Year in Program: 2nd

Hometown: Abidjan, Ivory Coast

Mentor: Dr. Naren

Email: amoakoja@mail.uc.edu

Year in Program: 5th

Hometown: Taiyuan, China

Mentors: Drs. Hong and Zhang

Email:
caoyh@mail.uc.edu

My interests are determining the roles of circadian rhythms in: 1. regeneration of intestinal stem cells (ISCs) via mTOR signaling, and 2. cell proliferation and tumor development via regulation of Wnt, p53 and Apc.

1. Mammalian Target of Rapamycin Complex 1 (mTORC1) is the central core of anabolic metabolism, by surrounding hormone and growth factor signal to direct synthesis of macromolecules, including DNA, ribosome (rRNA and protein) and lipid. Previous studies showed that mTORC1 is fundamental in ISC maintenance and is increased upon Bmal1 disruption both in vivo and in mouse lung fibroblast. Other publications showed that general inhibition of mTORC1 is not sufficient in cancer therapy, so that deeper study downstream of mTORC1 signaling and temporal inhibition is required. However, the role of circadian rhythms in ISC regeneration via mTOR signaling remains unknown.

Circadian rhythms strongly influence intestinal crypt physiology, including cell cycle, cell proliferation, and ISC regeneration. For cell cycle, a few of the molecular connections of intracellular coupling were uncovered, and our group recently identified a mechanism of circadian rhythm and cell cycle coupling that expanded to the intercellular level via Wnt signaling between Paneth cells and ISCs (Matsu-Ura, T. et al.). In addition, the key components of proliferation (e.g. Wnt, Kras, c-Myc, Apc) show circadian rhythms, and previous reports showed that overexpression of circadian genes (e.g. Bmal1) increases the efficiency of chemotherapy in cancer treatment, which indicates that circadian rhythm is highly associated with cell proliferation and tumor development. However the molecular mechanisms connecting circadian rhythm with cell cycle, cell proliferation, and tumor development remain largely unknown.

Interests after work: cooking, painting, and traveling

Year in Program: 5th

Hometown: Cincinnati, Ohio

Mentors: Drs. DeMazumder and Kranias

Email:
crockejy@mail.uc.edu

Social Chair, Physiology Student Organization
NIH National Research Service Award (F31)

Sudden cardiac death (SCD) from ventricular arrhythmias claims more lives every year than cancer, diabetes, and all other pathological diseases combined. This is chiefly due to a lack of understanding how SCD manifests (i.e. the underlying mechanisms are unclear), preventing development of newer, more effective therapies. An additional problem is the lack of suitable animal models which mimic the disease as in their human counterparts. The DeMazumder lab has developed a novel guinea pig model of SCD, which allows us to address previously unanswered questions surrounding the mechanisms of sudden death.

People with heart failure (HF) are at the greatest risk of SCD. More than half of the deaths in HF patients are the result of SCD. Currently, there are no suitable treatments to prevent or cure SCD and HF. Therapies in use are palliative and only serve to address symptoms and do not reverse disease progression. Chronic vagus nerve stimulation (VNS), commonly used for treatment in various neurological disorders (e.g. epilepsy), is being clinically evaluated as an exciting new therapy for HF and has been shown to improve ventricular function in HF patients. However, results are conflicting across trials. This is most likely attributed to differences in the empirically selected stimulation parameters and durations. Though chronic VNS is currently being studied as a potential HF therapy, chronic VNS has not yet been studied in the context of SCD. Previous studies conducted by the DeMazumder lab show that activation of the parasympathetic nervous pathway improves cardiac function in HF and reduces SCD incidence. While the effects of acute VNS are well documented, not much is known about the effects of chronic VNS. Studies conducted over 150 years ago by Einbrodt show that acute VNS is capable of abolishing arrhythmia; however, chronic VNS may increase SCD risk by modulating cardiac electrical activity, which is already impacted in HF. However, preliminary data from our lab show that although chronic VNS does impact the heart's electrical properties, it serves to stabilize the heart's natural rhythm, decreasing risk of arrhythmia and abolishing SCD completely in our animal models. Our lab's current objective is to elucidate the underlying pathways and mechanisms linking SCD, HF, and chronic VNS. In doing so, we hope to: (1) improve upon current usage of VNS in HF; (2) apply chronic VNS as a suitable therapy for SCD; and (3) design new therapies that target these understudied pathways of SCD and HF.

My project investigates autonomic sensitivity and response across several animal models incorporating SCD, HF, and chronic VNS. Autonomic dysfunction and remodeling are hallmarks of both SCD and HF. Changes in the way the body responds to natural stressors over time leads to alterations in autonomic nervous signaling cascades and cardiac response. These changes impact how the heart functions (e.g. decreasing the heart's ability to pump blood and oxygenate the body effectively, which in turn increases the heart's workload). By studying how the heart's electrophysiological properties differ in SCD and HF as compared to normal, healthy hearts, we are able to evaluate which steps of the underlying mechanisms to target for development of future therapies for the prevention of SCD.

Year in Program: 5th

Hometown: Brooklyn, New York

Mentor: Dr. Zavros

Email:
duaawemb@mail.uc.edu

Albert C. Yates Fellow
Graduate Student Research Forum 2019, Honorable Mention, UC College of Medicine

Prevalence of gastric ulcers increases in the elderly, yet the cause of the age-associated escalation is unknown. My long-term goal is to understand not only the process of gastric epithelial repair in response to injury, but the mechanism by which abnormal regeneration influences the incidence of H. pylori-associated disease in the elderly. Chronic inflammation induced by H. pylori infection results in epithelial cell death and damage to the stomach lining, also known as a gastric ulcer.  H. pylori is known to adhere to the gastric epithelium through the binding of bacterial adhesins BabA and SabA to glycosylated receptors Lewis B and sialyl-Lewis X (S-LewX) expressed on epithelial cells.  Recent studies have revealed that H. pylori localizes specifically to Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands within the corpus of the stomach.  SPEM has been demonstrated to arise from oxyntic atrophy followed by transdifferentiation of mature chief cells by inflammation and is marked by the expression of Cluster-of-differentiation gene 44 (CD44). CD44 is known to coordinate normal and metaplastic epithelial cell proliferation and CD44 variant isoform 9 (CD44v9) is expressed in gastric cancer stem cells. Our group has reported that CD44v9 is co-expressed with markers of SPEM, a reparative phenotype that emerges in response to gastric injury.  Our preliminary data suggest that regeneration of the aged gastric epithelium post-injury exhibits uncontrolled SPEM expression that expresses both CD44v9 and S-LewX. Our central hypothesis is that the regenerative process of the aged gastric epithelium is impaired in response to injury, such that an expansion of S-LewX expression on abnormally regenerating glands results in increased susceptibility to H. pylori colonization and disease progression. To analyze cellular and functional changes of the aging gastric epithelium and H. pylori-induced disease progression after regeneration in response to gastric injury, we use an acetic acid-induced injury model and in vivo H. pylori adherence assays in young (2-3 months) and aged (>8 months) mice and in young (15 weeks) and aged (9-12 months) Mongolian gerbils. Additionally, gastric organoids derived from young (14-30 years) or elderly (>55 years) patients are generated and transferred to a monolayer culture for in vivo H. pylori adherence assays to analyze acid secretion and cellular composition in human gastric epithelium. My long-term goal is to define age-related modifications to the gastric epithelium and determine how these changes influence incidence of H. pylori-associated disease in the elderly.

Publications, Complete List at PubMed

Year in Program: 2nd

Hometown: Cincinnati, Ohio

Mentor: Dr. Herman

Email: gloriuac@mail.uc.edu

Year in Program: 3rd

Hometown: Istanbul, Turkey

Mentor: Dr. Hong

Email: gokerse@mail.uc.edu

Publications, Complete List at PubMed

Year in Program: 4th

Hometown: Kuala Lumpur, Malaysia

Mentor: Dr. Hogenesch

Email:
lee2yy@mail.uc.edu

My long-term research interests involve the development of a comprehensive understanding of endogenous oscillators, such as the circadian clock, in the control of physiological and behavioral processes in mammals. My academic training and research experience to date have provided me with an excellent background in molecular biology, genomics, and bioinformatics. Before coming to Cincinnati, I was a research assistant in the laboratory of Dr. Axel Hillmer at the Genome Institute of Singapore (GIS). I was part of the team working on elucidating heterogeneity of EGFR mutant lung adenocarcinoma in non-smoking patients. Here, I have built my expertise in developed multiple pipelines to analyze genome-wide data. Our works revealed the complex genomic landscape in Asian EGFR-mutant lung adenocarcinoma, including early dominant driver, high genomic instability, and low background mutation rates. Over the course of my rotation in the Özbudak lab during my first year of graduate study, I have applied my computational expertise to help in extending the analysis algorithms in calculating segmentation noise. As a graduate student in the Hogenesch lab, I have participated in developing an algorithm to identify the spontaneous mutation allele which leads to an extreme short phenotype in hamster. Also, I am involved in studying cell-level alteration under hypoxia in sleep apnea mouse models using single-cell approaches. For my PhD thesis, I am planning to work on developing a machine learning model to identify key factors that drive sleep disorders. I would like to define the most prevalent factors correlated to sleep disorders and pinpoint potential genes that drive the key pathways involving sleep disorders.

Publications, Complete List at PubMed

Year in Program: 3rd

Hometown: Cincinnati, Ohio

Mentors: Drs. Heiny and Landero

Email: normanne@mail.uc.edu

I am interested in the secondary transport of ions using the Na+,K+-ATPase-established gradient in skeletal muscle tissue.

Publications, Complete List at PubMed

Year in Program: 3rd

Hometown: Wooster, Ohio

Mentor: Dr. Zhang

Email: parkecp@mail.uc.edu

I am primarily interested in Quantitative Systems Pharmacology (QSP) modeling and am currently looking into blood coagulation, hemophilia, and treatments. This modeling is primarily done with systems of differential equations, and I am most proficient at doing it in Python, though MATLAB or other languages can be used. Currently I am rotating in biomedical informatics, hopefully gaining more experience with deep learning or statistical programming techniques.

Year in Program: 3rd

Hometown: Lima, Ohio

Mentor: Dr. Miraldi

Email: rizvifw@mail.uc.edu

While completing my Masters degree in Biomathematics at Ohio State University, I had the opportunity to take many interesting classes. One of these was Biomedical Informatics, taught by Dr. Kevin Coombes. In this course, I was really fascinated with the use of various data analysis techniques on biological data, such as Hierarchical Agglomerative Clustering and K-Means Clustering. In class, we used Hierarchical Clustering and Principal Component Analysis on RNA-Seq data of patients with prostate cancer. The data analysis showed that the data set was skewed and confounded by the chip type used. This result was not evident in the initial analysis of the data. Such analysis techniques have been essential in my Masters thesis project on sleep inertia in children. A research paper by Van Dongen et al. [1] finds that sleep-deprived patients can be divided into groups. These groups consist of patients who are found to be resilient, vulnerable, or somewhere in between to sleep deprivation. My Masters thesis advisor, Dr. Best, and I used these machine learning algorithms to evaluate data from a 10-minute visual psychomotor vigilance task test on children aged 5 to 12 to find an example of this characteristic. Further, we would like to generate a model which will be able to use baseline reaction times to predict reaction times of patients awakened from deep sleep (as could happen in the case of a fire alarm). As I graduated and moved on from Ohio State, my interest in machine learning and data analysis led me to the join the Miraldi Lab at Cincinnati Children's Hospital as a first-year student in the Systems Biology and Physiology PhD program at UC. In Dr. Miraldi's lab we use bioinformatics tools to help devise mathematical models to predict transcription factor activity, among other things. Dr. Miraldi and her colleagues were able to create the Inferelator in Th17 cells and predict transcription factor activity using sc-RNA-Seq data. A key input to the Inferelator is the prior matrix. This consists of known transcription factor and gene interactions which the program uses to help prune and predict new edges in the network. In my first semester in Dr. Miraldi's lab I helped generate a prior based on ChIP-seq experimental data available from Dr. Matt Weirauch's lab. With these, nearly 24,000 ChIP-seq experiments, we hope that the Inferelator will be able to perform at a much higher level (in regard to precision vs. recall). Even with much smaller data sets, the Inferelator is able to outperform current state-of-the-art techniques, so a larger data set should provide better precsion vs. recall curves. Moving forward, we hope to create a Convolutional Neural Network (CNN) that uses (sc)ATAC-seq data to predict ChIP-seq profiles. We are interested in using (sc)ATAC-seq as it requires significantly fewer cells than ChIP-seq.

[1] Van Dongen, H.P.A., Baynard, M.D., Maislin, G., and Dinges, D.F., Systematic Interindividual Differences in Neurobehavioral Impairment from Sleep Loss: Evidence of Trait-Like Differential Vulnerability, SLEEP 27.3 (2004), 423-433.

Year in Program: 4th

Hometown: Cincinnati, Ohio

Mentor: Dr. Mackenzie

Email: ruweta@mail.uc.edu

Peter K. Lauf Award 2016, Ohio Physiological Society
Student Research Excellence Award 2017, East-to-West Iron Club
Local Organizing Committee 2018, Ohio Physiological Society
Graduate Student Research Forum 2018, 3rd Place, UC College of Medicine
Research Recognition Award 2019, East-to-West Iron Club

My research is focused on iron transport and homeostasis. I am primarilyinvolved in characterizing the cellular iron exporter ferroportin (Fpn).Expressed in enterocytes, macrophages, and hepatocytes, Fpn is essential forintestinal iron absorption, iron recycling from senescent red blood cells,and stored iron release during times of low iron intake. Fpn is regulatedpost-translationally by the hormone hepcidin, which inhibits Fpn-mediatediron efflux, thereby sequestering iron within cells and reducing its accessto the blood; this regulation is known as the hepcidin/Fpn axis. Therefore,genetic alterations in either hepcidin or Fpn can produce iron pathologiesincluding iron-refractory iron deficiency anemia (as in classical Fpndisease) and iron overload (as in hereditary hemochromatosis).

Despite its importance to systemic iron homeostasis, the thermodynamicdriving force for Fpn-mediated iron efflux remains unknown. I have expressedFpn in RNA-injected Xenopus oocytes and found that calcium activates Fpn-mediatediron transport, but that calcium is not a transported substrate ofFpn. This raises the possibility that Fpn activity could be limited inconditions of hypocalcemia. I continue to examine the molecular physiology ofFpn in the oocyte model and explore potential therapeutic targets for thetreatment of iron disorders.

Publications, Complete List at PubMed

Year in Program: 2nd

Hometown: Cincinnati, Ohio

Mentor: Dr. Crone

Email: schottkm@mail.uc.edu

Year in Program: 5th

Hometown: Cincinnati, Ohio

Mentor: Dr. Tranter

Email:
slonesf@mail.uc.edu

American Heart Association Predoctoral Fellowship

My long-term research interest involves a comprehensive understanding and elucidation of key pathways, transcription/translation modifications, and the complex protein interactions involving cardiomyocytes in cardiac pathology, with the ultimate goal of contributing to the development of a therapeutic treatment for cardiovascular disease. My thesis focuses specifically on increasing our understanding of the underlying molecular mechanisms of the RNA binding protein Human Antigen R (HuR) in modulating the innate immune response following cardiac ischemia/reperfusion (I/R) injury, and on identifying the therapeutic potential of HuR inhibition to preserve cardiomyocyte survival post-reperfusion. While cardiac expression of HuR has been shown to be increased within three days post-I/R and play a role in post-Infarct remodeling, the role of HuR in cardiomyocyte survival following I/R injury is poorly understood and therefore needs to be addressed. Recent findings have suggested that HuR modulates/stabilizes inflammatory factors such as IL-6, TNF-alpha, IL-B and others during I/R both in vivo and in vitro. Therefore, I am interested in HuR's role in modulating pro-inflammatory cytokines and chemokines post-I/R and the effects of inhibiting HuR via a cardiomyocyte-specific knockout or a novel small molecule inhibitor cell on cardiomyocyte survival and thus cardiac remodeling and function. In addition, I would like to pursue HuR's involvement in mediating macrophage/neutrophil infiltration to the myocardium post-I/R.

Publications, Complete List at PubMed

Year in Program: 2nd

Hometown: Rajkot, Gujarat, India

Mentor: Dr. Salomonis

Email: thakkakk@mail.uc.edu

Year in Program: 3rd

Hometown: Kathmandu, Nepal

Mentor: Dr. Crone

Email: thapaca@mail.uc.edu

Damage to the spinal cord can be caused in many ways ranging from motor vehicle accidents to recreational activities. Statistics provided by the National Spinal Cord Injury Statistical Center show that, as of 2015, about 12,500 new spinal cord injuries occur each year. According to the National Spinal Cord Injury Association, 8 of every 95 patients with complete spinal cord injuries above C3 die before receiving any medical treatment. The patients who survive are forever dependent on mechanical respirators to breathe. These statistics underscore the importance of research in spinal cord injury. Currently my research focus is in V2a interneurons. V2a are glutamatergic interneurons that are located within the ventral horn of the spinal cord and are found at all spinal levels. These interneurons are shown to be important for locomotion and breathing. A previous study in our lab showed that after C2 hemi-section, increasing the excitability of V2a neurons restored the activity of previously paralyzed diaphragm. This result substantiates the hypothesis that increasing the activity of V2a neurons may help in restoration of function after spinal cord injury. Similarly, another work in our lab revealed that increasing the activity of V2a neurons results in an increase in activity of auxiliary respiratory muscles (ARMs). However, silencing the activity of V2a neurons also leads to an increase in the activity of ARMs. These experiments showed that there are at least two types of V2a neurons: excitatory V2a neurons and inhibitory V2a neurons. To corroborate this finding, a recently published paper by Hayashi et.al. revealed 11 molecular distinct sub-groups of V2a neurons. Keeping these studies in mind, we are working on identifying expression of different molecules of V2a neurons that may help in identifying different types of V2a neurons.

Year in Program: 6th

Hometown: West Chester, Ohio

Mentor: Dr. Ratner

Email:
thomsocs@mail.uc.edu

The discovery of WNT signaling dates back to the 1970s, yet it is still a growing field of study. Recently, thanks to sequencing technologies, we have identified numerous WNT ligands and receptors but have only recently been able to test their function on a molecular level in cell cultures and in vivo systems.  The complexity of this particular signaling system in biological settings intrigues me to continue dissecting the intricate processes that have yet to be unraveled in cellular systems. Although my graduate career focuses on the role of this molecular signaling system in malignant nerve cancer, I have maintained an interest in neuropharmacology, technology, and basic neurophysiology. Cancer research has been an indispensable avenue for gaining knowledge required in molecular, cellular, and histological systems that is translational to many biological systems in medicine. A general knowledge in cellular and systems physiology, molecular pharmacology, and neuroscience has given me an upper hand in pursuing a career as a Medical Science Liaison. My interest will remain in neuroscience and the understanding and development of new medicine that may have a future impact on public health and technology.

Publications, Complete List at PubMed