A sample of the SMART Program Project Descriptions are listed below in alphabetical order by last name. Projects may vary and are subject to change. An expanded and updated list of the SMART Program mentors and projects will be available at a later date.
Asojo, Oluwatoyin - Structural and functional studies of Medically important proteins. The student will learn how to purify and crystallize proteins that are being investigated as therapeutics targets or vaccine candidates for cancer and infectious diseases. Many of these proteins are vaccine candidates for Neglected tropical diseases (NTDs), which affect the bottom billion and keep them in poverty, and there is a need for new approaches for control
Baker, Mathew - Structure and function of nanomachines. At the NCMI, we employ electron cryo-microscopy and computational biology to visualize and model the complex structures of biological nanomachines. The student will be involved in several aspects of structure determination and analysis of a variety of specimens, from small protein complexes to whole cells. Additionally, there is an opportunity for the student to learn novel protein structure modeling techniques and develop software for the 3D visualization and analysis of these complexes.
Bates, David - Molecular mechanisms of chromosome cohesion in E. coli. We recently showed that after DNA replication, sister chromosomes are physically joined along homologous sequences, analogous to chromosome cohesion in eukaryotes. Interested students will examine two candidate genes for their role in establishing and maintaining chromosome cohesion using a novel cohesion assay, and will map the binding pattern of candidate proteins to the chromosome by chromatin immunoprecipitation and array comparative genome hybridization (ChIP-chip).
Beaumier, Coreen - Our goal is to develop a Luminex®- based multiplex dengue diagnostic kit that can measure all serotypes of dengue, is high throughput, direct, and quantitative. The objective of this proposal is to create a prototype kit and test its specificity and sensitivity in both in vitro and ex vivo samples. Our hypothesis is that such a diagnostic tool will fill in the gaps present in the current available methods for dengue diagnosis
Beeton, Christine - Ion channels in the immune system; targets for the treatment of inflammatory diseases. We investigate the phenotype and functions of ion channels expressed on cells involved in inflammatory diseases such as asthma and rheumatoid arthritis with the goal of developing new treatments for these diseases. Our projects combine techniques in cell biology, electrophysiology, and biochemistry and we use both samples from patients and animal models.
Bondy, Melissa- Breast cancer delay and diagnosis. Research objective: Compare the time to diagnosis and the time to begin treatment of patients with breast carcinoma treated at private and public hospitals of Brazil and USA with survival.
Boriek, Aladin - Remodeling of the respiratory pump in COPD, muscle mechanics, computational mechanics of the respiratory system, rib cage mechanics, mechanotransduction of the diaphragm, membrane mechanics, finite element modeling, quantitative analysis of membrane shape, CT imaging analysis.
Botas, Juan - Identification of potential therapeutic targets of neurodegenerative disorders (ataxias, Huntington’s and Alzheimer's) using a genetic approach in model systems.
Burrin, Doug - Prevention and Nutritional Support of Pediatric GI and Liver Disease. The aim of the project is to investigate the role of parenteral and enteral nutrition on the development of necrotizing enterocolitis and liver disease using a premature piglet model. The student will be involved in animal studies, surgical procedures, laboratory analysis of specimens using histopathology, RT-PCR, western blotting, and biochemical assays. The student will be expected to conduct literature review of the topic, attend clinical conferences and become familiar with general concepts of pediatric gastroenterology, nutrition and disease. Student will also be expected to summarize and analyze results, present oral and written reports to the lab, and finally prepare a oral Power Point presentation of the project.
Chan, Keith - Involvement of stem/progenitor cells in respond to injury and chemotherapeutics.
Chan, Lawrence - We are seeking students who are interested in working hard and learning new lab techniques in projects related to diabetes and curing diabetes with gene medicine approaches.
Chang, Eric - Using yeast genetics to study localization of Ras GTPase. We plan to use standard yeast genetics to knock out a few genes that may regulate subcellular localization of Ras proteins. The gene knock out experiments will be performed using a PCR based method. Expression and localization of Ras will be examined by Western blots and microscopy, respectively.
Corry, David - Fungal pathogenesis of allergic asthma.
Dang, Weiwei - Detecting age-associated intragenic cryptic transcription by TL-seq. Epigenetic changes are not only a hallmark of aging, but also a causal factor for aging in several model organisms. Recently through a high throughput longevity screen, we identified that H3K36 methylation promotes longevity by suppressing age-associated intragenic cryptic transcription. Although the presence of such aberrant transcripts can be detected by the regular RNA-seq method, the precise cryptic initiation sites, and hence the outcome of such transcripts, remain elusive. The goal of this project is to use recently developed transcript leader sequencing (TL-seq) method to precisely determine and quantify age-associated intragenic cryptic transcription.
Fiorotto, Marta - An inadequate diet during critical stages can permanently alter skeletal muscle mass and composition. The goal of the project is to evaluate if the capacity if muscle to repair itself following an injury is altered. The project will involve the analysis of skeletal muscle rates of protein synthesis in adult mice that have been subjected to undernutrition during development following an injury.
Graham, Brett - Genetic Screen for Suppressors of Mitochondrial Mutant Phenotypes in Drosophila Mitochondrial disease is an important cause of brain-muscle dysfunction and results from defects in oxidative phosphorylation and metabolism. The student will participate in a project to perform a genetic screen in the fruit fly designed to identify suppressors of abnormal eye development caused by mitochondrial dysfunction. The student will learn how to handle flies, recognize abnormal phenotypes, and design/execute genetic crosses and analyses.
Hadsell, Darryl - Developmental changes in the mammary transcriptome of the lactating mouse. The student will use select software packages to analyze and summarize micro-array data that have been collected for mammary tissue RNA or the lactating mouse at 6 time-points during the cycle. Some of the genes identified as different will be reanalyzed by quantitative real-time RT-PCR. The student will also be given the opportunity to write up the work in a manuscript.
Hirschi, Kendal - My research focuses on the nutritional improvement of plants and bridging the gap between plant biology and nutritional sciences. I work on the basic mechanisms of plant gene regulation and transport while trying to create rationale strategies for the nutritional enhancement of crops. We try to address how changes in plant architecture alter nutrient bioavailability. Generations of nutritional scientists have cataloged the nutrients in foods, while in the last decade plant genome projects have facilitated the development of genetic tools to manipulate nutrient content; however, few studies have assessed the impact that these genetic modifications have on nutrient bioavailability. In summary, we are making more nutritious foods to try to alleviate world hunger problems.
Jacot, Jeffrey - Tissue Engineering of a Biological Septal Patch. Septal heart defects are the most common type of congenital heart defect. Surgical closure with an acellular patch results in an increased likelihood of asynchronous contraction, arrhythmia and fibrillation. Our lab aims to develop a cellular, biofunctional septal patch with mechanical and conductive properties equivalent to native tissue. This student will choose from projects involving the design and testing of biomaterial scaffolds for a septal patch, the evaluation of the electrophysiology and force generation of engineered tissue, or the culture and evaluation of progenitor cells for use in cellular septal patches.
Jankowsky, Joanna - Making new cells in an old brain. Our group is interested in understanding how specialized parts of the adult brain retain the capacity to make new neurons throughout life, and how the production of adultborn neurons is compromised by diseases of aging such as Alzheimer’s dementia. We have show that the long-term survival of newborn neurons in one of these specialized regions is severely reduced in transgenic mice with Alzheimer’s-like lesions in the brains. We are now working to identify precisely when the newborn neurons are most susceptible, and to examine their morphology at this time point so that we might hone in on the cause for increased mortality in this fragile population of aspiring neurons.
Kaipparettu, Benny - Role of mitochondria in cancer progression.
Lacorazza, Daniel - Role of a tumor suppressor in immune cell signalings. We study the transcriptional control of hematopoiesis and development of the immune system, particularly on genes that control cellular quiescence in hematopoietic stem cells and naive T cells. We recently identified a tumor suppressor that inhibits T cell proliferation downstream of T-cell receptor signaling. We are currently studying the impact of this negative regulation on immune response, immunological memory, and leukemogenesis.
Lamb, Dolores - 1) Enhancement of Vitamin D Action in Advance Prostate Cancer Through CYP24 Silencing. 2) Improving the Diagnosis of Congenital Genitourinary Defects. 3) Miscoassisted Fertilization and Genetic Defects in Male Infertility. 4) Leptin-Ghrelin Interplay in the Testis.
Larina, Irina - Revealing early embryonic cardiovascular development through live imaging.
Li, Yi - Breast cancer stem cells. Too often breast cancer treatment are ineffective, because of current therapeutics do not target cancer stem cells. We have already isolated breast cancer stem cells from a unique mouse model. A summer student will join our team to further purify and characterize these cancer stem cells, to study their unique molecular network, and to attempt to treat them with approaches including nanotechnology, immunotherapy, and gene therapy.
Lopez-Terrada, Dolores - Biology of pediatric tumors of the liver (hepatoblastoma).
Mardon, Graeme - Genome-wide identification and functional analysis of Drosophila retinal determination genes.
Mendoza, Daniel - Immune responses to pneumococcal vaccines in healthy and HIV-infected subjects
Morrisett, Joel - Visualization and Quantitation of Proteins involved in Development of Atherosclerotic Plaques & Cardiovascular Disease. MRI 2D Images of carotid endarterectomy tissues are acquired then used to construct 3 D models. Tissues are cut into small sections which are stained with labeled antibodies specific for different marker proteins. The location and intensity of label fluorescence is mapped onto the 3D model, allowing comparison of the location of the atherosclerotic plaques and proteins which may mediate plaque formation. Our ultimate goal is to identify and eliminate the culprit proteins causing the disease.
Neilson, Joel- Post-Transcriptional Control of Gene Expression in Hallmarks of Human Cancer. The current research focus of the Neilson laboratory is on identifying novel genetic circuits underlying human cancer that are invisible in transcriptional profiling datasets. We have successfully identified such a circuit in the context of epithelial-mesenchymal transition in breast epithelial cells, and are now gearing up to apply our methodologies to other aspects of human cancer, such as drug resistance and the DNA damage response. Based on a given student's interest, subprojects within our overall goal might include bioinformatics, validation of primary data by qRT-PCR, immunoblot, and reporter assay, and functional RNAi/overexpression experiments in the context of cell culture.
Nguyen, Hoang - Skin epithelial stem cell maintenance and cell fate specification. The student’s project will focus on a few candidate genes that control stem cell fate in the skin. The project will include characterizing the expression pattern of the candidate genes by performing in situ hybridization and immunofluorescence. The student will employ molecular biology to express the genes of interest in expression vectors and use cell culture to test the function of the genes on skin stem cell proliferation and differentiation.
O’Malley, Bert - Hormones in human health and disease. The lab studies the roles and mechanisms of hormone action, particularly in gene regulation. A number of projects are available that are applicable to cancer.
Overbeek, Paul -Lentiviral Gene Therapy. Recombinant lentiviruses provide promising tools for gene therapy for inherited genetic disorders. We use mouse models for human genetic disease. In our initial experiments, we used a lentivirus to achieve efficient and effective germ-line therapy for albinism. The genetic rescue was stable and transmitted thru the germline, providing long term rescue for the genetic disorder. The summer student(s) will design lentiviral vectors to do gene therapy for other inherited disorder that cause ocular, craniofacial, epidermal and/or mental deficiencies.
Pati, Debananda - Mitotic regulation and cancer. My laboratory is performing research in two main areas: 1) investigation of the molecular basis on aneuploidy in breast cancer models, and 2) mitotic regulation of apoptosis in leukemia. We have identified a set of chromosomal segregation proteins that coordinate aneuploidy, cell division, and apoptosis in cancer tissues in an effort to understand the regulatory network that assures accuracy of chromosomal separation in dividing cells. Our research is aimed at elucidation the molecular mechanism of chromosomal instability through analysis of the factors that mediate sister chromatid cohesion and separation during mitosis. We have recently proposed a new handcuff model for the chromosomal cohesion complex, and have also demonstrated that overexpression of Separase, the cohesion protease that cleaves cohesion subunit Rad21 during mitosis, causes aneuploidy and tumorigenesis. The current focus in my lab is 1) the structural and functional analysis of the cohesion complex, 2) regulation of Separase expression and aneuploidy by p53 and steroid hormones, using Separase transgenic mice models 3) designing and screening small molecular inhibitors against Separase enzyme active site and testing efficacy for tumor regression using our recently developed Separase inducible mouse mammary tumor model, and 4) identification and characterization of a novel nuclear protease that cleaves cohesion Rad21 for apoptosis induction.
Pautler, Robia - The role of GMS gangliosidosis in the development of Alzheimer’s disease pathology.
Poche, Ross- Characterization of a novel mouse model affecting brain development. We have generated a point mutation that mimics the same mutation observed in human patients with a previously unknown neurodevelopment disease. The SMART student project will involve phenotypic characterization of this mouse line so that we may better understand the pathophysiology is this new human syndrome.
Prasad, B.V.V. - Structural basis of strain-dependent glycan recognition in gastroenteric viruses such as rotaviruses and noroviruses. A critical event in the life cycle of a virus is its initial attachment to host cells. This involves recognition by the viruses of specific receptors on the cell surface, including glycans. Viruses typically exhibit strain-dependent variations in recognizing specific glycan receptors, a feature that contributes significantly to cell tropism, host specificity, host adaptation and interspecies transmission. Examples include influenza viruses, noroviruses, rotaviruses, and parvoviruses. Both rotaviruses and noroviruses are well known gastroenteric pathogens that are of significant global health concern. While rotaviruses, in the family Reoviridae, are the major causative agents of life-threatening diarrhea in children, noroviruses, which belong to Caliciviridae family, cause epidemic and sporadic cases of acute gastroenteritis across all age groups. Both exhibit enormous genotypic and serotypic diversity. Consistent with this diversity each exhibits strain-dependent variations in the types of glycans they recognize for cell attachment. This project involves understanding the structural basis of glycan specificity in rotaviruses and noroviruses using a combination of X-ray crystallography, biochemical and virology techniques. The ultimate goal is to use this information to design potent antiviral drugs for these viruses.
Rasband, Matthew- The functional organization of axons in health and disease.
Smith, C. Wayne -Inflammatory aspects of obesity. The project involves investigation of the inflammatory aspects of obesity in an animal model, mice fed a defined high fat diet. Within days of beginning a high fat diet, aspects of the innate immune system in adipose tissues become activated and there is progressive infiltration of the fat tissues with leukocytes, increased production of inflammatory cytokines and chemokines, and developing low grade systemic inflammation. The student will participate with the research team working on this project in the investigation of specific leukocyte subsets, inflammatory mediators on anti-inflammatory factors.
Trautner, Barbara - Preventing catheter-association infection. My laboratory studies prevention of catheter-associated urinary tract infection through bacterial interference. We are interested in genetic manipulation of E. coli to create a benign, protective biofilm on urinary catheters that discourages catheter colonization by pathogens. A student involved in this project would set up bacterial adherence experiments on various modified surfaces. The student would also be involved in imaging the adherent organisms using microscopy. The student could participate in cloning various biofilm genes as well as studying gene expression through QRTPCR.
Van den Veyver, Ignatia - Mouse Models of human disease. We identified that PORCN, a gene on the X-chromosome encoding the human homologue of the Drosophila Porcupine protein is mutated in patients with Goltz syndrome or Focal Dermal Hypoplasia (FDH), a rare developmental disorder. FDH is a rare disorder with multiple abnormalities involving primarily skin, bones of fingers and toes, teeth and eyes. Porcn in mouse and Porcupine in Drosophila are endoplasmic reticulum (ER) transmembrane proteins that lipid-modify WNT proteins, which is thought to be essential for their secretion and normal WNT signaling. We are currently generating mouse models with conditional inactivating mutations in Porcn. The student will participate in characterization of the mice. In addition we are studying the effect of various mutation s in cell culture assays, which the student can also participate in. The student will work under supervision of an experience postdoctoral researcher.
Wang, Qinghua - Elucidation of molecular mechanisms of cancer initiation and polycomb-mediated epigenetic regulation. Description: In our group, we are using a wide array of techniques with the ultimate goals of elucidating the molecular mechanisms underlying cancer initiation and polycomb-mediated epigenetic regulation.
Wehrens, Xander - Molecular basis of heart failure. Student will be involved in translational studies into the molecular basis of heart failure and sudden cardiac death. The mentor’s lab has generated several mouse models with genetic mutations in calcium channel-associated proteins, found in patients with heart failure. Student will be involved in studying the effects of abnormal calcium cycling via these proteins on the structure and function of the mouse heart and hear muscle cells, using a variety of techniques (biochemistry, electrophysiology, imaging).
Zechiedrich, Lynn - 1. Combat antibiotic resistance. We take a multipronged, multidisciplinary approach to: A) identify new antibiotics that work against drug-resistant pathogens B) uncover new antibiotic targets C) understand how antibiotic resistance develops D) take a systems approach to understand how the patient influences antibiotic treatment outcomes and antibiotic resistance. 2. Develop novel non-viral gene therapy delivery vectors. We study tiny circles of DNA for gene therapy. These are the only gene delivery vectors that survive aerosolization and human blood. We work to optimize how to deliver these vectors to the lungs to treat various important human diseases. 3. Understand the mechanism of anticancer drugs. We are working to understand how anticancer drugs work. We uniquely study physiologically relevant DNA, drug target topoisomerases, and drugs.