies such as cancer, neurodegenerative diseases, and lysosomal storage disorders. She is actively working to complete experiments related to two manuscripts that are currently in preparation. For one of the manuscripts, she is investigating metabolic regulation and autophagy. These studies will provide further evidence for how cellular metabolic networks influence autophagy activity. In the fall of 2020, she will launch her independent research program at Oakland University in Rochester, MI.

Endocrinology & Metabolism

Carla Madelaire, PhD

Northern Arizona University

Dr. Madelaire's postdoctoral research focuses on how reproductive and stress hormones can affect immunity and other aspects of animal physiology. She studies animals in different ecological contexts, including animal invasion, survival in extreme environments, reproduction, thermal regulation, and response to stress protocols, among others. Currently she is standardizing hormone measures in non-traditional samples such as saliva from toads submitted to stress protocols, Peruvian mummy bones from different eras, and squirrel feces collected in different seasons.

Carley Lowe

Northern Arizona University

As a graduate student, Ms. Lowe is interested in assessing stress and reproduction in large whales and coming up with novel ways to overcome the logistical challenges of sampling whales that live the entirety of their lives underwater, often far from shore, and that travel up to 10,000 miles per year. She has access to many plates of baleen (the long tooth-like structure that grows from a whale's upper jaw) and has been successful in using these plates to look at a time series of stress and reproductive hormones as the whale ages. She next plans to examine contaminants along the baleen plate, including mercury. She will use the grant funds to conduct mercury analysis in 12 plates of baleen to see the contaminant loads in different ages and sexes of humpback whales.

Nerea Alonso, PhD

University of Edinburgh

Dr. Alonso studies bone metabolism and disease, focusing on the identification of genetic markers for bone diseases like osteoporosis and Paget's disease, as well as investigating the genetic background of rare bone diseases like osteoporosis pseudoglioma syndrome and hypophosphatasia. She is interested in the functional evaluation of the genetic targets identified by high-throughput data like GWAS, using in vitro and in vivo models of bone metabolism. She is especially interested in the pharmacogenomics of osteoporosis, investigating markers associated with the response to treatment and has collected data showing the importance of lipid metabolism in the development of osteoporosis. She would like to understand the link between bone and lipids to identify novel targets to develop personalized treatment approaches for patients with the disease. Patients with osteoporosis are given a range of treatments to prevent or reduce the risk of fracture. However, in some cases, the patients do not respond well to the treatment and continue to lose bone mass, which is associated with an increase in their morbidity and mortality. She is investigating the role of lipid metabolism in osteoblasts in the response to treatment with an osteoporotic drug. Understanding the role of these molecules will help to modulate them to improve the response to treatment. This grant will help her continue this research.

Renata Whitton, PhD

University of São Paulo

Dr. Whitton studies fish endocrinology and works in comparative physiology, within the sub-areas of fish metabolism and endocrinology with application in fish farming and aquatic ecotoxicology. She is researching lipid and fatty acid metabolism, gonadal steroids, gonadotropins, the effects of pollutants on the reproductive physiology of fish, and physiology projects applied to the cultivation of tropical fish. She also studies marine fish, mainly the serranid group, with morpho-physiological aspects of hermaphroditism, induced reproduction, and larval development. This grant will help fund her research to understand the impacts of climate and environmental changes on fish.

Stefanny Titon, PhD

University of São Paulo

Dr. Titon works in the fields of endocrinology and comparative immunology with anurans, a class of amphibians that includes frogs and toads. She is mainly focused on understanding the acute and chronic stress effects on the hormonal and immune response in anurans. She is also seeking to determine the relationship among hormonal balance, immune response, and body index under stress conditions in these animals. Stressors can increase plasma glucocorticoid levels and decrease plasma androgen levels in different species. Glucocorticoids can have immune-enhancing or immunosuppressive effects, which are dependent upon stress duration and intensity. The worldwide decline in amphibian populations is strongly linked to an array of different stressors. The impacts of stress on glucocorticoids, androgens, and the immune response are important to clarify and should lead to the better development of conservation strategies.

Friederike Pohlin, MRCVS, DVM, MSc, PhD

University of Veterinary Medicine Vienna

Dr. Pohlin's research interests include the improvement of wildlife anesthesia and wildlife management techniques, the impact of wildlife trafficking on animal welfare, and ecophysiological adaptations of wild animals to the changing climate. She is studying the measurement of stress and other physiological responses, from a clinical pathology point of view, in translocated rhinoceroses. Many rhinoceroses get sick and die after long road transport, and it is therefore crucial to increase the understanding of the pathophysiological processes associated with translocation in order to save the species.

Stefanie U. Wetzels, PhD

University of Veterinary Medicine Vienna

Dr. Wetzels researches the microbiome of the gastrointestinal tract of animals and microbial contamination during slaughter and food processing. Her studies cover a huge range of topics, including rumen microbiota, wildlife, small animal, and human microbiomes, as well as hygiene in meat and milk production. She is currently working to publish results to help demonstrate the link between stress reaction and the microbiome in relation to the high death rates observed when transporting rhinoceroses. Her group's results give hints to the differences in gut microbial diversity and composition in white rhinoceroses (Ceratotherium simum) of different age and sex, and the effect of capture and long road transport by monitoring fecal samples before and after a 30 hour transport to detect shifts in the composition of the fecal microbiota via 16S rRNA gene MiSeq amplicon sequencing. A strong shift on phylum level occurs with a statistically significant decrease in Bacteroidetes and a statistically significant increase in Proteobacteria and Actinobacteria. The high abundance of Clostridia in the fecal samples is also noted specifically regarding the diarrhea rhinoceroses often suffer from during and after transport.

Epigenetics, Transcription, & Translation

Ana-Maria Raicu

Michigan State University

Ms. Raicu's research interests lie in understanding gene regulation and how transcriptional co-repressor proteins impact chromatin to turn off gene expression. The Arnosti lab where she is receiving her PhD training studies gene expression in a developmental and evolutionary context using the fruit fly. They study the retinoblastoma tumor suppressor protein (Rb) and have looked at the biochemistry behind how it functions and investigated various residues and domains that are important for its regulation and repressive potential. They have also conducted 'omics studies to uncover the differences between Rb paralogs in the fly, the kinds of gene promoters they bind to, and their preferential binding on the genome. She is focusing her dissertation work on understanding the Rb protein family and uncovering both mechanistic and biochemical activities of Rb proteins, making comparisons with other conserved transcriptional corepressor proteins like CtBP. She is making use of a modified CRISPR system in which she has created dCas9 fusions to Rb to deploy them to any site on the Drosophila genome. This dCas9-mediated recruitment of Rb allows her to study their impact on chromatin and gene expression at particular target sites and make comparisons between the paralogs. She plans to couple local, mechanistic studies with biochemical studies using mass spectrometry to understand differences in Rb binding partners. The goal is to gain a better understanding of the significance of the diversification of the Rb family and to also learn more about mechanisms of transcriptional repression throughout development. 

Forensic Chemistry & Toxicology

Annelies Cannaert, PhD

Ghent University

Dr. Cannaert's research mainly focuses on new psychoactive substances (NPS). She helped to develop a novel concept in the field of forensic toxicology: the activity-based detection of NPS as an alternative 'untargeted' screening approach. The emergence of NPS in recent years has brought along an explosive growth in a new segment of the illegal drug market. NPS are typically created by modifying the chemical structure of illegal drugs or prescribed medications, to generate substances that are not covered by international drug controls. She is focusing on synthetic cannabinoid receptor agonists and synthetic opioids, screening for their activity in biological matrices by monitoring receptor activation. The receptor activation reporter assays she has developed are being successfully applied on biological matrices as an untargeted screening strategy and are used as tools to assess the potency of newly emerging substances. The information she is gathering will play a key role in creating new state-of-the-art reports and publications concerning newly emerging drugs, generating essential data on their potency and toxicity that can be used in the interest of public services.

Eline Pottie

Ghent University

Ms. Pottie's research interests are mainly focused on G-protein coupled receptor (GPCR) bioassays, employed for the functional characterization of chemical compounds. She is using these assays to determine the potency and efficacy of scarcely characterized new psychoactive substances (NPS)—compounds that mimic the effects of the traditional illicit drugs but are structurally distinct from them. As these compounds emerge at rapid pace, they are, and often remain, poorly characterized in terms of their pharmacological and toxicological effects. She has developed several bioassays monitoring the activation of the serotonin 2A (5-HT_2A) receptor, which are being used for the functional characterization of hallucinogenic NPS, enabling assessment of their structure-activity relationship and their potentially biased agonism. This latter phenomenon implies the preferential activation of one (or a subset of) signaling pathway(s) upon agonist binding to the receptor. Analogous to this application, bioassays have also been developed to monitor the activation of the A₃ adenosine receptor to determine the potency and efficacy of newly synthesized agonists and their potentially biased agonism. Her work is important for the pharmacological characterization of substances active at the 5-HT_2AR to provide more information on NPS that will be valuable to the scientific community in both pharmacology and toxicology fields.

Marthe Vandeputte

Ghent University

Ms. Vandeputte's research mainly focuses on novel approaches for the pharmacological characterization and detection of new psychoactive substances (NPS), particularly synthetic opioids and synthetic cannabinoid receptor agonists. With the appearance of over 730 NPS in Europe since 1997, the last two decades have seen a dynamic growth in the availability and use of NPS across the globe. As the seemingly endless chemical diversity of these often very potent, novel abused substances hampers their easy monitoring, unique tools have been developed in the lab where she is receiving her PhD training that allow the activity-based detection of these substances. By monitoring in vitro receptor activation of synthetic cannabinoids (via cannabinoid receptors 1/2) or opioids (via the μ-opioid receptor) in biological matrices, they can detect the presence of these drugs without prior knowledge of their structure, or even their existence. She is seeking to further improve and strengthen this activity-based screening strategy by combining the different existing assays into one universal bioassay allowing the detection of different classes of NPS at once. In addition, these bioassays are also used as a tool for the pharmacological profiling of newly emerging substances. As new drugs appear on the illicit drug market, she hopes to continue the pharmacological profiling of such substances to help eliminate the potential danger their use might bring along. 

Caitlyn Norman

University of Dundee

Ms. Norman's research focuses on the detection, quantitation, and evaluation of new psychoactive substances (NPS) used in prisons. Her work aims to reduce the supply of NPS, reduce harm to prisoners, and study the potential for secondary exposure to prison staff. The use of NPS in prisons is a global problem, but with the constantly evolving market, there is often little intelligence around the actual compounds being used, in what concentrations, and in which mixtures. She is using a qualitative and quantitative method for the detection of NPS on infused papers seized from prisons. This work demonstrated the utility of testing non-judicial samples for near real-time monitoring and intelligence purposes. The information is being used to study the pharmacology and pharmacokinetics of relevant compounds and to predict and test the compounds likely to appear next. She is also evaluating the selectivity and sensitivity of the ion mobility spectrometers that UK prisons use to scan incoming mail and material circulating within the prison to detect NPS-infused papers. The potential for secondary exposure of NPS through transdermal absorption and passive smoking from e-cigarettes is also being explored, since it has been reported that prison staff have fallen ill, likely due to secondary exposure to NPS. It is important to understand the potential routes of secondary exposure to these compounds in order to understand the circumstances that make prison staff vulnerable and determine safety measures that can be taken in order to effectively protect the prison staff and other prisoners.

Immunology & Inflammation

Luiza Oliveira Perucci, PhD

Federal University of Ouro Preto

Dr. Oliveira Perucci's research is focused on the immunoregulatory mechanisms of human inflammatory diseases—mainly preeclampsia, a disease that has no cure, affects 3-10% of pregnancies worldwide, and is associated with several maternal and fetal/neonatal complications. She studies the role of lipid inflammatory mediators (specialized pro-resolving lipid mediators; SPMs) like lipoxin A₄, resolvin D1 and maresin 1 derived from ω-3 and ω-6 fatty acids. Recent data indicate that these mediators act as brakes for the inflammatory response, so they may serve as novel targets in preeclampsia. Her research group is performing a longitudinal study with Brazilian pregnant women with risk factors for the development of preeclampsia to evaluate the levels of inflammatory mediators, such as SPMs, through immunoassays. Although preeclampsia diagnoses occur after 20 weeks of gestation, the disease dysfunctions begin early in pregnancy. As preeclamptic women have several immune alterations leading to an overwhelming inflammatory response that is associated with the disease manifestations, she expects altered levels of lipid mediators that have anti-inflammatory and pro-resolving actions in women who are destined to develop the disease. If this happens, SPMs could be used in the future as early biomarkers or targets to novel therapies for preeclampsia.

Samanta Funes, PhD

Multidisciplinary Institute of Biological Research-San Luis

Dr. Funes' research interests have been focused on autoimmune conditions, their mechanisms of progression, and the development of novel therapies tending to improve a patient´s life quality. She has studied the humoral immune response in an experimental model of autoimmune neuropathy (Guillain-Barré syndrome) and the innate immune response in reactive arthritis and systemic lupus erythematosus. She recently published data showing the therapeutic potential of transferring tolerogenic dendritic cells generated with heme‐oxygenase inductor cobalt (III) protoporphyrin IX, dexamethasone, and rosiglitazone for systemic autoimmunity. Her current research plan proposes to study the immunotherapeutic role of antidepressants as a new strategy to improve autoimmune rheumatic diseases and plans to use this grant to help fund the costs of this research.

Kara Rood, MD

The Ohio State University Wexner Medical Center

Dr. Rood's research interests are around preeclampsia, a maternal complication affecting ~5-8% of pregnancies. Preeclampsia is a multifaceted syndrome arising after 20 weeks' gestation characterized by new onset hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg on two separate occasions), proteinuria (>300 mg/24-hour collection) that often involves endothelial cell dysfunction, and end-organ damage. She is investigating the role of aspirin for preeclampsia prevention and its possible mechanism of action through initiation of lipid class switching from pro-inflammatory to anti-inflammatory/pro-resolving mediators that restore normal maternal endothelial cell function and prevent onset of the disease. This grant will aid with further examining the role of aspirin-induced lipid class switching from pro-inflammatory to anti-inflammatory/pro-resolving mediators in endothelial cells and trophoblasts.

Merran Dunford

University of Bath

Ms. Dunford studies inflammatory bowel disease (IBD), a debilitating, poorly controlled disease affecting 1.3% of US adults (3 million). IBD remains a significant unmet medical need, with most patients ultimately submitting to surgery for removal of their entire colon. The best current treatment agents, such as anti-TNF-α therapies, come with black box warnings due to potential catastrophic infections and yet only benefit a subset of patients. She is focusing on defining how the balance of pro- and anti-inflammatory lipids in the colon has become disrupted with IBD. Recent data points to the role of hepoxilin A₃ (HxA₃) and the N-acylethanolamine (NAE) family of endocannabinoids in regulating the state of intestinal inflammation. Her research involves measuring the levels of these and associated bioactive lipids that have been shown to be regulated in IBD in rodent models of intestinal inflammation in a manner that can be correlated with disease status and microbiome properties. She is collaborating with a gastrointestinal surgeon to obtain samples from resected tissues obtained at scheduled surgeries. Using these samples, she is comparing the levels of these regulatory lipids in tissues from IBD patients (and healthy controls collected as clean edges from colorectal cancer resections) with information collected from rodent models of inflammation. Preliminary data show higher levels of HxA₃ in inflamed tissues, while levels of NAEs show a decrease. The ability to measure and correlate HxA₃ and NAEs levels with inflammatory status provides the first-ever possibility to monitor and understand the processes of remission and relapse in the inflammatory diseases related to these lipids. Understanding the balance of HxA₃ and NAEs lipid levels as they relate to inflammatory status will provide clinical hallmarks that could be used to identify new biomarkers for early diagnosis of IBD. Her goal is to identify strategies to treat IBD through rational modulation of regulatory lipids within the intestinal lumen, possibly identifying safer and more effective drug treatments for IBD. Her work is also helping to improve the understanding of epithelial cell structure and function in health and disease, which is important for the delivery of pharmaceuticals across the intestinal barrier.

Jennifer Speth, PhD

University of Michigan

Dr. Speth studies the role of alveolar macrophages in lung diseases such as lung cancer as well as allergic asthma and aging. She is particularly focused on understanding the role of prostaglandin E₂ in the regulation of alveolar macrophage function in these diseases. Although the alveolar macrophages comprise the major resident immune cell in the lung, few studies have investigated their role in lung cancer development. Her group recently discovered a potentially novel mechanism wherein alveolar macrophages regulate STAT-induced inflammatory responses in neighboring epithelial cells through secretion and delivery of suppressors of cytokine signaling 3 (SOCS3) within extracellular vesicles. She is exploring the impact of SOCS3 transfer on epithelial cell tumorigenesis and alveolar macrophage SOCS3 secretion during the development of lung cancer. Her work has identified alveolar macrophage-derived vesicular SOCS3 as an endogenous antitumor mechanism that is disrupted within the tumor microenvironment. She has shown that rescue by synthetic liposomes can be leveraged as a potential therapeutic strategy for lung cancer.

Antonia Rotolo, MD, PhD

University of Pennsylvania

Dr. Rotolo's research focuses on invariant natural killer T cells (iNKT) and gene-engineered adoptive cell therapies that can be translated into the oncology clinic. Part of her post-doctoral training was with Dr. Carl June's team at University of Pennsylvania, where the first FDA-approved CAR-T therapeutics were developed. She is currently a postdoctoral fellow under the mentorship of Dr. Nicola Mason at the School of Veterinary Medicine at University of Pennsylvania. They are planning to conduct the first iNKT and CAR-iNKT clinical trials in dogs with naturally occurring solid cancers. These will serve as a bridge to accelerate translation of 'off-the-shelf', allogeneic iNKT/CAR-iNKT therapies to the human clinics. Dogs have an intact immune system with remarkable homology to that of humans, and diagnostic tests, treatments, and management for canine and human cancers are very similar. Thus, her model system provides an invaluable opportunity for research that simultaneously helps improve both canine and human health care.

Tina Sumpter, PhD

University of Pittsburgh

Dr. Sumpter's research goal is to develop clinically applicable platforms that exploit the cutaneous immune system to better treat human disease. To reach this end, the objectives of her lab are to understand mechanisms that facilitate the transition between immunological regulation and activation in the skin and to understand the link between innate immune cells in the skin and systemic immune responses. Her group is specifically focused on cutaneous mast cells and regulatory pathways that hold these cells in check and in exploiting these pathways to develop better therapeutics for patients with allergic disease. She is planning to use this grant funding to finish preparing a manuscript of a study investigating the therapeutic potential of immunoresolvins, such as lipoxin A₄, in the skin. A second study evaluating glyburide in allergy is also underway.

Infectious Disease

Christine Arbour, PhD

Massachusetts Institute of Technology

Dr. Arbour's research goals are to design and synthesize effective uridine-based inhibitors to target monotopic phosphoglycosyl transferases (PGTs). PGTs are responsible for catalyzing the first membrane-committed step in the synthesis of complex glycan products associated with bacterial virulence. Specifically, PGTs are involved in the initial step of bacterial glycosylation biosynthesis by transferring a phospho-sugar from a uridine diphosphate-sugar (UDP-sugar) to membrane-bound undecaprenol phosphate. Nucleoside-based small molecules are excellent scaffolds for inhibiting PGTs, because they structurally mimic the phospho-sugar donor, UDP-sugar. She is collecting compounds to create a uridine-containing small molecule inhibitor library that will be tested for activity against PGTs, which will lead to a publication and ultimately demonstrate its potential for antibiotic applications.

Margaret Nolan, PhD

Stellenbosch University

Dr. Nolan uses animal models of basic immune mechanisms to study vaccine response to Mycobacterium tuberculosis using Mycobacterium bovis bacillus Calmette–Guérin (BCG), the only vaccine approved for use to prevent tuberculosis (TB). Her work aims to improve the vaccine strategy for prevention of TB, a disease that in 2018 killed over one million people and remains a leading cause of death globally. She is focusing on hematopoietic stem cells and their role in trained immunity. Her previous work involved the development of a novel recombinant zona pellucida immunocontraceptive vaccine for domestic and wildlife species. This grant will help fund training in data analysis techniques including whole transcriptome sequencing, chromatin immunoprecipitation sequencing, and assaying for transposase-accessible chromatin using sequencing. It is imperative that advances are made in mechanistic research to understand the complexity of the immune response surrounding TB to eradicate this deadly disease.

Adela Cota-Gomez, PhD

University of Colorado Anschutz Medical Campus

Dr. Cota-Gomez works on the molecular and cellular mechanisms leading to pulmonary complications that arise in patients with long-term HIV infection. Her work has contributed to defining mechanisms of lung damage by HIV, which include inflammation, oxidative stress, and alterations of the lung microbiome. Her group has defined some of the multiple functions of the HIV proteins, Tat and Nef, in development of pulmonary complications such as pulmonary arterial hypertension (PAH). These two "accessory" proteins have important direct roles in the viral life cycle but also can re-direct cellular processes in uninfected cells. Soluble forms of these proteins can activate cell-adhesion molecule expression, inflammatory responses, apoptosis, and cell proliferation, all through the induction of oxidative stress. Understanding the mechanisms by which these viral proteins interfere with these cellular processes is essential to successful interventions to limit the damage caused by inflammation, apoptosis, and hyperproliferation, which are central to PAH pathogenesis. She very recently has forged collaborations with colleagues to conduct SARS-CoV-2 research and is gathering essential preliminary data that this grant will help to support.

Marcella Sharma

Wayne State University

Ms. Sharma works in antimicrobial drug discovery, focusing on novel drug targets. Novel antimicrobial development is an area of great importance due to the rise in antimicrobial resistance. The drug targets that the lab, where she is receiving graduate training, focuses on are the microbial enzymes PurE and PurK from the de novo purine biosynthesis pathway as well as bacterial folate biosynthesis enzymes. She is using novel assays and high-throughput screening to identify inhibitors of these enzymes that will help direct fragment-based drug design.

Neuroscience

Aurélie de Rus Jacquet, PhD

Laval University

Dr. de Rus Jacquet is an ethnopharmacologist specializing in the study of Parkinson's disease. Her research documents the traditional uses of neuroprotective plants in remote areas of the world and tests their pro-health effects in cellular models of Parkinson's disease. She discovered that a subset of botanical extracts mitigates the loss of dopaminergic neurons and potentiates the neuroprotective role of astrocytes. Using primary and iPSC-derived models of Parkinson's disease, she is investigating the role of astrocytes in disease onset and progression. Defining the neuroprotective and neurotoxic effects of astrocytes will guide new drug screening strategies, including the screening of her collection of traditionally used botanical extracts. Her research proposes an innovative drug discovery approach: to document traditional medicines used to treat Parkinson's disease and screen these plants for their neuroprotective potential. She has already identified several promising candidates.

Swetha Gowrishankar, PhD

University of Illinois at Chicago

Dr. Gowrishankar is working to understand the molecular mechanisms underlying the association of altered lysosome function with numerous neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease, and hereditary spastic paraplegia (HSP). The function of lysosomes to degrade organelles is critical for protecting long-lived cells such as neurons from the buildup of misfolded proteins and damaged organelles. Her post-doctoral work investigating the cell biology of amyloid plaques in AD led to the discovery of an unexpected heterogeneity of neuronal lysosomes. Unlike lysosomes in neuronal cell bodies, those in neurites lack luminal proteases needed for degradation. She found that perturbing transport (and maturation) of the axonal pool specifically exacerbated AD plaque pathology. Now as an independent investigator, she is working to understand how these distinct lysosomal pools form, interact, and function in different parts of the neuron and how their dysfunction causes and/or exacerbates neurodegenerative diseases. Using a multidisciplinary approach (imaging, proteomics, and Cas9-mediated perturbation in neurons), her group is identifying the defining molecular composition of these distinct lysosomal populations, factors that uniquely (or differentially) regulate them, the molecular basis for their differential responses to stresses, and mechanisms underlying lysosome dysfunction in AD and HSP.

Oxidative Stress & Reactive Oxygen Species

Tinna Traustadóttir, PhD

Northern Arizona University

Dr. Traustadóttir studies the redox biology of aging. Her lab focuses on three research aims to determine: 1) the mechanisms of diminished resistance to oxidative stress with aging and plasticity of redox signaling pathways; 2) the efficacy of interventions such as exercise and phytonutrients in preventing or attenuating these age-related changes in redox signaling; and 3) the effects of different exercise protocols (modes, intensity, and volume) on redox signaling and resistance to oxidative stress. She plans to use this grant to help students in her lab with projects that are not currently funded, to pay for supplies and assay kits. 

Maria Fedorova, PhD

Leipzig University

Dr. Fedorova's research is aimed at the development and application of mass spectrometry-based methods for analysis of protein and lipid modifications, including lipid-protein adducts. She is working to understand the role of redox lipid and protein signaling in the onset and progression of human disorders associated with chronic inflammation, including cardiovascular and metabolic diseases. Chronic inflammation is closely associated with the dysregulation of the production and elimination of various reactive oxygen and nitrogen species leading to the alteration of cellular signaling pathways, biomolecule modifications, and turnover. Redox disbalance can affect proteins, lipids, metabolites, and nucleic acids. The main challenge in the identification of modified species, which is necessary to understand mechanisms of their toxicity and biological activities, is their low in vivo abundance as well as high chemical diversity, which requires sophisticated bioanalytical solutions. Her research combines the development and application of new high-throughput bioanalytical techniques for analysis of native and modified proteins and lipids using cellular models of oxidative stress and inflammation as well as clinical samples with application of bioinformatics and systems biology/medicine tools to uncover the biomedical consequences of redox disbalance. She is planning new experiments to establish a new high-throughput LC-MS/MS-based epilipidomics platform for systems-wide identification of oxidized lipids along several classes in a semi-targeted way with a goal to understand the epilipidomics signature of metabolic disorders and ferroptotic cell death.

Plant Biology

Georgina Fabro, PhD

National University of Córdoba

Dr. Fabro studies plant pathogen interactions and effectors. Different phytopathogens such as bacteria, fungi, and oomycetes that feed on plants use a variety of molecules to colonize their hosts. Effector proteins, which are secreted by pathogens and delivered into plant cells, play pivotal roles in establishing a successful infection. The detailed study of the activities exhibited by phytopathogen effectors is of great relevance for the generation of knowledge that allows improvement of crop resistance to pests, as well as to manipulate the biochemistry and the development of the plants in the absence of disease. She is seeking to understand the function of the effectors in order to modify the transport of components to subcellular or extracellular domains, alter hormonal balances to promote growth, and activate the transcription of specific defense genes in response to the perception of conserved pathogenic molecules. A limitation for this type of application is that very little is known about the roles of effectors themselves as well as the identities of their target proteins in the host cell and also the functions exerted by those targets when alone/modified by the effector. She is working to characterize the roles of RxLR effector proteins from the oomycete model pathogen Hyaloperonospora arabidopsidis (Hpa) and their orthologs from Phytophthora infestans as well as effectors from the fungus Golovinomyces orontii in regulating plant defense systems and their growth and development programs.