University Honors ProgramUniversity of Cincinnati

University Honors Program

Biomedical Research Mentoring Program - Spring 2014 Projects

APPLICATIONS ARE NOW CLOSED!

Fall 2013 Instructions for Applicants

STEP 1: Applications are due to individual mentors (via email) no later than Friday, November 8th, 2013. An application consists of a resume or CV and a cover letter of interest (be sure to address why are you interested in their specific research project). Application materials for a project should be attached to one email with the subject: "Biomedical Research Mentoring Program Application."

In your letter of interest, please be sure to indicate whether or not, given your current obligations/plans, you would be able to continue the research experience throughout the 2014 summer.

STEP 2: After emailing applications to mentors, all applicants should complete this form to notify the University Honors Program of the projects to which they have applied.

Questions about projects should be directed to the mentors. Do not contact the PIs (however, PI websites might provide a valuable big-picture overview of research).

All University Honors students are eligible; first- and second-year students are especially encouraged to apply.

Students will be directly contacted by mentors regarding any interview processes.

Age-related changes in immune cells in rat models of Parkinson's disease

Mentor: Sarah Cassella (Graduate Student)
PI: Kim Seroogy, PhD
Department: Neurology
Email: casselsh@mail.uc.edu
Location: CARE, UCCOM

One percent of the American population at the age of 65 is diagnosed with Parkinson’s disease (PD), making age the highest risk factor for developing the disease.  In addition to the hallmark features of PD, microglia (the immune cells of the nervous system) are increased in number and activation state in PD brains. This observation suggests a non-cell autonomous role of microglia in PD etiology and/or progression. Our lab has observed a significant increase in microglial cells in the brains of aged rats, and is about to begin projects to examine the influence of specific proteins on these changes. 

An honors student interested in this topic will work with a senior level graduate student to investigate the role of microglia in rat models of PD. Projects involve rat brain surgery, behavior testing, and analysis of proteins via immunohistochemistry and western blotting.

Autism, Angelman, and Fragile X Syndrome: Targeted Treatment Approaches using Mouse Models

Mentor: Tori Schaefer, PhD (Research Associate)
PI: Craig Erickson, MD
Division: Child Psychiatry, CCHMC
Email: tori.schaefer@cchmc.org
Location: 3430 Burnet Ave Building, CCHMC

Our group runs the Angelman and Fragile X Syndrome Clinics and the Developmental Disabilities Translational Animal Research Lab.  Angelman Syndrome (AS) is a rare genetic disorder characterized by developmental and motoric delays.  Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and a common single gene cause of autism.  In the translational animal lab, we use several mouse models of FXS and AS to better understand the pathophysiology of these disorders and to identify potential pharmacotherapy targets and biomarkers of treatment response.  Once targets are identified, we treat FXS mice with drugs and determine if behavioral and neuronal deficits can be rescued.  We are also interested in the early neuronal changes induced by these syndromes and how they affect behavior.  This work contributes directly to future clinical trials in FXS and AS by identifying potential drug targets for treatment and serving as an initial indication of a drug’s efficacy and safety.

The prospective student’s interests will greatly influence the type of techniques they will learn and may involve animal behavior, neurochemistry, electrophysiology, and immunohistochemistry.  The student will learn skills important for biomedical research which may include:  animal handling, rodent behavioral techniques and analysis, genotyping, agarose gel electrophoresis, protein analysis, immunostaining, or microscopy.  There may also be opportunities for the student to meet and observe patients with AS and FXS in our clinic to better facilitate their understanding of translational research.

Bone Marrow Failure in Fanconi Anemia

Mentor: Tingting Zhang, PhD (Postdoctoral Fellow)
PI: Qishen Pang, PhD
Division: Hematology & Cancer Biology
Email: ting.ting.zhang@cchmc.org
Location: Building S, CCHMC

Fanconi anemia (FA) is an inherited recessive syndrome, characterized by high cancer incidence and progressive fatal bone marrow failure. Sixteen FA proteins are required for the DNA repair pathway. FAAP20 is a newly identified FA-associated protein, which has been shown to regulate the FA core complex.

Work in this project focuses on studying the cause of bone marrow failure in Fanconi with the new Faap20 knockout mouse model. Faap20 deficiency causes reduced hematopoietic progenitor repopulation ability in irradiated recipients. Consistent with clinical phenotype of FA patients, the Faap20-/- mice subjected to chemotherapy reagent MMC succumb to bone marrow failure associated with defect in the hematopoietic stem cell (HSC) population. Taken together, our data demonstrate that FAAP20 plays an important role in hematopoiesis, probably through its function in HSC maintenance. We are now further exploring the mechanism involved with the HSC defect caused by the Fanconi complex protein mutation.

An honors student interested in this project will work in a big lab with several other research fellows. Projects are dependent on individual student interest, but will mainly involve PCR, animal work or cell culture.          

Finding a Bio-marker for Reading Disability (Dyslexia) - a Neuroimaging Study using fMRI

Mentors: Tzipi Horowitz-Kraus, PhD (Postdoctoral Fellow)
PI: Scott Holland, PhD
Division: Pediatric Neuroimaging Research Consortium and Communication Sciences Research Center, CCHMC
Email: Tzipi.Horowitz-Kraus@cchmc.org
Location: Building S, CCHMC

It is well known that individuals with reading disability (or Dyslexia) suffer from slow and inaccurate reading. What is less known is that these individuals also share deficits in other domains (e.g., memory, inhibition, speed of processing, etc.). Reading disability is currently diagnosed based on behavioral testing, teachers’ reports and questionnaires. This approach is problematic since it is not objective or sensitive to the deficit’s severity and might results in an inaccurate diagnosis.

In this clinical study, we aim to find a bio-marker that will help to objectively differentiate children with reading disabilities from typical readers. For this purpose we are using a neuropsychological battery and anatomical and functional data form functional magnetic resonance imaging (fMRI). 

Students will be able to take part in a neuroimaging study, including assessing the children for their reading and cognitive abilities and collecting the imaging data. They will also participate in behavioral and imaging data analyses.

Generating a Dek Transgenic Mouse Model for Studies of Head and Neck Cancer

Mentor: Marie Matrka (Graduate Student)
PI: Susanne Wells, PhD
Department/Division: CCHMC Hematology/Oncology
Email: matrka@hotmail.com (preferred) or marie.matrka@cchmc.org
Location: Building S, CCHMC

Head and neck cancer (HNC) is the sixth most common malignancy worldwide with a 40% five year survival rate. It is typically caused by smoking and drinking or infection with the human papilloma virus (HPV). Treatment often leads to irreparable facial disfiguration and loss of the ability to speak, chew or swallow. Therefore, we are investigating new therapeutic targets such as the DEK oncogene.

DEK is a nuclear protein overexpressed in HNC whose expression drives cell growth and loss leads to cell death. We are generating Dek transgenic mice to determine if Dek causes tumor growth and investigate its therapeutic potential.

The student will genotype mice to screen for the presence of the Dek transgene utilizing lab techniques such as DNA isolation, polymerase chain reaction, and gel electrophoresis. He or she will work closely with a graduate student to understand the goals of the project, learn proper laboratory technique, and present their work at monthly lab meetings.

How are neurons formed in the developing embryonic brain?

Mentor: Kaushik Roychoudhury, PhD (Postdoctoral Fellow)
PI: Kenneth Campbell, PhD
Division: Developmental Biology
Email: Kaushik.Roychoudhury@cchmc.org
Location: Building S, CCHMC

The brain is a very complex organ composed of millions of nerve cells (neurons) and glia. Brain development starts in early stages of the embryo, long before birth. The mammalian brain is broadly divided into the forebrain, midbrain and hindbrain. The forebrain is responsible for learning, memory, olfaction, motor and sensory functions. Many of the neurons of the forebrain originate from neural stem and progenitor cells that reside in the ventral part of the embryonic forebrain. We still do not understand the mechanisms behind how these stem/progenitor cells ultimately create the complex network of the forebrain and how a stem cell-progenitor pool is maintained in an undifferentiated stage. For the past two years, I have been trying to piece together the molecular mechanisms behind these processes. These include the phosphorylation of transcription factor molecules, protein-protein interactions and protein-DNA binding.

I use many molecular and genetic techniques in my research, including molecular cloning and creating mutant versions of transcription factors, creating and studying transgenic animals, luciferase reporter assays, yeast two and three hybrid studies, recombinant protein expression and purification, PCR,  etc. and use these techniques figure out how neurons are formed and how the brain is constructed in the developing embryo.

The interested student could participate in one of several distinct projects, based on their interests including: 1. Characterizing a phospho-mutant transgenic mouse line 2. Studying protein-DNA binding in a cell culture based system or 3. Characterizing a novel binding partner of the transcription factor Gsx2. These projects will involve one or more of the following: Molecular cloning, tissue culture, western blotting, histology and Immunohistochemistry.

Investigating Cytokine Signaling Pathways in Severe Asthma

Mentor: Sara Stoffers (Graduate Student)
PI: Ian Lewkowich, PhD
Department/Division: Pediatrics/Immunobiology
Email: sara.stoffers@cchmc.org
Location: Building S, CCHMC

Cytokines are small proteins that serve as messengers between cells. Defects in cytokines and the intracellular signaling pathways that they activate are associated with a wide variety of diseases, including asthma. Our lab investigates molecular pathways activated by two distinct groups of cytokines (Th2, Th17) that may support the development of severe asthma. We have found that Th17 cytokines synergize with Th2 cytokines to increase airway hyperresponsiveness, or asthma “attacks,” in mice; however, the mechanism by which Th17 cytokines do this is currently unknown. As synergy between Th2 and Th17 cytokines also occurs in human cells, we believe that a similar process may operate in severe asthmatics. This research is important because severe asthma remains poorly controlled by conventional therapies (i.e., steroids, inhalers) and comes with a greater risk for hospitalization and death.

An honors student interested in this lab will receive hands-on training in many molecular biology and immunological techniques, including cell culture models of mouse cell lines, ELISA, Western blotting, qRT-PCR, and more. Students will also discuss and interpret their data, as well as relevant reading material, regularly with their mentor.

Molecular Mechanisms of Manganese Neurotoxicity in Rats

Mentor: Robyn Amos-Kroohs (Graduate Student)
PI: Michael Williams, PhD
Division: Neurology (CCHMC)
Email: Robyn.amos-kroohs@cchmc.org
Location: Building R, CCHMC

In children with increased manganese exposure, the resulting toxicity has been associated with decreased IQ, ADHD-like symptoms, and other behavioral and cognitive deficiencies.  This is possibly exacerbated by factors such as low social economic status environments and iron deficiency, the most prevalent nutritional problem in the world.  Previous work in our lab has shown some cognitive and behavioral deficits in a rat model of manganese exposure, including decreased anxiety and increased errors in learning a maze.

I am currently working on creating an animal model that explores those factors that may increase the likelihood of manganese neurotoxicity.  The combination of developmental stress and manganese exposure is thought to produce additive effects.  Iron deficiency is associated with increased manganese deposition in the brain.  Intending to represent a previously published ‘real world’ situation, this model uses developmental stress and iron deficiency to explore the various cognitive and behavioral deficits associated with clinical studies of developmental manganese overexposure.  It will also be used to look at the underlying molecular mechanisms behind these interactions and to explore methods of detecting toxic exposure.  The overall goal of my work is to associate neurobiological defects or malformations with behavioral and cognitive deficits.  This type of project will involve several different aspects, at both the whole animal and molecular levels, including examination of neurotransmitter systems, brain metabolism and mitochondrial function, and animal behavior.  My neurobehavioral assays are over, so the focus has switched to molecular mechanisms behind the cognitive and behavioral deficits.  Current projects are concentrated on electrophysiology work, protein quantification via Western blot, and neurotransmitter quantification via HPLC.

Role of the Honors Student: An Honors student working with me would be learning the fine art of Western blots, which will be used to quantify both metal transport proteins and neurotransmission regulation proteins in the brain and how they’re affected by the model. The student would leave this experience with the ability to prepare, plan, and finish a complete set of experiments, as well as gaining proficiency in data analysis and interpretation. 

Preprocessing Human Brain MRI Images

Mentor: Hailong Li, PhD (Postdoctoral Fellow)
PI: Jason Lu, PhD
Division: Biomedical Informatics
Email: hailong.li@cchmc.org
Location: Building S, CCHMC

Our current research focuses on analysis of human brain images. With the development of modern electromagnetic techniques such as magnetic resonance imaging (MRI), high resolution human brain images can be obtained for brain disease diagnosis. However, it is difficult to identify changes in the early stage of the disease. Therefore, we are combining machine learning algorithms and statistical methods to aid the early diagnosis of brain diseases so that previously unobservable evidence within brain images can be discovered.

To utilize computational analysis on the images, the first step is brain image pre-processing. Due to technical issues, brain images from MRI machine may not be good enough to be analyzed directly. For example, motion of the head may compromise image quality heavily and artifacts would be introduced. So, common image artifacts need to be corrected before further analysis with standardized image processing methods.

In this project, the undergraduate student will be involved in preprocessing images with software SPM in our lab. SPM is a program package, widely used in brain imaging analysis. Common preprocessing steps such as motion correction, image alignment, and segmentation are readily implemented within SPM. Students in this project will learn SPM and perform basic image preprocessing steps, which will pave the way for future brain research. 

Protection against non-alcoholic fatty liver disease

PI and Mentor: Vikram Prasad, PhD (Research Assistant Professor)
Department: Molecular Genetics, Biochemistry and Microbiology
Email: prasadvm@ucmail.uc.edu
Location: Cardiovascular Research Center (CVC) 2960, UCCOM

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the western world. It is closely linked to the rise in obesity and insulin resistance, and is considered a major cardiovascular risk factor. In addition, NAFLD is known to lead to liver cirrhosis and cancer. Therefore, there is an urgent need to identify new therapeutic targets that can limit or reverse the development of this disease. In its earliest stages, NAFLD is associated with lipid accumulation in the liver. We have preliminary evidence that a membrane protein called NHE1 contributes to diet-induced lipid accumulation in the liver. Using (a) genetically-modified mouse models; (b) a high-fat diet regimen for mice; and (c) a variety of biochemical techniques, we will elucidate the role of NHE1 in diet-induced fatty liver disease. The objective is to generate information that will help design more effective therapies against NAFLD.

Upon joining this project an honors student will have the opportunity to learn and carry out experiments that utilize techniques such as tissue-culture of mouse cells, polymerase chain reaction, and immunoblot protein analysis. It is anticipated that the student, after an initial training period, will be able to independently carry out experiments, and offer interpretations of his/her findings.

Roles of the human CST complex in DNA replication

Mentor: Jason Stewart, PhD (Postdoctoral Fellow)
PI: Carolyn Price, PhD
Division: Cancer Biology
Email: jason.stewart@uc.edu
Location: Vontz Building, UCCOM

Our research group is focused on understanding how defects in DNA replication lead to genome instability. Genome instability is defined as genetic alterations that effect normal cellular function. It is one of the hallmarks of cancer initiation and can also lead to a variety of other human diseases.

The aim of the honors student project will be to determine the extent to which a telomere-associated protein complex, CTC1-STN1-TEN1 (CST), promotes DNA replication at chromosomal fragile sites. Fragile sites are DNA regions of the chromosomes that are susceptible to DNA breakage under replication stress and are frequently deleted or translocated in various cancers. Studies suggest that additional proteins are required to replicate the DNA at these sites due to stalling, or blockage, of the normal replication machinery. Recently, our group discovered that CST, a DNA binding protein, helps to rescue stalled DNA replication. We are now interested in determining whether CST is specifically required at difficult-to-replicate chromosomal fragile sites.

To complete this project, the honors student will learn a variety of cell biology, molecular biology and biochemical techniques, including metaphase chromosome spreading, fluorescence microscopy, PCR, western blotting, and human cell culture techniques.

Role of Meis1 transcription factor in pediatric leukemia

Mentor: Jayeeta Roychoudhury, PhD (Postdoctoral Fellow)
PI: Ashish Kumar, PhD
Department/Division: Bone Marrow Transplantation and Immune Deficiency/Cancer and Blood Disease Institute, CCHMC
Email: Jayeeta.Roychoudhury@cchmc.org
Location: Building S, CCHMC

Chromosomal translocations of the MLL gene are frequently found in infant-leukemia. These leukemias, resistant to current therapies, are almost always fatal. MEIS1, a transcription factor, is highly expressed in such types of leukemias. Preliminary experiment showed that MEIS1-deletion led to decreased expression of hepatic leukemia factor (HLF).

The honors student will help to validate the role of HLF in such types of leukemias. To attain the objective, the honors student will evaluate the effect of Meis1-knockdown on HLF in leukemic cells, using techniques like quantitative RT-PCR, genomic PCR and western blot. Our rationale for performing these studies is to develop novel therapies aimed at blocking MEIS1-dependent leukemia.

Role of Semaphorins in Mouse Brain Circuits

Mentor: Zirong Gu (Graduate Student)
PI: Yutaka Yoshida, PhD
Division: Developmental Biology, Cincinnati Children's Hospital
Email: Zirong.Gu@cchmc.org
Location: Building S, CCHMC

Dr. Yoshida’s lab laboratory focuses on corticospinal circuits in mice to investigate the development and regeneration of brain circuits. Corticospinal circuits connect the cerebral cortex with the spinal cord and play essential roles in our voluntary movement. Research in the laboratory explores the formation of these circuits during development and how the organization of these circuits control specific behaviors. We also study how corticospinal circuits response to spinal cord injury with the goal of developing therapies for promoting regeneration. To do so, we utilize mouse genetic and transynaptic tracing virus to monitor and visualize the connectivity of corticospinal circuits during development and regeneration.

My research is focused on Semaphorins, which are a class of secreted and transmembrane proteins that act as axonal growth cone guidance molecules. Specifically, I found one transmembrane Semaphorin is involved in the pruning or developmental degeneration of corticospinal circuits, while secreted Semaphorin functions as a repellent to sculpt the axonal arborization pattern of corticospinal circuits. Future studies are going to utilize transynaptic tracing virus to examine how the connectivity of corticospinal circuits is altered in these Semaphorins mutant mice. Mouse behavioral tests will then be used to assess the functional consequences of miswiring of corticospinal circuits in these mutants.

Prospective students undergoing training under me will gain substantial theoretical knowledge and hands on experience on mouse genetics as well as a number of molecular biology techniques such as neuronal culture, PCR, Immunostaining, fluorescence microscopy etc. Students also can be exposed to more advanced experimental techniques that coincide with their interest, such as animal surgery, transynaptic tracing virus, and behavioral test.

Stem cell extracellular matrix suppresses transplantation rejection

Mentor: Vivien Jane Coulson-Thomas, PhD (Postdoctoral Fellow)
PI: Winston Kao, PhD
Division: Ophthalmology
Email: vivien.coulson-thomas@uc.edu
Location: CARE, UCCOM

We have previously shown that mesenchymal stem cells isolated from human umbilical cords are not rejected when transplanted into the stroma of immunocompetent mice.  Therefore, these human stem cells attain the ability to suppress the mouse immune system thereby avoiding rejection.  We are currently investigating the mechanism by which the stem cells suppress the host immune response.  We have recently isolated a glycosaminoglycan present in the glycocalyx of the stem cells which is responsible for them suppressing the inflammatory response.  Therefore, the aims of the project are to characterize the glycocalyx secreted by UMSC and elucidate the mechanism by which these cells evade host rejection.

An honors student working on this project would choose between elucidating the mechanism by which stem cells suppress the immune system attaining hands-on experience in a vast array of cell biology techniques including primary and established cell line culture, various co-culture techniques, isolation and maintenance of stem cells, immunofluorescence, or characterize the glycocalyx attaining training in structural biology techniques such as protein purification, Western Blotting, high pressure liquid chromatography (HPLC) and immunofluorescence.  If the student is interested both projects would involve animal manipulation and surgery.

Submission and subversion: Role of immune cells in metastatic brain cancer

Mentor: Victor M. Blanco, PhD (Postdoctoral Fellow)
PI: Xiaoyang Qi, PhD
Department/Division: Internal Medicine/Hematology & Oncology
Email: victor.blanco@uc.edu
Location: Vontz Center for Molecular Studies, UCCOM

Metastatic brain tumors are the most common intracranial neoplasm in adults, affecting about 200,000 people in the USA every year. Even after aggressive treatment, median patient survival is just 9 months. Although the immune system is a formidable barrier against cancer, some tumors are able to subdue immune cells and subvert their functions, so that they support tumor growth instead of fighting it. Therefore, identifying the mechanisms that turn immune cells into tumor-supporting cells is critical to design effective cancer therapies.

Work in our lab addresses molecular aspects of tumor physiology and the therapeutic potential of Saposin-C/ dioleoyl-phosphatidylserine (SapC-DOPS) nanovesicles for tumor detection and treatment. Using brain metastasis mouse models, the proposed research focuses on the mechanisms of formation and development of metastatic brain tumors and their interactions with surrounding –stromal- resident brain cells (astrocytes, microglia) and infiltrating immune cells (macrophages, dendritic cells). We seek to characterize these tumor-stromal interactions, how cancer cells dampen the ability of immune cells to kill tumors, and the potential modulatory effects of SapC-DOPS on immune cell functions. Methodologies to be applied to this end include cell culture, in vitro cell assays, and immunohistochemistry of mouse and human brain sections.

Undergraduate Research in Hematopoietic Stem Cell Gene Therapy

Mentor: Mei Dai, PhD (Postdoctoral Fellow)
PI: Dao Pan, PhD
Division: Gene Therapy/Cancer and Blood Disease Institute, CCHMC
Email: mei.dai@cchmc.org
Location: Building S, CCHMC

Mucopolysaccharidosis type I (MPS I), one of the most common lysosomal storage diseases (LSD), is caused by defective Alpha-L-iduronidase (IDUA) and consequent systemic accumulation of the glycosaminoglycans. Clinical features in patients with MPS I include multiple organ defects as well as mental retardation in severely affected patients who would die by the age of 10 without treatment. Clinically available treatment includes bone marrow transplantation (BMT) and enzyme replacement treatment, but none of them have had any major effect on abnormalities in the central nerve system (CNS) or the skeletal system. A potential new treatment, hematopoietic stem cell gene transfer followed by autologous transplantation is an attractive alternative for LSD treatment that could provide lifelong therapeutic effects without the morbidity and mortality of allogeneic transplantation. Our previous results demonstrate that forcing IDUA transgene expression in blood cells of various lineages can produce and release the lysosomal enzyme successfully and continuously at supraphysiological levels in circulation, and achieve phenotypic correction in peripheral organs and the CNS of a mouse model of MPS I.

An undergraduate in this lab will have intensive hands-on training in molecular and cell biology as well as mice genetics including cell culture, virus packaging, genotyping, and mouse work such as bleeding, perfusion. Students will also have instant discussion with their mentor for trouble shooting and data interpretation. This project will help us find the best way to treat MPS I patients.